Professor Eduard Sanders

Research Area: Clinical Epidemiology
Technology Exchange: Vaccine production and evaluation
Scientific Themes: Tropical Medicine & Global Health
Keywords: Acute HIV infection; PrEP; ART; STI/HIV; key populations; MSM
Web Links:

Dr Sanders is a public health physician and epidemiologist affiliated with Oxford University and supported by the International AIDS Vaccine Initiative (IAVI). He initiated the establishment of the District Hospital HIV care and research programme in Kilifi in 2003 and is the principal investigator of several observational studies involving mostly men who have sex with men (MSM) and female sex workers (FSW) in Kilifi and Malindi Districts. His research includes studies of acute HIV infections, HIV-exposed sero-negatives, Pre-Exposure Prophylaxis (PrEP) which are conducted at a satellite KEMRI-clinic in Mtwapa, and Community HIV Centre, in Kilifi. He is an advisor to the Ministry of Health’s working group on ‘Most at Risk Populations’ and his interests include public health interventions to reduce HIV transmission in vulnerable populations; early diagnosis of acute HIV infections and prevention of onward transmission; bacterial STI in high risk populations, and HIV-1 early treatment trials.

Name Department Institution Country
Professor Tomas Hanke Jenner Institute Oxford University, Old Road Campus Research Building United Kingdom
Professor Thumbi Ndung'u UKZN South Africa
Dr Joakim Esbjornsson NDM Oxford University United Kingdom
Professor Tobias Rinke de Wit University of Amsterdam Netherlands
Professor Don Operario Brown University United States
Dr Susan M Graham University of Washington United States
Professor Scott McClelland University of Washington United States
Professor Sarah L Rowland-Jones Target Discovery Institute Oxford University, NDM Research Building United Kingdom
Professor Persephone Borrow NDM Research Building Oxford University, NDM Research Building United Kingdom
Dr Etienne de Villiers Tropical Medicine Oxford University, Kilifi Kenya
Professor Catherine (Sassy) Molyneux Tropical Medicine Oxford University, Kilifi Kenya
Dr Eunice Nduati Tropical Medicine Oxford University, Kilifi Kenya
Dr Amin Hassan Clinical sciences Wellcome Trust Kilify Kenya
Dr Elise M van der Elst Clinical sciences Wellcome Trust Kilify Kenya
Dijkstra M, de Bree GJ, Stolte IG, Davidovich U, Sanders EJ, Prins M, Schim van der Loeff MF. 2017. Development and validation of a risk score to assist screening for acute HIV-1 infection among men who have sex with men. BMC Infect Dis, 17 (1), pp. 425. | Show Abstract | Read more

BACKGROUND: Early treatment of acute HIV-1 infection (AHI) is beneficial for patients and could reduce onward transmission. However, guidelines on whom to test for AHI with HIV-1 RNA testing are lacking. METHODS: A risk score for possible AHI based on literature and expert opinion - including symptoms associated with AHI and early HIV-1 - was evaluated using data from the Amsterdam Cohort Studies among men who have sex with men (MSM). Subsequently, we optimized the risk score by constructing two multivariable logistic regression models: one including only symptoms and one combining symptoms with known risk factors for HIV-1 seroconversion, using generalized estimating equations. Several risk scores were generated from these models and the optimal risk score was validated using data from the Multicenter AIDS Cohort Study. RESULTS: Using data from 1562 MSM with 175 HIV-1 seroconversion visits and 17,271 seronegative visits in the Amsterdam Cohort Studies, the optimal risk score included four symptoms (oral thrush, fever, lymphadenopathy, weight loss) and three risk factors (self-reported gonorrhea, receptive condomless anal intercourse, more than five sexual partners, all in the preceding six months) and yielded an AUC of 0.82. Sensitivity was 76.3% and specificity 76.3%. Validation in the Multicenter AIDS Cohort Study resulted in an AUC of 0.78, sensitivity of 56.2% and specificity of 88.8%. CONCLUSIONS: The optimal risk score had good overall performance in the Amsterdam Cohort Studies and performed comparable (but showed lower sensitivity) in the validation study. Screening for AHI with four symptoms and three risk factors would increase the efficiency of AHI testing and potentially enhance early diagnosis and immediate treatment.

Rutstein SE, Ananworanich J, Fidler S, Johnson C, Sanders EJ, Sued O, Saez-Cirion A, Pilcher CD, Fraser C, Cohen MS et al. 2017. Clinical and public health implications of acute and early HIV detection and treatment: a scoping review. J Int AIDS Soc, 20 (1), pp. 21579. | Show Abstract | Read more

INTRODUCTION: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI. METHODS: We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications. We prioritized research from low- and middle-income countries (LMICs) published in the last fifteen years. RESULTS AND DISCUSSION: Extensive AHI research and limited routine AHI detection and treatment have begun in LMIC. Diagnostic challenges include ease-of-use, suitability for application and distribution in LMIC, and throughput for high-volume testing. Risk score algorithms have been used in LMIC to screen for AHI among individuals with behavioural and clinical characteristics more often associated with AHI. However, algorithms have not been implemented outside research settings. From a clinical perspective, there are substantial immunological and virological benefits to identifying and treating persons with AHI - evading the irreversible damage to host immune systems and seeding of viral reservoirs that occurs during untreated acute infection. The therapeutic benefits require rapid initiation of antiretrovirals, a logistical challenge in the absence of point-of-care testing. From a public health perspective, AHI diagnosis and treatment is critical to: decrease transmission via viral load reduction and behavioural interventions; improve pre-exposure prophylaxis outcomes by avoiding treatment initiation for HIV-seronegative persons with AHI; and, enhance partner services via notification for persons recently exposed or likely transmitting. CONCLUSIONS: There are undeniable clinical and public health benefits to AHI detection and treatment, but also substantial diagnostic and logistical barriers to implementation and scale-up. Effective early ART initiation may be critical for HIV eradication efforts, but widespread use in LMIC requires simple and accurate diagnostic tools. Implementation research is critical to facilitate sustainable integration of AHI detection and treatment into existing health systems and will be essential for prospective evaluation of testing algorithms, point-of-care diagnostics, and efficacious and effective first-line regimens.

Kombo B, Sariola S, Gichuru E, Molyneux S, Sanders EJ, van der Elst E. 2017. "Facing Our Fears": Using facilitated film viewings to engage communities in HIV research involving MSM in Kenya. Cogent Med, 4 (1), pp. 1330728. | Show Abstract | Read more

Kenya is a generally homophobic country where homosexuality is criminalised and people who engage in same sex sexuality face stigma and discrimination. In 2013, we developed a 16 min documentary entitled "Facing Our Fears" that aimed at sharing information on how and why men who have sex with men (MSM) are involved in on-going KEMRI HIV prevention research, and associated community engagement. To consider the film's usefulness as a communication tool, and its perceived security risks in case the film was publicly released, we conducted nine facilitated viewings with 122 individuals representing seven different stakeholder groups. The documentary was seen as a strong visual communication tool with potential to reduce stigma related to homosexuality, and facilitated film viewings were identified as platforms with potential to support open dialogue about HIV research involving MSM. Despite the potential, there were concerns over possible risks to LGBT communities and those working with them following public release. We opted-giving emphasis to the "do no harm" principle-to use the film only in facilitated settings where audience knowledge and attitudes can be carefully considered and discussed. The results highlight the importance of carefully assessing the range of possible impacts when using visuals in community engagement.

Scheibe AP, Duby Z, Brown B, Sanders EJ, Bekker L-G. 2017. Attitude shifts and knowledge gains: Evaluating men who have sex with men sensitisation training for healthcare workers in the Western Cape, South Africa SOUTHERN AFRICAN JOURNAL OF HIV MEDICINE, 18 (1), | Show Abstract | Read more

© 2017. The Authors. Background: Men who have sex with men (MSM) in South Africa experience discrimination from healthcare workers (HCWs), impeding health service access. Objectives: To evaluate the outcomes of an MSM sensitisation training programme for HCWs implemented in the Western Cape province (South Africa). Methods: A training programme was developed to equip HCWs with the knowledge, awareness and skills required to provide non-discriminatory, non-judgemental and appropriate services to MSM. Overall, 592 HCWs were trained between February 2010 and May 2012. Trainees completed self-administered pre- and post-training questionnaires assessing changes in knowledge. Two-sample t-tests for proportion were used to assess changes in specific answers and the Wilcoxon rank-sum test for overall knowledge scores. Qualitative data came from anonymous post-training evaluation forms completed by all trainees, in combination with four focus group discussions (n = 28) conducted six months after their training. Results: Fourteen per cent of trainees had received previous training to counsel clients around penile-anal intercourse, and 16% had previously received training around sexual health issues affecting MSM. There was a statistically significant improvement in overall knowledge scores (80% - 87%, p < 0.0001), specifically around penile-anal intercourse, substance use and depression after the training. Reductions in negative attitudes towards MSM and increased ability for HCWs to provide non-discriminatory care were reported as a result of the training. Conclusion: MSM sensitisation training for HCWs is an effective intervention to increase awareness on issues pertaining to MSM and how to engage around them, reduce discriminatory attitudes and enable the provision of non-judgemental and appropriate services by HCWs.

Masha SC, Wahome E, Vaneechoutte M, Cools P, Crucitti T, Sanders EJ. 2017. High prevalence of curable sexually transmitted infections among pregnant women in a rural county hospital in Kilifi, Kenya. PLoS One, 12 (3), pp. e0175166. | Show Abstract | Read more

BACKGROUND: Women attending antenatal care (ANC) in resource-limited countries are frequently screened for syphilis and HIV, but rarely for other sexually transmitted infections (STIs). We assessed the prevalence of curable STIs, defined as infection with either Chlamydia trachomatis or Neisseria gonorrhoeae or Trichomonas vaginalis, from July to September 2015. METHODS: In a cross-sectional study, women attending ANC at the Kilifi County Hospital, Kenya, had a urine sample tested for C. trachomatis/N. gonorrhoeae by GeneXpert® and a vaginal swab for T. vaginalis by culture. Bacterial vaginosis (BV) was defined as a Nugent score of 7-10 of the Gram stain of a vaginal smear in combination with self-reported vaginal discharge. Genital ulcers were observed during collection of vaginal swabs. All women responded to questions on socio-demographics and sexual health and clinical symptoms of STIs. Predictors for curable STIs were assessed in multivariable logistic regression. RESULTS: A total of 42/202 (20.8%, 95% confidence interval (CI):15.4-27.0) women had a curable STI. The prevalence was 14.9% for C. trachomatis (95% CI:10.2-20.5), 1.0% for N. gonorrhoeae (95% CI: 0.1-3.5), 7.4% for T. vaginalis (95% CI:4.2-12.0), 19.3% for BV (95% CI: 14.1-25.4) and 2.5% for genital ulcers (95% CI: 0.8-5.7). Predictors for infection with curable STIs included women with a genital ulcer (adjusted odds ratio (AOR) = 35.0, 95% CI: 2.7-461.6) compared to women without a genital ulcer, women who used water for cleaning after visiting the toilet compared to those who used toilet paper or other solid means (AOR = 4.1, 95% CI:1.5-11.3), women who reported having sexual debut ≤ 17 years compared to women having sexual debut ≥18 years (AOR = 2.7, 95% CI:1.1-6.6), and BV-positive women (AOR = 2.7, 95% CI:1.1-6.6) compared to BV-negative women. CONCLUSION: One in five women attending ANC had a curable STI. These infections were associated with genital ulcers, hygiene practices, early sexual debut and bacterial vaginosis.

Hassan AS, Pybus OG, Sanders EJ, Albert J, Esbjörnsson J. 2017. Defining HIV-1 transmission clusters based on sequence data. AIDS, 31 (9), pp. 1211-1222. | Show Abstract | Read more

: Understanding HIV-1 transmission dynamics is relevant to both screening and intervention strategies of HIV-1 infection. Commonly, HIV-1 transmission chains are determined based on sequence similarity assessed either directly from a sequence alignment or by inferring a phylogenetic tree. This review is aimed at both nonexperts interested in understanding and interpreting studies of HIV-1 transmission, and experts interested in finding the most appropriate cluster definition for a specific dataset and research question. We start by introducing the concepts and methodologies of how HIV-1 transmission clusters usually have been defined. We then present the results of a systematic review of 105 HIV-1 molecular epidemiology studies summarizing the most common methods and definitions in the literature. Finally, we offer our perspectives on how HIV-1 transmission clusters can be defined and provide some guidance based on examples from real life datasets.

Hassan AS, Hare J, Kamini G, Yindom LM, Kamali A, Karita E, Kilemba W, Price MA, Borrow P, Bjorkman P et al. 2017. A35 Viral evolution and innate immune responses during acute HIV-1 infection and their association with disease pathogenesis. Virus Evol, 3 (Suppl 1), | Read more

Korhonen CJ, Srinivasan S, Huang D, Ko DL, Sanders EJ, Peshu NM, Krieger JN, Muller CH, Coombs RW, Fredricks DN, Graham SM. 2017. Semen Bacterial Concentrations and HIV-1 RNA Shedding Among HIV-1-Seropositive Kenyan Men. J Acquir Immune Defic Syndr, 74 (3), pp. 250-257. | Show Abstract | Read more

INTRODUCTION: HIV-1 is transmitted through semen from men to their sexual partners. Genital infections can increase HIV-1 RNA shedding in semen, but shedding also occurs in the absence of typical pathogens. We hypothesized that higher bacterial concentrations in semen would be associated with higher HIV-1 RNA levels. METHODS: We analyzed semen samples from 42 HIV-1-seropositive Kenyan men using quantitative polymerase chain reaction (PCR) to assess bacterial concentrations and real-time PCR to measure HIV-1 RNA levels. Generalized estimation equations were used to evaluate associations between these 2 measures. Broad-range 16S rRNA gene PCR with pyrosequencing was performed on a subset of 13 samples to assess bacterial community composition. RESULTS: Bacteria were detected in 96.6% of 88 samples by quantitative PCR. Semen bacterial concentration and HIV-1 RNA levels were correlated 0.30 (P = 0.01). The association between bacterial concentration and HIV-1 RNA detection was not significant after adjustment for antiretroviral therapy (ART) (adjusted odds ratio: 1.27, 95% CI: 0.84 to 1.91). Factors associated with semen bacterial concentration included insertive anal sex (adjusted beta 0.92, 95% CI: 0.12 to 1.73) and ART use (adjusted beta: -0.77, 95% CI: -1.50 to 0.04). Among 13 samples with pyrosequencing data, Corynebacterium spp., Staphylococcus spp., and Streptococcus spp. were most frequently detected. CONCLUSION: Most of these HIV-1-infected men had bacteria in their semen. ART use was associated with undetectable semen HIV-1 RNA and lower semen bacterial concentrations, whereas insertive anal sex was associated with higher bacterial concentrations. Additional studies evaluating the relationship between semen bacteria, inflammation, mucosal immunity, and HIV-1 shedding are needed to understand implications for HIV-1 transmission.

Wall KM, Rida W, Haddad LB, Kamali A, Karita E, Lakhi S, Kilembe W, Allen S, Inambao M, Yang AH et al. 2017. Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries. Epidemiology, 28 (2), pp. 224-232. | Show Abstract | Read more

BACKGROUND: Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women. METHODS: From 2006 to 2011, women less than age 40 with incident HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda, South Africa, Uganda, and Zambia. Time-dependent Cox models evaluated associations between pregnancy and HIV disease progression. Clinical progression was defined as a single CD4 measurement <200 cells/μl, percent CD4 <14%, or category C event, with censoring at antiretroviral (ART) initiation for reasons other than prevention of mother-to-child transmission (PMTCT). Immunologic progression was defined as two consecutive CD4s ≤350 cells/μl or a single CD4 ≤350 cells/μl followed by non-PMTCT ART initiation. Generalized estimating equations assessed changes in CD4 before and after pregnancy. RESULTS: Among 222 women, 63 experienced clinical progression during 783.5 person-years at risk (8.0/100). Among 205 women, 87 experienced immunologic progression during 680.1 person-years at risk (12.8/100). The association between pregnancy and clinical progression was adjusted hazard ratio [aHR] = 0.7; 95% confidence interval (CI): 0.2, 1.8. The association between pregnancy and immunologic progression was aHR = 1.7; 95% CI: 0.9, 3.3. Models controlled for age; human leukocyte antigen alleles A*03:01, B*45, B*57; CD4 set point; and HIV-1 subtype. CD4 measurements before versus after pregnancies were not different. CONCLUSIONS: In this cohort, pregnancy was not associated with increased clinical or immunologic HIV progression. Similarly, we did not observe meaningful deleterious associations of pregnancy with CD4s. Our findings suggest that HIV-positive women may become pregnant without harmful health effects occurring during the pregnancy. Evaluation of longer-term impact of pregnancy on progression is warranted.

Micheni M, Kombo BK, Secor A, Simoni JM, Operario D, van der Elst EM, Mugo P, Kanungi J, Sanders EJ, Graham SM. 2017. Health Provider Views on Improving Antiretroviral Therapy Adherence Among Men Who Have Sex with Men in Coastal Kenya. AIDS Patient Care STDS, 31 (3), pp. 113-121. | Show Abstract | Read more

HIV-positive Kenyan men who have sex with men (MSM) are a highly stigmatized group facing barriers to care engagement and antiretroviral therapy (ART) adherence. Because care providers' views are important in improving outcomes, we sought the perspective of those serving MSM patients on how to optimize ART adherence in a setting where same-sex behavior is criminalized. We conducted 4 focus group discussions with a total of 29 healthcare workers (HCWs) experienced in providing HIV care to MSM. The semistructured, open-ended topic guide used was based on an access-information-motivation-proximal cues model of adherence, with added focus on trust in providers, stigma, and discrimination. Detailed facilitator notes and transcripts were translated into English and reviewed for common themes. The HCW identified adherence challenges of MSM patients that are similar to those of the general population, including HIV-related stigma and lack of disclosure. In addition, HCWs noted challenges specific to MSM, such as lack of access to MSM-friendly health services, economic and social challenges due to stigma, difficult relationships with care providers, and discrimination at the clinic and in the community. HCWs recommended clinic staff sensitivity training, use of trained MSM peer navigators, and stigma reduction in the community as interventions that might improve adherence and health outcomes for MSM. Despite noting MSM-specific barriers, HCWs recommended strategies for improving HIV care for MSM in rights-constrained settings that merit future research attention. Most likely, multilevel interventions incorporating both individual and structural factors will be necessary.

Mugo PM, Micheni M, Shangala J, Hussein MH, Graham SM, Rinke de Wit TF, Sanders EJ. 2017. Uptake and Acceptability of Oral HIV Self-Testing among Community Pharmacy Clients in Kenya: A Feasibility Study. PLoS One, 12 (1), pp. e0170868. | Show Abstract | Read more

BACKGROUND: While HIV testing and counselling is a key entry point for treatment as prevention, over half of HIV-infected adults in Kenya are unaware they are infected. Offering HIV self-testing (HST) at community pharmacies may enhance detection of undiagnosed infections. We assessed the feasibility of pharmacy-based HST in Coastal Kenya. METHODS: Staff at five pharmacies, supported by on-site research assistants, recruited adult clients (≥18 years) seeking services indicative of HIV risk. Participants were offered oral HST kits (OraQuick®) at US$1 per test. Within one week of buying a test, participants were contacted for post-test data collection and counselling. The primary outcome was test uptake, defined as the proportion of invited clients who bought tests. Views of participating pharmacy staff were solicited in feedback sessions during and after the study. RESULTS: Between November 2015 and April 2016, 463 clients were invited to participate; 174 (38%) were enrolled; and 161 (35% [95% Confidence Interval (CI) 31-39%]) bought a test. Uptake was higher among clients seeking HIV testing compared to those seeking other services (84% vs. 11%, adjusted risk ratio 6.9 [95% CI 4.9-9.8]). Only 4% of non-testers (11/302) stated inability to pay as the reason they did not take up the test. All but one tester reported the process was easy (29%) or very easy (70%). Demand for HST kits persisted after the study and participating service providers expressed interest in continuing to offer the service. CONCLUSIONS: Pharmacy HST is feasible in Kenya and may be in high demand. The uptake pattern observed suggests that a client-initiated approach is more feasible compared to pharmacy-initiated testing. Price is unlikely to be a barrier if set at about US$1 per test. Further implementation research is required to assess uptake, yield, and linkage to care on a larger scale.

Wahome E, Ngetsa C, Mwambi J, Gelderblom HC, Manyonyi GO, Micheni M, Hassan A, Price MA, Graham SM, Sanders EJ. 2017. Hepatitis B virus incidence and risk factors among human immunodeficiency virus-1 negative men who have sex with men in Kenya Open Forum Infectious Diseases, 4 (1), | Show Abstract | Read more

© The Author 2016. No data exist on hepatitis B virus (HBV) incidence among African men who have sex with men (MSM). We tested plasma samples archived between 2005 and 2014 for HBV core antibody or surface antigen seroconversion in a cohort of 312 initially human immunodeficiency virus (HIV)-1-negative MSM with no evidence of prior HBV infection. Hepatitis B virus incidence was 6.0/100 person- years (95% confidence interval [CI], 3.9-9.1). Hepatitis B virus acquisition was associated with being uncircumcised (adjusted incidence rate ratio [aIRR] , 5.0; 95% CI, 1.5-16.8), recent HIV-1 acquisition (aIRR, 2.9; 95% CI, 1.1-7.7), rape (aIRR, 5.0; 95% CI, 1.2-20.4), and any tertiary education (aIRR, 3.2; 95% CI, 1.1-9.7). African MSM have a substantial risk of HBV acquisition and require vaccination urgently.

Wahome E, Ngetsa C, Mwambi J, Gelderblom HC, Manyonyi GO, Micheni M, Hassan A, Price MA, Graham SM, Sanders EJ. 2017. Hepatitis B Virus Incidence and Risk Factors Among Human Immunodeficiency Virus-1 Negative Men Who Have Sex With Men in Kenya. Open Forum Infect Dis, 4 (1), pp. ofw253. | Show Abstract | Read more

No data exist on hepatitis B virus (HBV) incidence among African men who have sex with men (MSM). We tested plasma samples archived between 2005 and 2014 for HBV core antibody or surface antigen seroconversion in a cohort of 312 initially human immunodeficiency virus (HIV)-1-negative MSM with no evidence of prior HBV infection. Hepatitis B virus incidence was 6.0/100 person-years (95% confidence interval [CI], 3.9-9.1). Hepatitis B virus acquisition was associated with being uncircumcised (adjusted incidence rate ratio [aIRR], 5.0; 95% CI, 1.5-16.8), recent HIV-1 acquisition (aIRR, 2.9; 95% CI, 1.1-7.7), rape (aIRR, 5.0; 95% CI, 1.2-20.4), and any tertiary education (aIRR, 3.2; 95% CI, 1.1-9.7). African MSM have a substantial risk of HBV acquisition and require vaccination urgently.

Ngoi CN, Siqueira J, Li L, Deng X, Mugo P, Graham SM, Price MA, Sanders EJ, Delwart E. 2016. The plasma virome of febrile adult Kenyans shows frequent parvovirus B19 infections and a novel arbovirus (Kadipiro virus). J Gen Virol, 97 (12), pp. 3359-3367. | Show Abstract | Read more

Viral nucleic acids present in the plasma of 498 Kenyan adults with unexplained fever were characterized by metagenomics analysis of 51 sample pools. The highest to lowest fraction of plasma pools was positive for parvovirus B19 (75 %), pegivirus C (GBV-C) (67 %), alpha anellovirus (59 %), gamma anellovirus (55 %), beta anellovirus (41 %), dengue virus genotype 2 (DENV-2) (16 %), human immunodeficiency virus type 1 (6 %), human herpesvirus 6 (6 %), HBV (4 %), rotavirus (4 %), hepatitis B virus (4 %), rhinovirus C (2 %), Merkel cell polyomavirus (MCPyV; 2 %) and Kadipiro virus (2 %). Ranking by overall percentage of viral reads yielded similar results. Characterization of viral nucleic acids in the plasma of a febrile East African population showed a high frequency of parvovirus B19 and DENV infections and detected a reovirus (Kadipiro virus) previously reported only in Asian Culex mosquitoes, providing a baseline to compare with future virome studies to detect emerging viruses in this region.

Prentice HA, Lu H, Price MA, Kamali A, Karita E, Lakhi S, Sanders EJ, Anzala O, Allen S, Goepfert PA et al. 2016. Dynamics and Correlates of CD8 T-Cell Counts in Africans with Primary Human Immunodeficiency Virus Type 1 Infection. J Virol, 90 (22), pp. 10423-10430. | Show Abstract | Read more

In individuals with HIV-1 infection, depletion of CD4+ T cells is often accompanied by a malfunction of CD8+ T cells that are persistently activated and/or exhausted. While the dynamics and correlates of CD4 counts have been well documented, the same does not apply to CD8 counts. Here, we examined the CD8 counts in a cohort of 497 Africans with primary HIV-1 infection evaluated in monthly to quarterly follow-up visits for up to 3 years in the absence of antiretroviral therapy. Statistical models revealed that (i) CD8 counts were relatively steady in the 3- to 36-month period of infection and similar between men and women; (ii) neither geography nor heterogeneity in the HIV-1 set-point viral load could account for the roughly 10-fold range of CD8 counts in the cohort (P > 0.25 in all tests); and (iii) factors independently associated with relatively high CD8 counts included demographics (age ≤ 40 years, adjusted P = 0.010) and several human leukocyte antigen class I (HLA-I) alleles, including HLA-A*03:01 (P = 0.013), B*15:10 (P = 0.007), and B*58:02 (P < 0.001). Multiple sensitivity analyses provided supporting evidence for these novel relationships. Overall, these findings suggest that factors associated with the CD8 count have little overlap with those previously reported for other HIV-1-related outcome measures, including viral load, CD4 count, and CD4/CD8 ratio. IMPORTANCE: Longitudinal data from 497 HIV-1 seroconverters allowed us to systematically evaluate the dynamics and correlates of CD8+ T-cell counts during untreated primary HIV-1 infection in eastern and southern Africans. Our findings suggest that individuals with certain HLA-I alleles, including A*03 (exclusively A*03:01), persistently maintain relatively high CD8 counts following HIV-1 infection, a finding which may offer an intriguing explanation for the recently reported, negative association of A*03 with HIV-1-specific, broadly neutralizing antibody responses. In future studies, attention to HLA-I genotyping data may benefit in-depth understanding of both cellular and humoral immunity, as well as the intrinsic balances of these types of immunity, especially in settings where there is emerging evidence of antagonism between the two arms of adaptive immunity.

Molyneux S, Sariola S, Allman D, Dijkstra M, Gichuru E, Graham S, Kamuya D, Gakii G, Kayemba B, Kombo B et al. 2016. Public/community engagement in health research with men who have sex with men in sub-Saharan Africa: challenges and opportunities. Health Res Policy Syst, 14 (1), pp. 40. | Show Abstract | Read more

BACKGROUND: Community engagement, incorporating elements of the broader concepts of public and stakeholder engagement, is increasingly promoted globally, including for health research conducted in developing countries. In sub-Saharan Africa, community engagement needs and challenges are arguably intensified for studies involving gay, bisexual and other men who have sex with men, where male same-sex sexual interactions are often highly stigmatised and even illegal. This paper contextualises, describes and interprets the discussions and outcomes of an international meeting held at the Kenya Medical Research Institute-Wellcome Trust in Kilifi, Kenya, in November 2013, to critically examine the experiences with community engagement for studies involving men who have sex with men. DISCUSSION: We discuss the ethically charged nature of the language used for men who have sex with men, and of working with 'representatives' of these communities, as well as the complementarity and tensions between a broadly public health approach to community engagement, and a more rights based approach. We highlight the importance of researchers carefully considering which communities to engage with, and the goals, activities, and indicators of success and potential challenges for each. We suggest that, given the unintended harms that can emerge from community engagement (including through labelling, breaches in confidentiality, increased visibility and stigma, and threats to safety), representatives of same-sex populations should be consulted from the earliest possible stage, and that engagement activities should be continuously revised in response to unfolding realities. Engagement should also include less vocal and visible men who have sex with men, and members of other communities with influence on the research, and on research participants and their families and friends. Broader ethics support, advice and research into studies involving men who have sex with men is needed to ensure that ethical challenges - including but not limited to those related to community engagement - are identified and addressed. Underlying challenges and dilemmas linked to stigma and discrimination of men who have sex with men in Africa raise special responsibilities for researchers. Community engagement is an important way of identifying responses to these challenges and responsibilities but itself presents important ethical challenges.

Ngoi CN, Price MA, Fields B, Bonventure J, Ochieng C, Mwashigadi G, Hassan AS, Thiong'o AN, Micheni M, Mugo P et al. 2016. Dengue and Chikungunya Virus Infections among Young Febrile Adults Evaluated for Acute HIV-1 Infection in Coastal Kenya. PLoS One, 11 (12), pp. e0167508. | Show Abstract | Read more

BACKGROUND: Fever is common among patients seeking care in sub-Saharan Africa (sSA), but causes other than malaria are rarely diagnosed. We assessed dengue and chikungunya virus infections among young febrile adults evaluated for acute HIV infection (AHI) and malaria in coastal Kenya. METHODS: We tested plasma samples obtained in a cross-sectional study from febrile adult patients aged 18-35 years evaluated for AHI and malaria at urgent care seeking at seven health facilities in coastal Kenya in 2014-2015. Dengue virus (DENV) and chikungunya virus (CHIKV) were amplified using quantitative real-time reverse-transcription polymerase chain reaction. We conducted logistic regression analyses to determine independent predictors of dengue virus infection. RESULTS: 489 samples that were negative for both AHI and malaria were tested, of which 43 (8.8%, 95% confidence interval [CI]: 6.4-11.7) were positive for DENV infection. No participant was positive for CHIKV infection. DENV infections were associated with clinic visits in the rainy season (adjusted odds ratio (AOR) = 3.0, 95% CI: 1.3-6.5) and evaluation at a private health facility (AOR 5.2, 95% CI: 2.0-13.1) or research health facility (AOR = 25.6, 95% CI: 8.9-73.2) instead of a public health facility. CONCLUSION: A high prevalence of DENV infections was found in febrile young adult patients evaluated for AHI. Our data suggests that DENV, along with AHI and malaria, should be considered in the differential diagnosis of the adult patient seeking care for fever in coastal Kenya.

Cowan FM, Delany-Moretlwe S, Sanders EJ, Mugo NR, Guedou FA, Alary M, Behanzin L, Mugurungi O, Bekker L-G. 2016. PrEP implementation research in Africa: what is new? J Int AIDS Soc, 19 (7(Suppl 6)), pp. 21101. | Show Abstract | Read more

INTRODUCTION: Of the two million new HIV infections in adults in 2014, 70% occurred in sub-Saharan Africa. Several African countries have already approved guidelines for pre-exposure prophylaxis (PrEP) for individuals at substantial risk of HIV as part of combination HIV prevention but key questions remain about how to identify and deliver PrEP to those at greatest need. Throughout the continent, individuals in sero-discordant relationships, and members of key populations (sex workers, men who have sex with men (MSM), transgender women and injection drug users) are likely to benefit from the availability of PrEP. In addition, adolescent girls and young women (AGYW) are at substantial risk in some parts of the continent. It has been estimated that at least three million individuals in Africa are likely to be eligible for PrEP according to WHO's criteria. Tens of demonstration projects are planned or underway across the continent among a range of countries, populations and delivery settings. DISCUSSION: In each of the target populations, there are overarching issues related to (i) creating demand for PrEP, (ii) addressing supply-side issues and (iii) providing appropriate and tailored adherence support. Critical for creating demand for PrEP is the normalization of HIV prevention. Community-level interventions which engage opinion leaders as well as empowerment interventions for those at highest risk will be key. Critical to supply of PrEP is that services are accessible for all, including for stigmatized populations. Establishing accessible integrated services provides the opportunity to address other public health priorities including the unmet need for HIV testing, contraception and sexually transmitted infections treatment. National policies need to include minimum standards for training and quality assurance for PrEP implementation and to address supply chain issues. Adherence support needs to recognize that social and structural factors are likely to have an important influence. Combining interventions that build self-efficacy, empowerment and social cohesion, with evidence-based individualized adherence support for PrEP, are most likely to be effective. CONCLUSIONS: Efficacy of tenfovir-based PrEP is proven but many issues related to implementation remain unclear. Here, we have summarized some of the important implementation questions that need to be assessed as PrEP is rolled out across Africa.

Mugo PM, Wahome EW, Gichuru EN, Mwashigadi GM, Thiong'o AN, Prins HAB, Rinke de Wit TF, Graham SM, Sanders EJ. 2016. Effect of Text Message, Phone Call, and In-Person Appointment Reminders on Uptake of Repeat HIV Testing among Outpatients Screened for Acute HIV Infection in Kenya: A Randomized Controlled Trial. PLoS One, 11 (4), pp. e0153612. | Show Abstract | Read more

BACKGROUND: Following HIV-1 acquisition, many individuals develop an acute retroviral syndrome and a majority seek care. Available antibody testing cannot detect an acute HIV infection, but repeat testing after 2-4 weeks may detect seroconversion. We assessed the effect of appointment reminders on attendance for repeat HIV testing. METHODS: We enrolled, in a randomized controlled trial, 18-29 year old patients evaluated for acute HIV infection at five sites in Coastal Kenya (ClinicalTrials.gov NCT01876199). Participants were allocated 1:1 to either standard appointment (a dated appointment card) or enhanced appointment (a dated appointment card plus SMS and phone call reminders, or in-person reminders for participants without a phone). The primary outcome was visit attendance, i.e., the proportion of participants attending the repeat test visit. Factors associated with attendance were examined by bivariable and multivariable logistic regression. PRINCIPAL FINDINGS: Between April and July 2013, 410 participants were randomized. Attendance was 41% (85/207) for the standard group and 59% (117/199) for the enhanced group, for a relative risk of 1.4 [95% Confidence Interval, CI, 1.2-1.7].Higher attendance was independently associated with older age, study site, and report of transactional sex in past month. Lower attendance was associated with reporting multiple partners in the past two months. CONCLUSIONS: Appointment reminders through SMS, phone calls and in-person reminders increased the uptake of repeat HIV test by forty percent. This low-cost intervention could facilitate detection of acute HIV infections and uptake of recommended repeat testing. TRIAL REGISTRATION: Clinicaltrials.gov NCT01876199.

Landais E, Huang X, Havenar-Daughton C, Murrell B, Price MA, Wickramasinghe L, Ramos A, Bian CB, Simek M, Allen S et al. 2016. Broadly Neutralizing Antibody Responses in a Large Longitudinal Sub-Saharan HIV Primary Infection Cohort. PLoS Pathog, 12 (1), pp. e1005369. | Show Abstract | Read more

Broadly neutralizing antibodies (bnAbs) are thought to be a critical component of a protective HIV vaccine. However, designing vaccines immunogens able to elicit bnAbs has proven unsuccessful to date. Understanding the correlates and immunological mechanisms leading to the development of bnAb responses during natural HIV infection is thus critical to the design of a protective vaccine. The IAVI Protocol C program investigates a large longitudinal cohort of primary HIV-1 infection in Eastern and South Africa. Development of neutralization was evaluated in 439 donors using a 6 cross-clade pseudo-virus panel predictive of neutralization breadth on larger panels. About 15% of individuals developed bnAb responses, essentially between year 2 and year 4 of infection. Statistical analyses revealed no influence of gender, age or geographical origin on the development of neutralization breadth. However, cross-clade neutralization strongly correlated with high viral load as well as with low CD4 T cell counts, subtype-C infection and HLA-A*03(-) genotype. A correlation with high overall plasma IgG levels and anti-Env IgG binding titers was also found. The latter appeared not associated with higher affinity, suggesting a greater diversity of the anti-Env responses in broad neutralizers. Broadly neutralizing activity targeting glycan-dependent epitopes, largely the N332-glycan epitope region, was detected in nearly half of the broad neutralizers while CD4bs and gp41-MPER bnAb responses were only detected in very few individuals. Together the findings suggest that both viral and host factors are critical for the development of bnAbs and that the HIV Env N332-glycan supersite may be a favorable target for vaccine design.

Midoun M, Shangani S, Mbete B, Babu S, Hackman M, van der Elst EM, Sanders EJ, Smith AD, Operario D. 2016. How intersectional constructions of sexuality, culture, and masculinity shape identities and sexual decision-making among men who have sex with men in coastal Kenya. Cult Health Sex, 18 (6), pp. 625-638. | Show Abstract | Read more

Men who have sex with men are increasingly recognised as one of the most vulnerable HIV risk groups in Kenya. Sex between men is highly stigmatised in Kenya, and efforts to provide sexual health services to men who have sex with men require a deeper understanding of their lived experiences; this includes how such men in Kenya construct their sexual identities and how these constructions affect sexual decision-making. Adult self-identified men who have sex with men (n = 26) in Malindi, Kenya, participated in individual interviews to examine sociocultural processes influencing sexual identity construction and decision-making. Four key themes were identified: (1) tensions between perceptions of 'homosexuality' versus being 'African', (2) gender-stereotyped beliefs about sexual positioning, (3) socioeconomic status and limitations to personal agency and (4) objectification and commodification of non-normative sexualities. Findings from this analysis emphasise the need to conceive of same-sex sexuality and HIV risk as context-dependent social phenomena. Multiple sociocultural axes were found to converge and shape sexual identity and sexual decision-making among this population. These axes and their interactive effects should be considered in the design of future interventions and other public health programmes for men who have sex with men in this region.

van der Elst EM, Kombo B, Gichuru E, Omar A, Musyoki H, Graham SM, Smith AD, Sanders EJ, Operario D. 2015. The green shoots of a novel training programme: progress and identified key actions to providing services to MSM at Kenyan health facilities. J Int AIDS Soc, 18 (1), pp. 20226. | Show Abstract | Read more

INTRODUCTION: Although men who have sex with men (MSM) in sub-Saharan Africa are at high risk for HIV acquisition, access to and quality of health and HIV services within this population are negatively affected by stigma and capacity within the health sector. A recently developed online MSM training programme (www.marps-africa.org) was shown to contribute to reductions in MSM prejudice among healthcare providers (HCPs) in coastal Kenya. In this study, we used qualitative methods to explore the provision of MSM healthcare services two years post-training in coastal Kenya. METHODS: From February to July 2014, we held 10 focus group discussions (FGD) with 63 participants, including HCP from 25 facilities, county AIDS coordinators and MSM from local support groups. Participants discussed availability, acceptability and accessibility of HIV healthcare for MSM. HCP also discussed changes in their health service practices after completing the training. FGD were recorded, transcribed verbatim and analyzed using Ritchie and Spencer's "framework approach" for qualitative data. RESULTS: HCPs described continued improvements in their ability to provide service in a non-stigmatizing way to MSM patients since completing the training programme and expressed comfort engaging MSM patients in care. Four additional recommendations for improving MSM healthcare services were identified: 1) expanding the reach of MSM sensitivity training across the medical education continuum; 2) establishing guidelines to manage sexually transmitted anal infections; 3) promoting legal and policy reforms to support integration of MSM-appropriate services into healthcare; and 4) including MSM information in national reporting tools for HIV services. CONCLUSIONS: Positive impacts of this sensitivity and skills training programme were reflected in HCP attitudes two years post-intervention. Scaling-up of efforts will rely on continued policies to include MSM in healthcare programmes to reduce stigma in health settings and guidelines for MSM STI service delivery.

Tang J, Li X, Price MA, Sanders EJ, Anzala O, Karita E, Kamali A, Lakhi S, Allen S, Hunter E et al. 2015. CD4:CD8 lymphocyte ratio as a quantitative measure of immunologic health in HIV-1 infection: findings from an African cohort with prospective data. Front Microbiol, 6 (JUL), pp. 670. | Show Abstract | Read more

In individuals with human immunodeficiency virus type 1 (HIV-1) infection, CD4:CD8 lymphocyte ratio is often recognized as a quantitative outcome that reflects the critical role of both CD4(+) and CD8(+) T-cells in HIV-1 pathogenesis or disease progression. Our work aimed to first establish the dynamics and clinical relevance of CD4:CD8 ratio in a cohort of native Africans and then to examine its association with viral and host factors, including: (i) length of infection, (ii) demographics, (iii) HIV-1 viral load (VL), (iv) change in CD4(+) T-lymphocyte count (CD4 slope), (v) HIV-1 subtype, and (vi) host genetics, especially human leukocyte antigen (HLA) variants. Data from 499 HIV-1 seroconverters with frequent (monthly to quarterly) follow-up revealed that CD4:CD8 ratio was stable in the first 3 years of infection, with a modest correlation with VL and CD4 slope. A relatively normal CD4:CD8 ratio (>1.0) in early infection was associated with a substantial delay in disease progression to severe immunodeficiency (<350 CD4 cells/μl), regardless of other correlates of HIV-1 pathogenesis (adjusted hazards ratio (HR) = 0.43, 95% confidence interval (CI) = 0.29-0.63, P < 0.0001). Low VL (<10,000 copies/ml) and HLA-A*74:01 were the main predictors of CD4:CD8 ratio >1.0, but HLA variants (e.g., HLA-B*57 and HLA-B*81) previously associated with VL and/or CD4 trajectories in eastern and southern Africans had no obvious impact on CD4:CD8 ratio. Collectively, these findings suggest that CD4:CD8 ratio is a robust measure of immunologic health with both clinical and epidemiological implications.

Mugo PM, Sanders EJ, Mutua G, van der Elst E, Anzala O, Barin B, Bangsberg DR, Priddy FH, Haberer JE. 2015. Understanding Adherence to Daily and Intermittent Regimens of Oral HIV Pre-exposure Prophylaxis Among Men Who Have Sex with Men in Kenya AIDS and Behavior, 19 (5), pp. 794-801. | Show Abstract | Read more

© 2014, The Author(s). A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:1:2:1), and followed for 4 months. By electronic monitoring, median adherence for daily dosing was 80 %. Median adherence for intermittent dosing was 71 % per a “relaxed” definition (accounting for off-prescription dosing) and 40 % per a “strict” definition (limited to the prescription). Factors associated with lower adherence included travel, transactional sex, and longer follow-up; higher adherence was associated with daily dosing and an income. The definition of intermittent dosing strongly affects interpretation of adherence. These findings suggest interventions should address challenges of mobility, sex work, and long-term PrEP.

Zhang X, Wallace OL, Domi A, Wright KJ, Driscoll J, Anzala O, Sanders EJ, Kamali A, Karita E, Allen S et al. 2015. Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein. Virology, 482 pp. 218-224. | Show Abstract | Read more

Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies.

Neme S, Wahome E, Mwashigadi G, Thiong'o AN, Stekler JD, Wald A, Sanders EJ, Graham SM. 2015. Prevalence, Incidence, and Clearance of Anogenital Warts in Kenyan Men Reporting High-Risk Sexual Behavior, Including Men Who Have Sex With Men. Open Forum Infect Dis, 2 (2), pp. ofv070. | Show Abstract | Read more

Background.  Human papillomavirus (HPV) causes a spectrum of disease, ranging from warts to cancer. Prevalence, incidence, and factors associated with anogenital warts in East African men are unknown. Methods.  Kenyan men reporting high-risk sexual behavior were inspected for anogenital warts at enrollment and follow-up visits. Logistic regression was performed to identify associations with anogenital warts at baseline. Cox regression was performed to analyze predictors of incident anogenital warts, and Kaplan-Meier curves were used to estimate clearance. Results.  Baseline anogenital wart prevalence in 1137 men was 2.9% (95% confidence interval [CI], 2.0%-4.0%) overall, 2.0% in human immunodeficiency virus (HIV)-uninfected men, and 9.4% in HIV-1-infected men (adjusted odds ratio, 5.43; 95% CI, 2.03-11.29). Over a median of 1.4 years, anogenital wart incidence among 1104 men was 5.3 (95% CI, 4.3-6.5) per 100 person-years. Having HIV-1 infection at baseline (adjusted hazard ratio [aHR], 1.66; 95% CI, 1.01-2.72) or a genital syndrome during follow-up (aHR, 4.78; 95% CI, 3.03-7.56) was associated with increased wart incidence. Wart clearance was lower in HIV-1-infected men (log-rank P<.001). Conclusions.  Anogenital wart prevalence and incidence were increased in HIV-1-infected men, and anogenital warts co-occurred with other genital syndromes. Quadrivalent HPV vaccination should be recommended for young men in settings with high HIV-1 prevalence.

Dijkstra M, van der Elst EM, Micheni M, Gichuru E, Musyoki H, Duby Z, Lange JMA, Graham SM, Sanders EJ. 2015. Emerging themes for sensitivity training modules of African healthcare workers attending to men who have sex with men: a systematic review. Int Health, 7 (3), pp. 151-162. | Show Abstract | Read more

Sensitivity training of front-line African health care workers (HCWs) attending to men who have sex with men (MSM) is actively promoted through national HIV prevention programming in Kenya. Over 970 Kenyan-based HCWs have completed an eight-modular online training free of charge (http://www.marps-africa.org) since its creation in 2011. Before updating these modules, we performed a systematic review of published literature of MSM studies conducted in sub-Saharan Africa (sSA) in the period 2011-2014, to investigate if recent studies provided: important new knowledge currently not addressed in existing online modules; contested information of existing module topics; or added depth to topics covered already. We used learning objectives of the eight existing modules to categorise data from the literature. If data could not be categorised, new modules were suggested. Our review identified 142 MSM studies with data from sSA, including 34 studies requiring module updates, one study contesting current content, and 107 studies reinforcing existing module content. ART adherence and community engagement were identified as new modules. Recent MSM studies conducted in sSA provided new knowledge, contested existing information, and identified new areas of MSM service needs currently unaddressed in the online training.

van der Elst EM, Gichuru E, Muraguri N, Musyoki H, Micheni M, Kombo B, Smith AD, Graham SM, Sanders EJ, Operario D. 2015. Strengthening healthcare providers' skills to improve HIV services for MSM in Kenya. AIDS, 29 Suppl 3 pp. S237-S240. | Show Abstract | Read more

© 2015 Wolters Kluwer Health, Inc. All rights reserved. Research on HIV burden and determinants of HIV risks among MSM in sub-Saharan Africa is now considerable [1]. A meta-analysis of 51 surveys conducted between 2005 and 2013 estimated 18.7% HIV prevalence among MSM, a disproportionately large contribution to the HIV epidemic in sub-Saharan Africa [2,3] . Targeted interventions for MSM could significantly decrease HIV transmission, not only among MSM but also on a population level [4,5]. However, anal intercourse in African societies remains highly stigmatized and HIV public health messaging is still unfocused [6] . Compilation of data on testing behaviour among African MSM derives mostly from studies centred among urban and sex worker MSM [7,8] and indicates that legal policy, social inequality, and inadequate training of healthcare providers (HCPs) discourage MSM from seeking HIV prevention and treatment [9-13] . Addressing HIV and other health needs among MSM in this region cannot be met through the healthcare sector alone. Rigorous structural efforts promoting a skilled healthcare labour force, and community sensitization to protect against unfair treatment will improve the provision of effective and ethical health services for African MSM [11,12,14-21].

Möller LM, Stolte IG, Geskus RB, Okuku HS, Wahome E, Price MA, Prins M, Graham SM, Sanders EJ. 2015. Changes in sexual risk behavior among MSM participating in a research cohort in coastal Kenya. AIDS, 29 Suppl 3 pp. S211-S219. | Show Abstract | Read more

OBJECTIVE: To describe changes in sexual risk behavior among Kenyan MSM who received regular risk reduction counseling (RRC). DESIGN: Data were derived from two cohorts of HIV-1-negative and HIV-1-positive MSM in Kenya. Behavioral data were collected at enrollment and at monthly or quarterly scheduled follow-up visits. At each visit, RRC was provided to all men and HIV-1 testing to seronegative men. METHODS: Random effects logistic and Poisson regression models with time since study entry as main variable of interest were used to evaluate changes in number of sex partners and unprotected sex in the past week, and insertive, receptive, and unprotected anal intercourse in the past 3 months. Analyses were adjusted for HIV-1-status, calendar year of follow-up, and several baseline characteristics. Trends over follow-up time were allowed to differ by HIV-1-status. Men were censored when they seroconverted for HIV. RESULTS: Number of regular and casual sex partners and unprotected anal intercourse decreased in both HIV-1-negative and HIV-1-positive men. Unprotected sex with both regular and casual sex partners decreased more strongly early in follow-up in HIV-1-positive men than in HIV-1-negative men. Decreases in insertive anal intercourse were found for HIV-1-positive men only, whereas decreases in receptive anal intercourse were found for HIV-1-negative men only. CONCLUSION: MSM who were regularly exposed to RRC showed some reductions in sexual risk behavior, but it is uncertain if these reductions are sustained over time. As HIV-1 incidences in Kenyan MSM are very high, RRC should be supported by comprehensive biomedical interventions.

Secor AM, Wahome E, Micheni M, Rao D, Simoni JM, Sanders EJ, Graham SM. 2015. Depression, substance abuse and stigma among men who have sex with men in coastal Kenya. AIDS, 29 Suppl 3 pp. S251-S259. | Show Abstract | Read more

OBJECTIVES: Mental health conditions can erode quality of life and interfere with health-related behaviours such as medication adherence. We aimed to determine the prevalence and correlates of depression and other psychosocial factors among self-identified men who have sex with men (MSM) in coastal Kenya. DESIGN: A cross-sectional survey. METHODS: Psychosocial and mental health characteristics were assessed in an audio computer-assisted self-interview (ACASI) survey among 112 MSM participating in two ongoing HIV-positive and HIV-negative cohorts in Mtwapa, Kenya. RESULTS: One-third of participants met criteria for major depressive disorder [16.1%, 95% confidence interval (95% CI) 9.8-24.2] or other depressive disorder (15.2%, 95% CI 9.1-23.2). Alcohol abuse was reported by 45% of respondents (95% CI 35.2-54.3) and other substance abuse by 59.8% (95% CI 50.1-69.0). Sexual and HIV stigma were moderate, with median scores of 11 [interquartile range (IQR) 6-17, potential range 0-33] and 25 (IQR 23-29, potential range 11-44), respectively. There were significant bivariate correlations between alcohol abuse, other substance abuse, sexual stigma and childhood and recent abuse. In a multivariable linear regression model, sexual stigma (beta = 0.17, 95% CI 0.03-0.32) and marriage to a woman (beta = -2.41 95% CI -4.74 to -0.09) were each associated with depression score. CONCLUSION: We found moderate to high levels of depression and substance abuse, and moderate levels of sexual stigma. These variables were highly inter-correlated and associated with an experience of trauma or abuse. Comprehensive mental health services are needed in this population to address these issues.

Graham SM, Micheni M, Kombo B, Van Der Elst EM, Mugo PM, Kivaya E, Aunon F, Kutner B, Sanders EJ, Simoni JM. 2015. Development and pilot testing of an intervention to promote care engagement and adherence among HIV-positive Kenyan MSM. AIDS, 29 Suppl 3 pp. S241-S249. | Show Abstract | Read more

OBJECTIVES: In many African settings, MSM are a stigmatized group whose access to and engagement in HIV care may be challenging. Our aim was to design a targeted, culturally appropriate intervention to promote care engagement and antiretroviral therapy (ART) adherence for MSM in coastal Kenya, and describe intervention safety, feasibility, and acceptability based upon a small pilot study. DESIGN: Based on qualitative work including in-depth interviews with HIV-positive MSM and focus groups with providers, we developed a tailored intervention and conducted a pilot test to refine intervention materials and procedures. METHODS: The Shikamana intervention combines modified Next-Step Counseling by trained providers, support from a trained peer navigator, and tailored use of SMS messaging, phone calls, and discrete pill carriers. Providers, including counselors and clinicians, work together with peer navigators as a case management team. RESULTS: Forty HIV-positive MSM aged 19-51 participated in intervention development and testing. Six counselors, three clinical officers, and four MSM peers were trained in intervention procedures. Of 10 ART-naïve participants who enrolled in the pilot, eight completed follow-up with no adverse events reported. One participant was lost to follow-up after 2 months and another failed to initiate ART despite ongoing counseling. No adverse events were reported. Staff feedback and exit interviews rated the intervention as feasible and acceptable. CONCLUSION: This adherence support intervention tailored for Kenyan MSM was well tolerated, feasible, and acceptable in the pilot phase. A randomized controlled trial of a scaled-up programme to estimate intervention efficacy is ongoing.

Smith AD, Muhaari AD, Agwanda C, Kowuor D, van der Elst E, Davies A, Graham SM, Jaffe HW, Sanders EJ. 2015. Heterosexual behaviours among men who sell sex to men in coastal Kenya. AIDS, 29 Suppl 3 pp. S201-S210. | Show Abstract | Read more

OBJECTIVE: African men who have sex with men often sell sex to men, and MSM who sell sex (MSM-SW) often also have female partners. We compared sexual risk behaviour of MSM-SW who were sexually active with female partners (bisexual MSW) to MSM-SW with only male partners (exclusive MSW). DESIGN: Descriptive behavioural study METHODS: : A novel, validated daily event and partner diary self-completed by 82 MSM who sold sex over a follow-up period of 42 days with weekly review. Cumulative individual counts of sex and condomless sex were compiled by partner characteristics. The incidence of specific partnerships and sex acts were compared within and between bisexual and exclusive MSW. RESULTS: Most (59%) MSM-SW reported female partners during follow-up. The majority of both male and female partners were cash-paying clients originating locally. Bisexual MSW reported a similar rate of condomless sex with male and female partners, but significantly fewer male partners than exclusive MSW. Bisexual MSW had lower HIV prevalence, were more likely to only report insertive anal sex roles, and reported lower frequencies of condomless receptive anal sex than exclusive MSW. CONCLUSION: Bisexually active male sex workers in coastal Kenya create HIV and other sexually transmitted infection transmission pathways to partners and clients in both MSM and heterosexual networks, but differed from exclusive MSW in having lower HIV acquisition and transmission risks. Epidemiological projection methods are liable to overestimate bridging potential of MSM-SW and MSM populations without account for systematic differences in risk within these populations.

Sanders EJ, Jaffe H, Musyoki H, Muraguri N, Graham SM. 2015. Kenyan MSM: no longer a hidden population. AIDS, 29 Suppl 3 pp. S195-S199. | Read more

Micheni M, Rogers S, Wahome E, Darwinkel M, van der Elst E, Gichuru E, Graham SM, Sanders EJ, Smith AD. 2015. Risk of sexual, physical and verbal assaults on men who have sex with men and female sex workers in coastal Kenya. AIDS, 29 Suppl 3 pp. S231-S236. | Show Abstract | Read more

BACKGROUND: Violence toward MSM and female sex workers (FSW) is associated with HIV risk, and its prevention is prioritized in international HIV/AIDS policy. METHODS: Sociodemographic and behavioural data derived from HIV risk and follow-up cohorts including MSM and FSW in coastal Kenya between 2005 and 2014 was used to estimate the risk of rape, physical assault and verbal abuse, and to assess associations between first occurrence of assault with individual and recent behavioural factors. RESULTS: Incidence of first reported rape was similar for MSM [3.9, confidence interval (CI) 3.1-5.0 per 100 person-years (pyrs)] and FSW (4.8 CI 3.5-6.4 per 100 pyrs), P = 0.22. Incidence of first reported physical and verbal assault was higher for FSW than MSM (21.1 versus 12.9 per 100 pyrs, P = 0.14 and 51.3 versus 30.9 per 100 pyrs, P = 0.03 respectively). Recent alcohol use was associated with reporting of all forms of assault by MSM [adjusted odds ratio (AOR) 1.8, CI 0.9-3.5] and FSW (AOR 4.4, CI 1.41-14.0), as was recent sale of sex for MSM (AOR 2.0, CI 1.1-3.8). Exclusive sex with men, active sex work, and group sex were also specifically associated with reporting rape for MSM. Perpetrators of sexual and verbal assault were usually unknown, whilst perpetrators of physical violence toward FSW were usually regular sexual partners. CONCLUSION: MSM and FSW experienced a similarly high incidence of sexual assault in coastal Kenya, in addition to physical and verbal assault. Current national policies focus heavily on gender-based violence against women and young girls, but need to be inclusive of MSM and FSW.

Sanders EJ, Wahome E, Powers KA, Werner L, Fegan G, Lavreys L, Mapanje C, McClelland RS, Garrett N, Miller WC, Graham SM. 2015. Targeted screening of at-risk adults for acute HIV-1 infection in sub-Saharan Africa. AIDS, 29 Suppl 3 pp. S221-S230. | Show Abstract | Read more

BACKGROUND: Patients with acute HIV-1 infection (AHI) have elevated infectivity, but cannot be diagnosed using antibody-based testing. Approaches to screen patients for AHI are urgently needed to enable counselling and treatment to reduce onward transmission. METHODS: We pooled data from four African studies of high-risk adults that evaluated symptoms and signs compatible with acute retroviral syndrome and tested for HIV-1 at each visit. AHI was defined as detectable plasma viral load or p24 antigen in an HIV-1-antibody-negative patient who subsequently seroconverted. Using generalized estimating equation, we identified symptoms, signs, and demographic factors predictive of AHI, adjusting for study site. We assigned a predictor score to each statistically significant predictor based on its beta coefficient, summing predictor scores to calculate a risk score for each participant. We evaluated the performance of this algorithm overall and at each site. RESULTS: We compared 122 AHI visits with 45 961 visits by uninfected patients. Younger age (18-29 years), fever, fatigue, body pains, diarrhoea, sore throat, and genital ulcer disease were independent predictors of AHI. The overall area under the receiver operating characteristics curve (AUC) for the algorithm was 0.78, with site-specific AUCs ranging from 0.61 to 0.89. A risk score of at least 2 would indicate AHI testing for 5-50% of participants, substantially decreasing the number needing testing. CONCLUSION: Our targeted risk score algorithm based on seven characteristics reduced the number of patients needing AHI testing and had good performance overall. We recommend this risk score algorithm for use by HIV programs in sub-Saharan Africa with capacity to test high-risk patients for AHI.

Hassan AS, Mwaringa SM, Ndirangu KK, Sanders EJ, de Wit TFR, Berkley JA. 2015. Incidence and predictors of attrition from antiretroviral care among adults in a rural HIV clinic in Coastal Kenya: a retrospective cohort study. BMC Public Health, 15 (1), pp. 478. | Show Abstract | Read more

BACKGROUND: Scale up of antiretroviral therapy (ART) has led to substantial declines in HIV related morbidity and mortality. However, attrition from ART care remains a major public health concern and has been identified as one of the key reportable indicators in assessing the success of ART programs. This study describes the incidence and predictors of attrition among adults initiating ART in a rural HIV clinic in Coastal Kenya. METHODS: A retrospective cohort study design was used. Adults (≥ 15 years) initiated ART between January 2008 and December 2010 were followed up for two years. Attrition was defined as individuals who were either reported dead or lost to follow up (LFU, ≥ 180 days late since the last clinic visit). Kaplan Meier survival probabilities and Weibull baseline hazard regression analyses were used to model the incidence and predictors of time to attrition. RESULTS: Of the 928 eligible participants, 308 (33.2% [95% CI, 30.2 - 36.3]) underwent attrition at an incident rate of 23.1 (95% CI, 20.6 - 25.8)/100 pyo. Attrition at 6 and 12 months was 18.4% (95% CI, 16.0 - 21.1) and 23.2% (95% CI, 19.9 - 25.3) respectively. Gender (male vs. female, adjusted hazard ratio [95% CI], p-value: 1.5 [1.1 - 2.0], p = 0.014), age (15 - 24 vs. ≥ 45 years, 2.2 [1.3 - 3.7], p = 0.034) and baseline CD4 T-cell count (100 - 350 cells/uL vs. < 100 cells/uL, 0.5 [0.3 - 0.7], p = 0.002) were independent predictors of time to attrition. CONCLUSIONS: A third of individuals initiating ART were either reported dead or LFU during two years of care, with more than a half of these occurring within six months of treatment initiation. Practical and sustainable biomedical interventions and psychosocial support systems are warranted to improve ART retention in this setting.

Kamali A, Price MA, Lakhi S, Karita E, Inambao M, Sanders EJ, Anzala O, Latka MH, Bekker L-G, Kaleebu P et al. 2015. Creating an African HIV clinical research and prevention trials network: HIV prevalence, incidence and transmission. PLoS One, 10 (1), pp. e0116100. | Show Abstract | Read more

HIV epidemiology informs prevention trial design and program planning. Nine clinical research centers (CRC) in sub-Saharan Africa conducted HIV observational epidemiology studies in populations at risk for HIV infection as part of an HIV prevention and vaccine trial network. Annual HIV incidence ranged from below 2% to above 10% and varied by CRC and risk group, with rates above 5% observed in Zambian men in an HIV-discordant relationship, Ugandan men from Lake Victoria fishing communities, men who have sex with men, and several cohorts of women. HIV incidence tended to fall after the first three months in the study and over calendar time. Among suspected transmission pairs, 28% of HIV infections were not from the reported partner. Volunteers with high incidence were successfully identified and enrolled into large scale cohort studies. Over a quarter of new cases in couples acquired infection from persons other than the suspected transmitting partner.

Mugo PM, Prins HAB, Wahome EW, Mwashigadi GM, Thiong'o AN, Gichuru E, Omar A, Graham SM, Sanders EJ. 2015. Engaging young adult clients of community pharmacies for HIV screening in Coastal Kenya: a cross-sectional study. Sex Transm Infect, 91 (4), pp. 257-259. | Show Abstract | Read more

BACKGROUND: Adults in developing countries frequently use community pharmacies as the first and often only source of care. The objective of this study was to assess the success of pharmacy referrals and uptake of HIV testing by young adult clients of community pharmacies in the context of a screening programme for acute HIV-1 infection (AHI). METHODS: We requested five pharmacies to refer clients meeting predefined criteria (ie, 18-29 years of age and requesting treatment for fever, diarrhoea, sexually transmitted infection (STI) symptoms or body pains) for HIV-1 testing and AHI screening at selected clinics. Using multivariable logistical regression, we determined client characteristics associated with HIV-1 test uptake. RESULTS: From February through July 2013, 1490 pharmacy clients met targeting criteria (range of weekly averages across pharmacies: 4-35). Of these, 1074 (72%) accepted a referral coupon, 377 (25%) reported at a study clinic, 353 (24%) were HIV-1 tested and 127 (9%) met criteria for the AHI study. Of those tested, 14 (4.0%) were HIV-1 infected. Test uptake varied significantly by referring pharmacy and was higher for clients who presented at the pharmacy without a prescription versus those with a prescription, and for clients who sought care for STI symptoms. CONCLUSIONS: About a quarter of targeted pharmacy clients took up HIV-1 testing. Clients seeking care directly at the pharmacy (ie, without a prescription) and those with STI symptoms were more likely to take up HIV-1 testing. Engagement of adult pharmacy clients for HIV-1 screening may identify undiagnosed individuals and offers opportunities for HIV-1 prevention research.

Mugo PM, Sanders EJ, Mutua G, van der Elst E, Anzala O, Barin B, Bangsberg DR, Priddy FH, Haberer JE. 2015. Understanding Adherence to Daily and Intermittent Regimens of Oral HIV Pre-exposure Prophylaxis Among Men Who Have Sex with Men in Kenya. AIDS Behav, 19 (5), pp. 794-801. | Show Abstract | Read more

A qualitative assessment of Kenyan men who have sex with men taking daily and intermittent oral HIV pre-exposure prophylaxis (PrEP) found stigma, sex work, mobility, and alcohol impacted adherence. We analyzed quantitative data from the same cohort to explore different definitions of intermittent adherence. Volunteers were randomized to daily emtricitabine/tenofovir or placebo, or intermittent (prescription: Mondays/Fridays/after sex, maximum 1 dose/day) emtricitabine/tenofovir or placebo (2:1:2:1), and followed for 4 months. By electronic monitoring, median adherence for daily dosing was 80 %. Median adherence for intermittent dosing was 71 % per a "relaxed" definition (accounting for off-prescription dosing) and 40 % per a "strict" definition (limited to the prescription). Factors associated with lower adherence included travel, transactional sex, and longer follow-up; higher adherence was associated with daily dosing and an income. The definition of intermittent dosing strongly affects interpretation of adherence. These findings suggest interventions should address challenges of mobility, sex work, and long-term PrEP.

Baxi SM, Liu A, Bacchetti P, Mutua G, Sanders EJ, Kibengo FM, Haberer JE, Rooney J, Hendrix CW, Anderson PL et al. 2015. Comparing the novel method of assessing PrEP adherence/exposure using hair samples to other pharmacologic and traditional measures. J Acquir Immune Defic Syndr, 68 (1), pp. 13-20. | Show Abstract | Read more

OBJECTIVE: The efficacy of pre-exposure prophylaxis (PrEP) in HIV will diminish with poor adherence; pharmacologic measures of drug exposure have proven critical to PrEP trial interpretation. We assessed drug exposure in hair against other pharmacologic and more routinely used measures to assess pill-taking. DESIGN: Participants were randomized to placebo, daily PrEP, or intermittent PrEP to evaluate safety and tolerability of daily versus intermittent tenofovir/emtricitabine (TFV/FTC) in 2 phase II PrEP clinical trials conducted in Africa. Different measures of drug exposure, including self-report, medication event monitoring system (MEMS)-caps openings, and TFV/FTC levels in hair and other biomatrices were compared. METHODS: At weeks 8 and 16, self-reported pill-taking, MEMS-caps openings, and TFV/FTC levels in hair, plasma, and peripheral blood mononuclear cells (PBMCs) were measured. Regression models evaluated predictors of TFV/FTC concentrations in the 3 biomatrices; correlation coefficients between pharmacologic and nonpharmacologic measures were calculated. Both trials were registered on ClinicalTrials.gov (NCT00931346/NCT00971230). RESULTS: Hair collection was highly feasible and acceptable (100% in week 8; 96% in week 16). In multivariate analysis, strong associations were seen between pharmacologic measures and MEMS-caps openings (all P < 0.001); self-report was only weakly associated with pharmacologic measures. TFV/FTC hair concentrations were significantly correlated with levels in plasma and PBMCs (correlation coefficients, 0.41-0.86, all P < 0.001). CONCLUSIONS: Measuring TFV/FTC exposure in small hair samples in African PrEP trials was feasible and acceptable. Hair levels correlated strongly with PBMC, plasma concentrations, and MEMS-caps openings. As in other PrEP trials, self-report was the weakest measure of exposure. Further study of hair TFV/FTC levels in PrEP trials and demonstration projects to assess adherence/exposure is warranted.

Gichuru E, Sariola S, Van der Elst EM, Mugo P, Micheni M, Graham SM, Molyneux C, Sanders EJ. 2014. 'Facing our Fears': Facilitated Film Viewings as a Community Engagement Tool in Research Involving MSM in Kenya. AIDS Res Hum Retroviruses, 30 Suppl 1 (S1), pp. A132-A133. | Read more

Gilmour J, Kamali A, Karita E, Kilembe W, Sanders EJ, Anzala O, Allen S, Edward V, Priddy F, Price MA et al. 2014. African Early Infection Cohort as a Platform for Vaccine Discovery: The IAVI Protocol C Experience. AIDS Res Hum Retroviruses, 30 Suppl 1 (S1), pp. A31. | Read more

Li X, Price MA, He D, Kamali A, Karita E, Lakhi S, Sanders EJ, Anzala O, Amornkul PN, Allen S et al. 2014. Host genetics and viral load in primary HIV-1 infection: clear evidence for gene by sex interactions. Hum Genet, 133 (9), pp. 1187-1197. | Show Abstract | Read more

Research in the past two decades has generated unequivocal evidence that host genetic variations substantially account for the heterogeneous outcomes following human immunodeficiency virus type 1 (HIV-1) infection. In particular, genes encoding human leukocyte antigens (HLA) have various alleles, haplotypes, or specific motifs that can dictate the set-point (a relatively steady state) of plasma viral load (VL), although rapid viral evolution driven by innate and acquired immune responses can obscure the long-term relationships between HLA genotypes and HIV-1-related outcomes. In our analyses of VL data from 521 recent HIV-1 seroconverters enrolled from eastern and southern Africa, HLA-A*03:01 was strongly and persistently associated with low VL in women (frequency = 11.3 %, P < 0.0001) but not in men (frequency = 7.7 %, P = 0.66). This novel sex by HLA interaction (P = 0.003, q = 0.090) did not extend to other frequent HLA class I alleles (n = 34), although HLA-C*18:01 also showed a weak association with low VL in women only (frequency = 9.3 %, P = 0.042, q > 0.50). In a reduced multivariable model, age, sex, geography (clinical sites), previously identified HLA factors (HLA-B*18, B*45, B*53, and B*57), and the interaction term for female sex and HLA-A*03:01 collectively explained 17.0 % of the overall variance in geometric mean VL over a 3-year follow-up period (P < 0.0001). Multiple sensitivity analyses of longitudinal and cross-sectional VL data yielded consistent results. These findings can serve as a proof of principle that the gap of "missing heritability" in quantitative genetics can be partially bridged by a systematic evaluation of sex-specific associations.

Sanders EJ. 2014. HIV-1 testing of young febrile adults seeking care for fever in sub-Sahara Africa. Int Health, 6 (2), pp. 77-78. | Read more

Prins HAB, Mugo P, Wahome E, Mwashigadi G, Thiong'o A, Smith A, Sanders EJ, Graham SM. 2014. Diagnosing acute and prevalent HIV-1 infection in young African adults seeking care for fever: a systematic review and audit of current practice. Int Health, 6 (2), pp. 82-92. | Show Abstract | Read more

Fever is a common complaint in HIV-1 infected adults and may be a presenting sign of acute HIV-1 infection (AHI). We investigated the extent to which HIV-1 infection was considered in the diagnostic evaluation of febrile adults in sub-Saharan Africa (SSA) through a systematic review of published literature and guidelines in the period 2003-2014. We also performed a detailed audit of current practice for the evaluation of febrile young adults in coastal Kenya. Our review identified 43 studies investigating the aetiology of fever in adult outpatients in SSA. While the guidelines identified recommend testing for HIV-1 infection, none mentioned AHI. In our audit of current practice at nine health facilities, only 189 out of 1173 (16.1%) patients, aged 18-29 years, were tested for HIV-1. In a detailed record review, only 2 out of 39 (5.1%) young adults seeking care for fever were tested for HIV-1, and the possibility of AHI was not mentioned. Available literature on adult outpatients presenting with fever is heavily focused on diagnosing malaria and guidelines are poorly defined in terms of evaluating aetiologies other than malaria. Current practice in coastal Kenya shows poor uptake of provider-initiated HIV-1 testing and AHI is not currently considered in the differential diagnosis.

Sanders EJ, Wahome E, Okuku HS, Thiong'o AN, Smith AD, Duncan S, Mwambi J, Shafi J, McClelland RS, Graham SM. 2014. Evaluation of WHO screening algorithm for the presumptive treatment of asymptomatic rectal gonorrhoea and chlamydia infections in at-risk MSM in Kenya. Sex Transm Infect, 90 (2), pp. 94-99. | Show Abstract | Read more

OBJECTIVES: The WHO recommends that men who have sex with men (MSM) reporting unprotected receptive anal intercourse (RAI) and either multiple partners or a partner with a sexually transmitted infection (STI) in the past 6 months should be presumptively treated for asymptomatic rectal Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) infections. We evaluated this recommendation in a cohort of 'high-risk' MSM in Coastal Kenya. METHODS: We assessed presence of genitourinary and rectal symptoms, and determined prevalence and 3-month incidence of rectal NG and CT infections. We performed nucleic acid amplification testing of urine and rectal swab samples collected from MSM followed prospectively, and assessed predictive values of the WHO algorithm at baseline screening. RESULTS: Of 244 MSM screened, 240 (98.4%) were asymptomatic, and 147 (61.3%) reported any RAI in the past 6 months. Among 85 (35.4%) asymptomatic MSM meeting criteria for the WHO presumptive treatment (PT) recommendation, we identified 20 with rectal infections (six NG, 12 CT and two NG-CT co-infections). Among 62 asymptomatic MSM who did not meet criteria, we identified seven who were infected. The sensitivity and specificity of the WHO algorithm were 74.1% (95% CI 53.7% to 88.9%) and 45.8% (95% CI 36.7% to 55.2%), respectively. The 3-month incidence of any rectal NG or CT infection in asymptomatic men reporting any RAI was 39.7 (95% CI 24.3 to 64.8) per 100 person-years. CONCLUSIONS: About one-third of asymptomatic MSM were eligible to receive PT for NG and CT infections. Among MSM who would qualify for PT of rectal STIs, the number needed to treat in order to treat one infection was four. Our results support the value of the WHO screening algorithm and recommended PT strategy in this population.

Sanders EJ, Mugo P, Prins HAB, Wahome E, Thiong'o AN, Mwashigadi G, van der Elst EM, Omar A, Smith AD, Graham SM. 2014. Acute HIV-1 infection is as common as malaria in young febrile adults seeking care in coastal Kenya. AIDS, 28 (9), pp. 1357-1363. | Show Abstract | Read more

BACKGROUND: Febrile adults are usually not tested for acute HIV-1 infection (AHI) in Africa. We assessed a strategy to diagnose AHI among young adult patients seeking care. METHODS: Young adults (<30 years) who met predefined AHI criteria at care seeking, including fever, sexually transmitted disease symptoms, diarrhoea, body pains or multiple partners were referred from five pharmacies and screened at five health facilities. Prevalent HIV-1 was diagnosed by nationally recommended serial rapid HIV-1 testing. Willing HIV-1-negative patients were evaluated for AHI, defined as a positive p24 antigen test, and subsequent seroconversion or RNA detection. Febrile patients evaluated for AHI were also screened for malaria using a rapid test, with PCR confirmation of positives. RESULTS: In 3602 adults seeking care, overall HIV-1 prevalence was 3.9%: 7.6% (68/897) among patients meeting AHI criteria vs. 2.6% (71/2705) among those who did not (P < 0.001). AHI was diagnosed in five of 506 HIV-1-negative or discordant patients who met AHI risk criteria and were completely evaluated [prevalence 1.0%, 95% confidence interval (CI) 0.3-2.3%]. Of these five AHI cases, four were diagnosed among the 241 patients with fever (prevalence 1.7%, 95% CI 0.5-4.2%), vs. one among 265 non-febrile patients (prevalence 0.4%, 95% CI 0.0-2.0%, P = 0.1). Malaria was confirmed by PCR in four (1.7%) of the 241 febrile patients. CONCLUSION: AHI was as common as confirmed malaria in young febrile adults seeking care. An AHI detection strategy targeting young febrile adults seeking care at pharmacies and health facilities is feasible and should be considered as an HIV-prevention strategy in high-transmission settings.

Prentice HA, Price MA, Porter TR, Cormier E, Mugavero MJ, Kamali A, Karita E, Lakhi S, Sanders EJ, Anzala O et al. 2014. Dynamics of viremia in primary HIV-1 infection in Africans: insights from analyses of host and viral correlates. Virology, 449 pp. 254-262. | Show Abstract | Read more

In HIV-1 infection, plasma viral load (VL) has dual implications for pathogenesis and public health. Based on well-known patterns of HIV-1 evolution and immune escape, we hypothesized that VL is an evolving quantitative trait that depends heavily on duration of infection (DOI), demographic features, human leukocyte antigen (HLA) genotypes and viral characteristics. Prospective data from 421 African seroconverters with at least four eligible visits did show relatively steady VL beyond 3 months of untreated infection, but host and viral factors independently associated with cross-sectional and longitudinal VL often varied by analytical approaches and sliding time windows. Specifically, the effects of age, HLA-B(⁎)53 and infecting HIV-1 subtypes (A1, C and others) on VL were either sporadic or highly sensitive to time windows. These observations were strengthened by the addition of 111 seroconverters with 2-3 eligible VL results, suggesting that DOI should be a critical parameter in epidemiological and clinical studies.

Li X, Price MA, He D, Kamali A, Karita E, Lakhi S, Sanders EJ, Anzala O, Amornkul PN, Allen S et al. 2014. Host genetics and viral load in primary HIV-1 infection: clear evidence for gene by sex interactions Human Genetics, 133 (9), pp. 1187-1197. | Show Abstract | Read more

© 2014, The Author(s). Research in the past two decades has generated unequivocal evidence that host genetic variations substantially account for the heterogeneous outcomes following human immunodeficiency virus type 1 (HIV-1) infection. In particular, genes encoding human leukocyte antigens (HLA) have various alleles, haplotypes, or specific motifs that can dictate the set-point (a relatively steady state) of plasma viral load (VL), although rapid viral evolution driven by innate and acquired immune responses can obscure the long-term relationships between HLA genotypes and HIV-1-related outcomes. In our analyses of VL data from 521 recent HIV-1 seroconverters enrolled from eastern and southern Africa, HLA-A*03:01 was strongly and persistently associated with low VL in women (frequency = 11.3 %, P  <  0.0001) but not in men (frequency = 7.7 %, P = 0.66). This novel sex by HLA interaction (P = 0.003, q = 0.090) did not extend to other frequent HLA class I alleles (n = 34), although HLA-C*18:01 also showed a weak association with low VL in women only (frequency = 9.3 %, P = 0.042, q  >  0.50). In a reduced multivariable model, age, sex, geography (clinical sites), previously identified HLA factors (HLA-B*18, B*45, B*53, and B*57), and the interaction term for female sex and HLA-A*03:01 collectively explained 17.0 % of the overall variance in geometric mean VL over a 3-year follow-up period (P  <  0.0001). Multiple sensitivity analyses of longitudinal and cross-sectional VL data yielded consistent results. These findings can serve as a proof of principle that the gap of “missing heritability” in quantitative genetics can be partially bridged by a systematic evaluation of sex-specific associations.

Hassan AS, Nabwera HM, Mwaringa SM, Obonyo CA, Sanders EJ, Rinke de Wit TF, Cane PA, Berkley JA. 2014. HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study. AIDS Res Ther, 11 (1), pp. 9. | Show Abstract | Read more

BACKGROUND: An increasing number of people on antiretroviral therapy (ART) in sub-Saharan Africa has led to declines in HIV related morbidity and mortality. However, virologic failure (VF) and acquired drug resistance (ADR) may negatively affect these gains. This study describes the prevalence and correlates of HIV-1 VF and ADR among first-line ART experienced adults at a rural HIV clinic in Coastal Kenya. METHODS: HIV-infected adults on first-line ART for ≥6 months were cross-sectionally recruited between November 2008 and March 2011. The primary outcome was VF, defined as a one-off plasma viral load of ≥400 copies/ml. The secondary outcome was ADR, defined as the presence of resistance associated mutations. Logistic regression and Fishers exact test were used to describe correlates of VF and ADR respectively. RESULTS: Of the 232 eligible participants on ART over a median duration of 13.9 months, 57 (24.6% [95% CI: 19.2 - 30.6]) had VF. Fifty-five viraemic samples were successfully amplified and sequenced. Of these, 29 (52.7% [95% CI: 38.8 - 66.3]) had at least one ADR, with 25 samples having dual-class resistance mutations. The most prevalent ADR mutations were the M184V (n = 24), K103N/S (n = 14) and Y181C/Y/I/V (n = 8). Twenty-six of the 55 successfully amplified viraemic samples (47.3%) did not have any detectable resistance mutation. Younger age (15-34 vs. ≥35 years: adjusted odd ratios [95% CI], p-value: 0.3 [0.1-0.6], p = 0.002) and unsatisfactory adherence (<95% vs. ≥95%: 3.0 [1.5-6.5], p = 0.003) were strong correlates of VF. Younger age, unsatisfactory adherence and high viral load were also strong correlates of ADR. CONCLUSIONS: High levels of VF and ADR were observed in younger patients and those with unsatisfactory adherence. Youth-friendly ART initiatives and strengthened adherence support should be prioritized in this Coastal Kenyan setting. To prevent unnecessary/premature switches, targeted HIV drug resistance testing for patients with confirmed VF should be considered.

van der Elst EM, Gichuru E, Omar A, Kanungi J, Duby Z, Midoun M, Shangani S, Graham SM, Smith AD, Sanders EJ, Operario D. 2013. Experiences of Kenyan healthcare workers providing services to men who have sex with men: qualitative findings from a sensitivity training programme Journal of the International AIDS Society, 16 (4(Suppl 3)), | Read more

Amornkul PN, Karita E, Kamali A, Rida WN, Sanders EJ, Lakhi S, Price MA, Kilembe W, Cormier E, Anzala O et al. 2013. Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub-Saharan Africa. AIDS, 27 (17), pp. 2775-2786. | Show Abstract | Read more

OBJECTIVE: To describe immunologic, virologic, and clinical HIV disease progression by HIV-1 subtype among Africans with well documented estimated dates of HIV infection (EDIs). DESIGN: Prospective cohort. METHODS: Adults and youth with documented HIV-1 infection in the past 12 months were recruited from seroincidence cohorts in East and Southern Africa and followed at 3-6 month intervals. Blood for lymphocyte subset and viral load determination was collected at each visit. Pol was sequenced from the first positive specimen to ascertain subtype. Preantiretroviral therapy disease progression was measured by three time-to-event endpoints: CD4 cell count 350 cells/μl or less, viral load measurement at least 1 × 10 copies/ml, and clinical AIDS. RESULTS: From 2006 to 2011, 615 participants were enrolled at nine research centers in Kenya, Rwanda, South Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed. Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%). After adjustment for age, sex, and human leukocyte antigen alleles in Cox regression analyses, subtype C-infected participants progressed faster than subtype A to all three endpoints [CD4 hazard ratio 1.60, 95% (confidence interval) CI 1.16, 2.20; viral load hazard ratio 1.59, 95% CI 1.12, 2.25; and AIDS hazard ratio 1.60, 95% CI 1.11, 2.31). Subtype D-infected participants reached high viral load more rapidly (hazard ratio 1.61, 95% CI 1.01, 2.57) and progressed nearly twice as fast to AIDS compared to subtype A (hazard ratio 1.93, 95% CI 1.21, 3.09). CONCLUSION: Subtype-specific differences in HIV disease progression suggest that the local subtype distribution be considered when planning HIV programs and designing and defining clinical endpoints for HIV prevention trials.

Bezemer D, Faria NR, Hassan A, Hamers RL, Mutua G, Anzala O, Mandaliya K, Cane P, Berkley JA, Rinke de Wit TF et al. 2014. HIV Type 1 transmission networks among men having sex with men and heterosexuals in Kenya. AIDS Res Hum Retroviruses, 30 (2), pp. 118-126. | Show Abstract | Read more

We performed a molecular phylogenetic study on HIV-1 polymerase sequences of men who have sex with men (MSM) and heterosexual patient samples in Kenya to characterize any observed HIV-1 transmission networks. HIV-1 polymerase sequences were obtained from samples in Nairobi and coastal Kenya from 84 MSM, 226 other men, and 364 women from 2005 to 2010. Using Bayesian phylogenetics, we tested whether sequences clustered by sexual orientation and geographic location. In addition, we used trait diffusion analyses to identify significant epidemiological links and to quantify the number of transmissions between risk groups. Finally, we compared 84 MSM sequences with all HIV-1 sequences available online at GenBank. Significant clustering of sequences from MSM at both coastal Kenya and Nairobi was found, with evidence of HIV-1 transmission between both locations. Although a transmission pair between a coastal MSM and woman was confirmed, no significant HIV-1 transmission was evident between MSM and the comparison population for the predominant subtype A (60%). However, a weak but significant link was evident when studying all subtypes together. GenBank comparison did not reveal other important transmission links. Our data suggest infrequent intermingling of MSM and heterosexual HIV-1 epidemics in Kenya.

Wahome E, Fegan G, Okuku HS, Mugo P, Price MA, Mwashigadi G, Thiong'o A, Graham SM, Sanders EJ. 2013. Evaluation of an empiric risk screening score to identify acute and early HIV-1 infection among MSM in Coastal Kenya. AIDS, 27 (13), pp. 2163-2166. | Show Abstract | Read more

We evaluated the University of North Carolina-Malawi Risk Screening Score (UMRSS) for detection of acute and early HIV-1 infection (AEHI) in a cohort of Kenyan MSM with approximately 8% annual HIV-1 incidence. Three components of the UMRSS (fever, diarrhea, and discordant rapid HIV tests) were also independent predictors of AEHI in our cohort. The predictive ability (area under the receiver operating characteristic curve, AUC) of the UMRSS was 0.79. A cohort-derived risk score consisting of six characteristics (fever, diarrhea, discordant rapid HIV tests, fatigue, age <30 years, and symptomatic sexually transmitted disease) had a higher AUC of 0.85. Screening for AEHI will have substantial transmission prevention benefits.

Taegtmeyer M, Davies A, Mwangome M, van der Elst EM, Graham SM, Price MA, Sanders EJ. 2013. Challenges in providing counselling to MSM in highly stigmatized contexts: results of a qualitative study from Kenya. PLoS One, 8 (6), pp. e64527. | Show Abstract | Read more

The role of men who have sex with men (MSM) in the African HIV epidemic is gaining recognition yet capacity to address the HIV prevention needs of this group is limited. HIV testing and counselling is not only a critical entry point for biomedical HIV prevention interventions, such as pre-exposure prophylaxis, rectal microbicides and early treatment initiation, but is also an opportunity for focused risk reduction counselling that can support individuals living in difficult circumstances. For prevention efforts to succeed, however, MSM need to access services and they will only do so if these are non-judgmental, informative, focused on their needs, and of clear benefit. This study aimed to understand Kenyan providers' attitudes towards and experiences with counselling MSM in a research clinic targeting this group for HIV prevention. We used in-depth interviews to explore values, attitudes and cognitive and social constructs of 13 counsellors and 3 clinicians providing services to MSM at this clinic. Service providers felt that despite their growing experience, more targeted training would have been helpful to improve their effectiveness in MSM-specific risk reduction counselling. They wanted greater familiarity with MSM in Kenya to better understand the root causes of MSM risk-taking (e.g., poverty, sex work, substance abuse, misconceptions about transmission, stigma, and sexual desire) and felt frustrated at the perceived intractability of some of their clients' issues. In addition, they identified training needs on how to question men about specific risk behaviours, improved strategies for negotiating risk reduction with counselling clients, and improved support supervision from senior counsellors. This paper describes the themes arising from these interviews and makes practical recommendations on training and support supervision systems for nascent MSM HIV prevention programmes in Africa.

Mugo PM, Duncan S, Mwaniki SW, Thiong'o AN, Gichuru E, Okuku HS, van der Elst EM, Smith AD, Graham SM, Sanders EJ. 2013. Cross-sectional survey of treatment practices for urethritis at pharmacies, private clinics and government health facilities in coastal Kenya: many missed opportunities for HIV prevention. Sex Transm Infect, 89 (7), pp. 583-589. | Show Abstract | Read more

BACKGROUND: While bacterial sexually transmitted infections (STIs) are important cofactors for HIV transmission, STI control has received little attention in recent years. The aim of this study was to assess STI treatment and HIV testing referral practices among health providers in Kenya. METHODS: In 2011 we assessed quality of case management for male urethritis at pharmacies, private clinics and government health facilities in coastal Kenya using simulated visits at pharmacies and interviews at pharmacies and health facilities. Quality was assessed using Ministry of Health guidelines. RESULTS: Twenty (77%) of 26 pharmacies, 20 (91%) of 22 private clinics and all four government facilities in the study area took part. The median (IQR) number of adult urethritis cases per week was 5 (2-10) at pharmacies, 3 (1-3) at private clinics and 5 (2-17) at government facilities. During simulated visits, 10% of pharmacies prescribed recommended antibiotics at recommended dosages and durations and, during interviews, 28% of pharmacies and 27% of health facilities prescribed recommended antibiotics at recommended dosages and durations. Most regimens were quinolone-based. HIV testing was recommended during 10% of simulated visits, 20% of pharmacy interviews and 25% of health facility interviews. CONCLUSIONS: In an area of high STI burden, most men with urethritis seek care at pharmacies and private clinics. Most providers do not comply with national guidelines and very few recommend HIV testing. In order to reduce the STI burden and mitigate HIV transmission, there is an urgent need for innovative dissemination of up-to-date guidelines and inclusion of all health providers in HIV/STI programmes.

Graham SM, Mugo P, Gichuru E, Thiong'o A, Macharia M, Okuku HS, van der Elst E, Price MA, Muraguri N, Sanders EJ. 2013. Adherence to antiretroviral therapy and clinical outcomes among young adults reporting high-risk sexual behavior, including men who have sex with men, in coastal Kenya. AIDS Behav, 17 (4), pp. 1255-1265. | Show Abstract | Read more

African men who have sex with men (MSM) face significant stigma and barriers to care. We investigated antiretroviral therapy (ART) adherence among high-risk adults, including MSM, participating in a clinic-based cohort. Survival analysis was used to compare attrition across patient groups. Differences in adherence, weight gain, and CD4 counts after ART initiation were assessed. Among 250 HIV-1-seropositive adults, including 108 MSM, 15 heterosexual men, and 127 women, patient group was not associated with attrition. Among 58 participants who were followed on ART, 40 % of MSM had less than 95 % adherence, versus 28.6 % of heterosexual men and 11.5 % of women. Although MSM gained less weight after ART initiation than women (adjusted difference -3.5 kg/year), CD4 counts did not differ. More data are needed on barriers to adherence and clinical outcomes among African MSM, to ensure that MSM can access care and derive treatment and prevention benefits from ART.

Prentice HA, Porter TR, Price MA, Cormier E, He D, Farmer PK, Kamali A, Karita E, Lakhi S, Sanders EJ et al. 2013. HLA-B*57 versus HLA-B*81 in HIV-1 infection: Slow and steady wins the race? Journal of Virology, 87 (7), pp. 4043-4051. | Show Abstract | Read more

Two human leukocyte antigen (HLA) variants, HLA-B*57 and -B*81, are consistently known as favorable host factors in human immunodeficiency virus type 1 (HIV-1)-infected Africans and African-Americans. In our analyses of prospective data from 538 recent HIV-1 seroconverters and cross-sectional data from 292 subjects with unknown duration of infection, HLA-B*57 (mostly B*57:03) and -B*81 (exclusively B*81:01) had mostly discordant associations with virologic and immunologic manifestations before antiretroviral therapy. Specifically, relatively low viral load (VL) in HLA-B*57-positive subjects (P < 0.03 in various models) did not translate to early advantage in CD4+ T-cell (CD4) counts (P > 0.37). In contrast, individuals with HLA-B*81 showed little deviation from the normal set point VL (P > 0.18) while maintaining high CD4 count during early and chronic infection (P≤0.01). These observations suggest that discordance between VL and CD4 count can occur in the presence of certain HLA alleles and that effective control of HIV-1 viremia is not always a prerequisite for favorable prognosis (delayed immunodeficiency). Of note, steady CD4 count associated with HLA-B*81 in HIV-1-infected Africans may depend on the country of origin, as observations differed slightly between subgroups enrolled in southern Africa (Zambia) and eastern Africa (Kenya, Rwanda, and Uganda). © 2013, American Society for Microbiology.

Sanders EJ, Okuku HS, Smith AD, Mwangome M, Wahome E, Fegan G, Peshu N, van der Elst EM, Price MA, McClelland RS, Graham SM. 2013. High HIV-1 incidence, correlates of HIV-1 acquisition, and high viral loads following seroconversion among MSM. AIDS, 27 (3), pp. 437-446. | Show Abstract | Read more

BACKGROUND: HIV-1 incidence estimates and correlates of HIV-1 acquisition in African MSM are largely unknown. METHODS: Since 2005, HIV-1-uninfected men who reported sex with men and women (MSMW) or sex with men exclusively (MSME) were followed at scheduled visits for collection of behavioural and clinical examination data and plasma for HIV-1 testing. Urethral or rectal secretions were collected from symptomatic men to screen for gonorrhoea. Poisson regression methods were used to estimate adjusted incidence rate ratios to explore associations between risk factors and incident HIV-1 infection. Plasma viral loads (PVLs) were assessed over 2 years following seroconversion. RESULTS: Overall HIV-1 incidence in 449 men was 8.6 [95% confidence interval (CI) 6.7-11.0] per 100 person-years. Incidence was 5.8 (95% CI 4.2-7.9) per 100 person-years among MSMW, and 35.2 (95% CI 23.8-52.1) per 100 person-years among MSME. Unprotected sex, receptive anal intercourse, exclusive sex with men, group sex, and gonorrhoea in the past 6 months were strongly associated with HIV-1 acquisition, adjusted for confounders. PVL in seroconverters was more than 4 log10 copies/ml at 230 (73.4%) of 313 visits in MSMW and 153 (75.0%) of 204 visits in MSME. CONCLUSION: HIV-1 incidence is very high among MSM in coastal Kenya, and many seroconverters maintain high PVL for up to 2 years after infection. Effective HIV-1 prevention interventions, including treatment as prevention, are urgently needed in this population.

Hassan AS, Mwaringa SM, Obonyo CA, Nabwera HM, Sanders EJ, Rinke de Wit TF, Cane PA, Berkley JA. 2013. Low prevalence of transmitted HIV type 1 drug resistance among antiretroviral-naive adults in a rural HIV clinic in Kenya. AIDS Res Hum Retroviruses, 29 (1), pp. 129-135. | Show Abstract | Read more

Low levels of HIV-1 transmitted drug resistance (TDR) have previously been reported from many parts of sub-Saharan Africa (sSA). However, recent data, mostly from urban settings, suggest an increase in the prevalence of HIV-1 TDR. Our objective was to determine the prevalence of TDR mutations among HIV-1-infected, antiretroviral (ARV)-naive adults enrolling for care in a rural HIV clinic in Kenya. Two cross-sectional studies were carried out between July 2008 and June 2010. Plasma samples from ARV-naive adults (>15 years old) at the time of registering for care after HIV diagnosis and before starting ARVs were used. A portion of the pol subgenomic region of the virus containing the protease and part of the reverse transcriptase genes was amplified and sequenced. TDR mutations were identified and interpreted using the Stanford HIV drug resistance database and the WHO list for surveillance of drug resistance strains. Overall, samples from 182 ARV-naive adults [mean age (95% CI): 34.9 (33.3-36.4) years] were successfully amplified and sequenced. Two TDR mutations to nucleoside reverse transcriptase inhibitors [n=1 (T215D)] and protease inhibitors [n=1 (M46L)] were identified, giving an overall TDR prevalence of 1.1% (95% CI: 0.1-3.9). Despite reports of an increase in the prevalence of HIV-1 TDR in some urban settings in sSA, we report a prevalence of HIV-1 TDR of less than 5% at a rural HIV clinic in coastal Kenya. Continued broader surveillance is needed to monitor the extent of TDR in sSA.

Lagace-Wiens PRS, Duncan S, Kimani J, Thiong'o A, Shafi J, McClelland S, Sanders EJ, Zhanel G, Muraguri N, Mehta SD. 2012. Emergence of fluoroquinolone resistance in Neisseria gonorrhoeae isolates from four clinics in three regions of Kenya. Sex Transm Dis, 39 (5), pp. 332-334. | Show Abstract | Read more

We have recently reported high levels of fluoroquinolone resistance in a single region of Kenya. In this article, we report high prevalence of fluoroquinolone resistance (53.2%) in Neisseria gonorrhoeae isolates from 4 clinics in 3 additional regions of Kenya. These findings highlight the need to change first-line treatment in these settings and the need to evaluate empirical management guidelines for treatment of gonococcal infection in Kenya.

Mutua G, Sanders E, Mugo P, Anzala O, Haberer JE, Bangsberg D, Barin B, Rooney JF, Mark D, Chetty P et al. 2012. Safety and adherence to intermittent pre-exposure prophylaxis (PrEP) for HIV-1 in African men who have sex with men and female sex workers. PLoS One, 7 (4), pp. e33103. | Show Abstract | Read more

BACKGROUND: Little is known about safety of and adherence to intermittent HIV PrEP regimens, which may be more feasible than daily dosing in some settings. We present safety and adherence data from the first trial of an intermittent PrEP regimen among Kenyan men who have sex with men (MSM) and female sex workers (FSW). METHODS/PRINCIPAL FINDINGS: MSM and FSW were randomized to daily oral FTC/TDF or placebo, or intermittent (Monday, Friday and within 2 hours after sex, not to exceed one dose per day) oral FTC/TDF or placebo in a 2:1:2:1 ratio; volunteers were followed monthly for 4 months. Adherence was assessed with the medication event monitoring system (MEMS). Sexual activity data were collected via daily text message (SMS) queries and timeline followback interviews with a one-month recall period. Sixty-seven men and 5 women were randomized into the study. Safety was similar among all groups. Median MEMS adherence rates were 83% [IQR: 63-92] for daily dosing and 55% [IQR:28-78] for fixed intermittent dosing (p = 0.003), while adherence to any post-coital doses was 26% [IQR:14-50]. SMS response rates were low, which may have impaired measurement of post-coital dosing adherence. Acceptability of PrEP was high, regardless of dosing regimen. CONCLUSIONS/SIGNIFICANCE: Adherence to intermittent dosing regimens, fixed doses, and in particular coitally-dependent doses, may be more difficult than adherence to daily dosing. However, intermittent dosing may still be appropriate for PrEP if intracellular drug levels, which correlate with prevention of HIV acquisition, can be attained with less than daily dosing and if barriers to adherence can be addressed. Additional drug level data, qualitative data on adherence barriers, and better methods to measure sexual activity are necessary to determine whether adherence to post-coital PrEP could be comparable to more standard regimens. TRIAL REGISTRATION: ClinicalTrials.gov NCT00971230.

Hué S, Hassan AS, Nabwera H, Sanders EJ, Pillay D, Berkley JA, Cane PA. 2012. HIV type 1 in a rural coastal town in Kenya shows multiple introductions with many subtypes and much recombination. AIDS Res Hum Retroviruses, 28 (2), pp. 220-224. | Show Abstract | Read more

The extent of HIV-1 diversity was examined among patients attending a rural district hospital in a coastal area of Kenya. The pol gene was sequenced in samples from 153 patients. Subtypes were designated using the REGA, SCUEAL, and jpHMM programs. The most common subtype was A1, followed by C and D; A2 and G were also detected. However, a large proportion of the samples was found to be recombinants, which clustered within the pure subtype branches. Phylogeographic analysis of Kilifi sequences compared with those from other regions of Africa showed that while many sequences were closely related to sequences from Kenya, others were most closely related to known sequences from other parts of Africa, including West Africa. Overall, these data indicate that there have been multiple introductions of HIV-1 into this small rural town and surroundings with ongoing diversity being generated by recombination.

Price MA, Rida W, Mwangome M, Mutua G, Middelkoop K, Roux S, Okuku HS, Bekker L-G, Anzala O, Ngugi E et al. 2012. Identifying at-risk populations in Kenya and South Africa: HIV incidence in cohorts of men who report sex with men, sex workers, and youth. J Acquir Immune Defic Syndr, 59 (2), pp. 185-193. | Show Abstract | Read more

OBJECTIVE: To identify and describe populations at risk for HIV in 3 clinical research centers in Kenya and South Africa. DESIGN: Prospective cohort study. METHODS: Volunteers reporting recent sexual activity, multiple partners, transactional sex, sex with an HIV-positive partner, or, if male, sex with men (MSM; in Kenya only) were enrolled. Sexually active minors were enrolled in South Africa only. Risk behavior, HIV testing, and clinical data were obtained at follow-up visits. RESULTS: From 2005 to 2008, 3023 volunteers were screened, 2113 enrolled, and 1834 contributed data on HIV incidence. MSM had the highest HIV incidence rate of 6.8 cases per 100 person-years [95% confidence interval (CI): 4.9 to 9.2] followed by women in Kilifi and Cape Town (2.7 cases per 100 person-years, 95% CI: 1.7 to 4.2). No seroconversions were observed in Nairobi women or men in Nairobi or Cape Town who were not MSM. In 327 MSM, predictors of HIV acquisition included report of genital ulcer (Hazard Ratio: 4.5, 95% CI: 1.7 to 11.6), not completing secondary school education (HR: 3.4, 95% CI: 1.6 to 7.2) and reporting receptive anal intercourse (HR: 8.2, 95% CI: 2.7 to 25.0). Paying for sex was inversely associated with HIV infection (HR: 0.2, 95% CI: 0.04 to 0.8). 279 (13.0%) volunteers did not return after the first visit; subsequent attrition rates ranged from 10.4 to 21.8 volunteers per 100 person-years across clinical research centers. CONCLUSIONS: Finding, enrolling, and retaining risk populations for HIV prevention trials is challenging in Africa. African MSM are not frequently engaged for research, have high HIV incidence, need urgent risk reduction counseling, and may represent a suitable population for future HIV prevention trials.

Van der Elst EM, Mbogua J, Operario D, Mutua G, Kuo C, Mugo P, Kanungi J, Singh S, Haberer J, Priddy F, Sanders EJ. 2013. High acceptability of HIV pre-exposure prophylaxis but challenges in adherence and use: qualitative insights from a phase I trial of intermittent and daily PrEP in at-risk populations in Kenya. AIDS Behav, 17 (6), pp. 2162-2172. | Show Abstract | Read more

This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.

Cited:

181

Scopus

Sullivan PS, Carballo-Diéguez A, Coates T, Goodreau SM, McGowan I, Sanders EJ, Smith A, Goswami P, Sanchez J. 2012. Successes and challenges of HIV prevention in men who have sex with men The Lancet, 380 (9839), pp. 388-399. | Show Abstract | Read more

Men who have sex with men (MSM) have been substantially affected by HIV epidemics worldwide. Epidemics in MSM are re-emerging in many high-income countries and gaining greater recognition in many low-income and middle-income countries. Better HIV prevention strategies are urgently needed. Our review of HIV prevention strategies for MSM identified several important themes. At the beginning of the epidemic, stand-alone behavioural interventions mostly aimed to reduce unprotected anal intercourse, which, although somewhat efficacious, did not reduce HIV transmission. Biomedical prevention strategies reduce the incidence of HIV infection. Delivery of barrier and biomedical interventions with coordinated behavioural and structural strategies could optimise the effectiveness of prevention. Modelling suggests that, with sufficient coverage, available interventions are sufficient to avert at least a quarter of new HIV infections in MSM in diverse countries. Scale-up of HIV prevention programmes for MSM is difficult because of homophobia and bias, suboptimum access to HIV testing and care, and financial constraints.

Cited:

47

Scopus

Hassan AS, Sakwa EM, Nabwera HM, Taegtmeyer MM, Kimutai RM, Sanders EJ, Awuondo KK, Mutinda MN, Molyneux CS, Berkley JA. 2012. Dynamics and constraints of early infant diagnosis of HIV infection in rural Kenya AIDS and Behavior, 16 (1), pp. 5-12. | Show Abstract | Read more

A cohort design was used to determine uptake and drop out of 213 HIV-exposed infants eligible for Early Infant Diagnosis (EID) of HIV. To explore service providers and care givers knowledge, attitudes and perceptions of the EID process, observations and in-depth interviews were conducted. 145 (68%) infants enrolled after 2 months of age. 139 (65%) dropped out before follow up to 18 months old. 60 (43%) drop outs occurred within 2 months of enrolment. Maternal factors associated with infant drop out were maternal loss to follow up (48 [68%] vs. 8 [20%] , P\0.001) and younger maternal age (27.2 vs. 30.1 years, P = 0.033). Service providers and caregivers had inadequate training, knowledge and understanding of EID. Poverty and lack of social support were challenges in accessing EID services. EID should be more closely aligned within PMTCT services, integrated with routine mother and child health (MCH) activities and its implementation more closely monitored. © 2011. The Author (s).

Graham SM, Holte SE, Dragavon JA, Ramko KM, Mandaliya KN, McClelland RS, Peshu NM, Sanders EJ, Krieger JN, Coombs RW. 2012. HIV-1 RNA may decline more slowly in semen than in blood following initiation of efavirenz-based antiretroviral therapy. PLoS One, 7 (8), pp. e43086. | Show Abstract | Read more

OBJECTIVES: Antiretroviral therapy (ART) decreases HIV-1 RNA levels in semen and reduces sexual transmission from HIV-1-infected men. Our objective was to study the time course and magnitude of seminal HIV-1 RNA decay after initiation of efavirenz-based ART among 13 antiretroviral-naïve Kenyan men. METHODS: HIV-1 RNA was quantified (lower limit of detection, 120 copies/mL) in blood and semen at baseline and over the first month of ART. Median log(10) HIV-1 RNA was compared at each time-point using Wilcoxon Signed Rank tests. Perelson's two-phase viral decay model and nonlinear random effects were used to compare decay rates in blood and semen. RESULTS: Median baseline HIV-1 RNA was 4.40 log(10) copies/mL in blood (range, 3.20-5.08 log(10) copies/mL) and 3.69 log(10) copies/mL in semen (range, <2.08-4.90 log(10) copies/mL). The median reduction in HIV-1 RNA by day 28 was 1.90 log(10) copies/mL in blood (range, 0.56-2.68 log(10) copies/mL) and 1.36 log(10) copies/mL in semen (range, 0-2.66 log(10) copies/mL). ART led to a decrease from baseline by day 7 in blood and day 14 in semen (p = 0.005 and p = 0.006, respectively). The initial modeled decay rate was slower in semen than in blood (p = 0.06). There was no difference in second-phase decay rates between blood and semen. CONCLUSIONS: Efavirenz-based ART reduced HIV-1 RNA levels more slowly in semen than in blood. Although this difference was of borderline significance in this small study, our observations suggest that there is suboptimal suppression of seminal HIV-1 RNA for some men in the early weeks of treatment.

Cited:

28

Scopus

Hassan AS, Fielding KL, Thuo NM, Nabwera HM, Sanders EJ, Berkley JA. 2012. Early loss to follow-up of recently diagnosed HIV-infected adults from routine pre-ART care in a rural district hospital in Kenya: a cohort study TROPICAL MEDICINE & INTERNATIONAL HEALTH, 17 (1), pp. 82-93. | Show Abstract | Read more

Objective To determine the rate and predictors of early loss to follow-up (LTFU) for recently diagnosed HIV-infected, antiretroviral therapy (ART)-ineligible adults in rural Kenya. Methods Prospective cohort study. Clients registering for HIV care between July 2008 and August 2009 were followed up for 6months. Baseline data were used to assess predictors of pre-ART LTFU (not returning for care within 2months of a scheduled appointment), LTFU before the second visit and LTFU after the second visit. Logistic regression was used to determine factors associated with LTFU before the second visit, while Cox regression was used to assess predictors of time to LTFU and LTFU after the second visit. Results Of 530 eligible clients, 178 (33.6%) were LTFU from pre-ART care (11.1/100 person-months). Of these, 96 (53.9%) were LTFU before the second visit. Distance ( > 5km vs. < 1km: adjusted hazard ratio 2.6 [1.9-3.7], P < 0.01) and marital status (married vs. single: 0.5 [0.3-0.6], P < 0.01) independently predicted pre-ART LTFU. Distance and marital status were independently associated with LTFU before the second visit, while distance, education status and seasonality showed weak evidence of predicting LTFU after the second visit. HIV disease severity did not predict pre-ART LTFU. Conclusions A third of recently diagnosed HIV-infected, ART-ineligible clients were LTFU within 6months of registration. Predictors of LTFU among ART-ineligible clients are different from those among clients on ART. These findings warrant consideration of an enhanced pre-ART care package aimed at improving retention and timely ART initiation. © 2011 Blackwell Publishing Ltd.

Hara H, Hara H, Hironaka T, Inoue M, Iida A, Shu T, Hasegawa M, Nagai Y, Falsey AR, Kamali A et al. 2011. Prevalence of specific neutralizing antibodies against Sendai virus in populations from different geographic areas: implications for AIDS vaccine development using Sendai virus vectors. Hum Vaccin, 7 (6), pp. 639-645. | Show Abstract | Read more

A Sendai virus (SeV) vector is being developed for delivery of an HIV immunogen. SeV is not known to cause disease in humans. Because it is genetically and antigenically related to human parainfluenza virus type 1 (hPIV-1), it is important to determine whether pre-existing hPIV-1 antibodies will affect immune responses elicited by a SeV vector-based vaccine. To quantify SeV neutralizing antibodies (NAb) in human serum, a sensitive virus neutralization assay was developed using a SeV vector encoding green fluorescent protein. Samples from 255 HIV-uninfected subjects from Africa, Europe, United States, and Japan, as well as from 12 confirmed hPIV-1-infected patients, were analyzed. SeV NAb titers did not vary significantly after serum was treated with receptor-destroying enzyme, indicating that non-specific hemagglutination inhibitors did not affect the assay sensitivity. A significant correlation was observed between hPIV-1 ELISA and SeV NAb titers. SeV NAb were detected in 92.5% subjects with a median titer of 60.6 and values ranging from 5.9- 11,324. The majority had titers < 1000 with 71.7% < 100 (< 5 considered negative). There was no significant difference in titer or prevalence by gender, age range or geographic origin. However, African males had a lower titer than non-Africans of either gender (p=0.007). Overall, the prevalence of SeV NAb is high and likely due to neutralization by cross-reactive hPIV-1 antibodies. Clinical trials will be needed to assess the influence of pre-existing SeV NAb on HIV-specific immune responses elicited by a SeV vaccine vector expressing HIV.

Excler J-L, Rida W, Priddy F, Gilmour J, McDermott AB, Kamali A, Anzala O, Mutua G, Sanders EJ, Koff W et al. 2011. AIDS vaccines and preexposure prophylaxis: is synergy possible? AIDS Res Hum Retroviruses, 27 (6), pp. 669-680. | Show Abstract | Read more

While the long-term goal is to develop highly effective AIDS vaccines, first generation vaccines may be only partially effective. Other HIV prevention modalities such as preexposure prophylaxis with antiretrovirals (PrEP) may have limited efficacy as well. The combined administration of vaccine and PrEP (VAXPREP), however, may have a synergistic effect leading to an overall benefit that is greater than the sum of the individual effects. We propose two test-of-concept trial designs for an AIDS vaccine plus oral or topical ARV. In one design, evidence that PrEP reduces the risk of HIV acquisition is assumed to justify offering it to all participants. A two-arm study comparing PrEP alone to VAXPREP is proposed in which 30 to 60 incident infections are observed to assess the additional benefit of vaccination on risk of infection and setpoint viral load. The demonstrated superiority of VAXPREP does not imply vaccine alone is efficacious. Similarly, the lack of superiority does not imply vaccine alone is ineffective, as antagonism could exist between vaccine and PrEP. In the other design, PrEP is assumed not to be in general use. A 2 × 2 factorial design is proposed in which high-risk individuals are randomized to one of four arms: placebo vaccine given with placebo PrEP, placebo vaccine given with PrEP, vaccine given with placebo PrEP, or VAXPREP. Between 60 and 210 infections are required to detect a benefit of vaccination with or without PrEP on risk of HIV acquisition or setpoint viral load, with fewer infections needed when synergy is present.

Nyiro JU, Sanders EJ, Ngetsa C, Wale S, Awuondo K, Bukusi E, Price MA, Amornkul PN, Nokes DJ. 2011. Seroprevalence, predictors and estimated incidence of maternal and neonatal Herpes Simplex Virus type 2 infection in semi-urban women in Kilifi, Kenya. BMC Infect Dis, 11 (1), pp. 155. | Show Abstract | Read more

BACKGROUND: Herpes Simplex Virus type 2 (HSV-2) has public health importance as a leading cause of genital ulcers, a co-factor in HIV-1 acquisition and transmission and as a cause of neonatal herpes infections. Little is known of its epidemiology and burden in Coastal Kenya. METHODS: We screened plasma samples for HSV-2 infection from 826 women aged 15-34 years who participated in an HIV-1 survey in Kilifi in 2004. The sample comprised 563 women selected randomly from a demographic surveillance system (DSS) and 263 women who presented for voluntary counseling and testing (VCT). Predictors for HSV-2 seropositivity were determined using multivariate logistic regression. The incidence of HSV-2 infection and risk of neonatal herpes were estimated by a simple catalytic model fitted to age-seroprevalence data. RESULTS: HSV-2 prevalence was 32% in the DSS recruits vs. 44% in the VCT recruits (P < 0.001), while, HIV-1 prevalence was 8% in the DSS recruits vs. 12% in the VCT recruits (P = 0.12). Independent risk factors for HSV-2 infection in all women were: older age (30-34 years; odds ratio (OR) 10.5, 95% confidence interval (CI): 5.2 - 21.0), recruitment from VCT (OR 1.5, 95% CI: 1.1 - 2.1), history of genital ulcers (OR 1.7, 95% CI: 1.2 - 2.3) and HIV infection (OR 2.7, 95% CI: 1.6-4.6). Education beyond primary (OR 0.7, 95% CI: 0.5 - 0.9) was inversely associated with HSV-2 infection. In the DSS sample, HSV-2 incidence was estimated at 4 cases (95% CI: 3.3 - 4.4) per 100 women per year, 17 cases (95% CI: 16-18) per 1,000 pregnancies per year and 33 neonatal cases (95% CI: 31-36) per 100,000 births per year. CONCLUSIONS: HSV-2 transmission is rapid following the onset of sexual activity and likely to result in a significant burden of genital ulcer disease. Nevertheless, the burden of neonatal HSV-2 can be predicted to be low. Educating young women about HSV-2 infection may help in reducing its burden in this semi-urban population.

Sanders EJ, Wahome E, Mwangome M, Thiong'o AN, Okuku HS, Price MA, Wamuyu L, Macharia M, McClelland RS, Graham SM. 2011. Most adults seek urgent healthcare when acquiring HIV-1 and are frequently treated for malaria in coastal Kenya. AIDS, 25 (9), pp. 1219-1224. | Show Abstract | Read more

BACKGROUND: Acute HIV-1 infection (AHI) may present with symptoms for which urgent healthcare is sought. However, little is known about healthcare seeking around the time of HIV-1 seroconversion in sub-Saharan Africa. METHODS: Review of clinical, counselling, treatment and laboratory records of previously HIV-1 seronegative at-risk adults, followed at monthly or 3-monthly visits, who seroconverted and enrolled in an AHI cohort. All HIV-seronegative plasma samples were tested for p24 antigen (p24) and stored preseroconversion samples for HIV-1 RNA (RNA). Factors associated with malaria treatment while acquiring HIV-1 were evaluated in multiple logistic regression. RESULTS: Sixty men and 12 women (95% of 75 seroconverters) were evaluated, including 43 (60%) with either p24-positive or RNA-positive or HIV-1 discordant rapid antibodies prior to seroconversion. Prior to diagnosis, 54 patients (75%) reported fever and 50 (69%) sought urgent care for symptomatic illness, including 23 (32%) who sought care in a nonresearch setting. Twenty-nine patients (40%) received presumptive malaria treatment. Only 24% of febrile patients were tested for malaria parasites. All documented smear results were negative. Malaria treatment was strongly associated with fever [adjusted odds ratio (aOR): 46, 95% confidence interval (CI): 3-725] and nonresearch setting (aOR: 5, 95% CI: 3-64). AHI was suspected in six (12%) patients who presented for urgent care during research evaluation. CONCLUSIONS: The majority of adults with AHI seek urgent healthcare. These individuals are often presumptively treated for malaria. Improved recognition of AHI in adults presenting for care may offer opportunities for optimizing HIV prevention strategies.

Duncan S, Thiong'o AN, Macharia M, Wamuyu L, Mwarumba S, Mvera B, Smith AD, Morpeth S, Graham SM, Sanders EJ. 2011. High prevalence of quinolone resistance in Neisseria gonorrhoeae in coastal Kenya. Sex Transm Infect, 87 (3), pp. 231. | Read more

Papo JK, Bauni EK, Sanders EJ, Brocklehurst P, Jaffe HW. 2011. Exploring the condom gap: is supply or demand the limiting factor - condom access and use in an urban and a rural setting in Kilifi district, Kenya. AIDS, 25 (2), pp. 247-255. | Show Abstract | Read more

OBJECTIVE: to explore the extent of the condom gap, investigating the relative roles of supply-side and demand-side factors in determining condom use. DESIGN: GPS mapping of condom outlets, and population-based survey. METHODS: an urban and a rural site were selected within the Epidemiological and Demographic Surveillance Site in Kilifi district, Kenya. Potential condom outlets (n = 281) were mapped and surveyed, and questionnaires on condom access and use (n = 630) were administered to a random sample of men and women aged 15-49. Multivariate logistic regression was performed to assess the relative roles of supply-side and demand-side barriers on condom use. RESULTS: the median straight-line distance to free condoms was 18-fold higher in the rural versus urban site. Among sexually active respondents, 42% had ever used a condom, and 23% had used a condom over the past 12 months, with lower levels among rural versus urban respondents (P < 0.05). The mean number of condoms used was 2.2/person per year among all sexually active individuals (condom users and nonusers), amounting to 8.2% protected sex acts/person per year. The adjusted odds of condom use (past 12 months) were 8.1 times greater among individuals experiencing no supply-side or demand-side barriers, compared with individuals experiencing both types of barriers. Despite low levels of usage and the presence of supply-side and demand-side barriers, reported unmet need for condoms was low. CONCLUSIONS: there is an urgent need for renewed condom promotion efforts aimed at building demand, in addition to improving physical access, in resource-limited settings with generalized HIV epidemics in sub-Saharan Africa.

Tang J, Cormier E, Gilmour J, Price MA, Prentice HA, Song W, Kamali A, Karita E, Lakhi S, Sanders EJ et al. 2011. Human leukocyte antigen variants B*44 and B*57 are consistently favorable during two distinct phases of primary HIV-1 infection in sub-Saharan Africans with several viral subtypes. J Virol, 85 (17), pp. 8894-8902. | Show Abstract | Read more

As part of an ongoing study of early human immunodeficiency virus type 1 (HIV-1) infection in sub-Saharan African countries, we have identified 134 seroconverters (SCs) with distinct acute-phase (peak) and early chronic-phase (set-point) viremias. SCs with class I human leukocyte antigen (HLA) variants B*44 and B*57 had much lower peak viral loads (VLs) than SCs without these variants (adjusted linear regression beta values of -1.08 ± 0.26 log(10) [mean ± standard error] and -0.83 ± 0.27 log(10), respectively; P < 0.005 for both), after accounting for several nongenetic factors, including gender, age at estimated date of infection, duration of infection, and country of origin. These findings were confirmed by alternative models in which major viral subtypes (A1, C, and others) in the same SCs replaced country of origin as a covariate (P ≤ 0.03). Both B*44 and B*57 were also highly favorable (P ≤ 0.03) in analyses of set-point VLs. Moreover, B*44 was associated with relatively high CD4(+) T-cell counts during early chronic infection (P = 0.02). Thus, at least two common HLA-B variants showed strong influences on acute-phase as well as early chronic-phase VL, regardless of the infecting viral subtype. If confirmed, the identification of B*44 as another favorable marker in primary HIV-1 infection should help dissect mechanisms of early immune protection against HIV-1 infection.

Okuku HS, Sanders EJ, Nyiro J, Ngetsa C, Ohuma E, McClelland RS, Price MA, Graham SM. 2011. Factors associated with herpes simplex virus type 2 incidence in a cohort of human immunodeficiency virus type 1-seronegative Kenyan men and women reporting high-risk sexual behavior. Sex Transm Dis, 38 (9), pp. 837-844. | Show Abstract | Read more

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is an important cause of genital ulcers and can increase the risk for human immunodeficiency virus type 1 (HIV-1) transmission. Our objective was to determine the incidence and correlates of HSV-2 infection in HIV-1-seronegative Kenyan men reporting high-risk sexual behavior, compared with high-risk HIV-1-seronegative women in the same community. METHODS: Cohort participants were screened for prevalent HIV-1 infection. HIV-1-uninfected participants had regularly scheduled follow-up visits, with HIV counseling and testing and collection of demographic and behavioral data. Archived blood samples were tested for HSV-2. RESULTS: HSV-2 prevalence was 22.0% in men and 50.8% in women (P < 0.001). HSV-2 incidence in men was 9.0 per 100 person-years, and was associated with incident HIV-1 infection (adjusted incidence rate ratio [aIRR], 3.9; 95% confidence interval [CI], 1.3-12.4). Use of soap for genital washing was protective (aIRR, 0.3; 95% CI, 0.1-0.8). Receptive anal intercourse had a borderline association with HSV-2 acquisition in men (aIRR, 2.0; 95% CI, 1.0-4.1; P = 0.057), and weakened the association with incident HIV-1. Among women, HSV-2 incidence was 22.1 per 100 person-years (P < 0.001 compared with incidence in men), and was associated with incident HIV-1 infection (aIRR, 8.9; 95% CI, 3.6-21.8) and vaginal washing with soap (aIRR, 1.9; 95% CI, 1.0-3.4). CONCLUSIONS: HSV-2 incidence in these men and women is among the highest reported, and is associated with HIV-1 acquisition. Although vaginal washing with soap may increase HSV-2 risk in women, genital hygiene may be protective in men.

Graham SM, Krieger JN, Githua PLM, Wamuyu LW, Wale S, Ramko KM, Dragavon JA, Muller CH, Holte SE, Mandaliya KN et al. 2011. Post-prostatic massage fluid/urine as an alternative to semen for studying male genitourinary HIV-1 shedding. Sex Transm Infect, 87 (3), pp. 232-237. | Show Abstract | Read more

OBJECTIVES: Genitourinary tract samples are required to investigate male HIV-1 infectivity. Because semen collection is often impractical, the acceptability, feasibility and validity of post-prostatic massage fluid/urine (post-PMF/U) was evaluated for studying male genitourinary HIV-1 shedding. METHODS: HIV-1-seropositive men were evaluated after 48 h of sexual abstinence. At each visit, a clinician performed prostatic massage, then post-PMF/U and blood were collected. Participants provided semen specimens 1 week later. An audio computer-assisted self-interview (ACASI) administered after each specimen collection evaluated acceptability, adherence to instructions and recent genitourinary symptoms. HIV-1 RNA was quantified using a real-time PCR assay. Detection and quantitation of HIV-1 RNA and stability over visits were compared for semen, post-PMF/U and blood. RESULTS: Post-PMF/U was successfully obtained at 106 visits (64%) and semen at 136 visits (81%, p<0.001). In ACASI, discomfort was rated higher for post-PMF/U collection (p=0.003), but there was no significant difference in acceptability. Detection of HIV-1 RNA in post-PMF/U was associated with detection in semen (p=0.02). Semen and post-PMF/U HIV-1-RNA levels were correlated (ρ=0.657, p<0.001). Concordance of results at repeat visits was 78.9% for post-PMF/U (κ=0.519, p=0.02) and 89.5% for both blood and semen (κ=0.774, p=0.001). CONCLUSIONS: Although semen collections were more successful, both post-PMF/U and semen collections were acceptable to many participants. HIV-1 RNA detection and levels were closely associated in semen and post-PMF/U, and results were relatively stable across visits. To assess male HIV-1 infectivity, post-PMF/U may represent a valid alternative when semen cannot be obtained.

Price MA, Wallis CL, Lakhi S, Karita E, Kamali A, Anzala O, Sanders EJ, Bekker L-G, Twesigye R, Hunter E et al. 2011. Transmitted HIV type 1 drug resistance among individuals with recent HIV infection in East and Southern Africa. AIDS Res Hum Retroviruses, 27 (1), pp. 5-12. | Show Abstract | Read more

To characterize WHO-defined transmitted HIV drug resistance mutation (TDRM) data from recently HIV-infected African volunteers, we sequenced HIV (pol) and evaluated for TDRM the earliest available specimens from ARV-naive volunteers diagnosed within 1 year of their estimated date of infection at eight research centers in sub-Saharan Africa. TDRMs were detected in 19/408 (5%) volunteers. The prevalence of TDRMs varied by research center, from 5/26 (19%) in Entebbe, 6/78 (8%) in Kigali, 2/49 (4%) in Kilifi, to 3/106 (3%) in Lusaka. One of five volunteers from Cape Town (20%) had TDRMs. Despite small numbers, our data suggest an increase in DRMs by year of infection in Zambia (p = 0.004). The prevalence observed in Entebbe was high across the entire study. ARV history data from 12 (63%) HIV-infected sexual partners were available; 3 reported ARV use prior to transmission. Among four partners with sequence data available, transmission linkage was confirmed and two had the same TDRMs as the newly infected volunteer (both K103N). As ARV therapy continues to increase in availability throughout Africa, monitoring incident virus strains for the presence of TDRMs should be a priority. Early HIV infection cohorts provide an excellent and important platform to monitor the development of TDRMs to inform treatment guidelines, drug choices, and strategies for secondary prevention of TDRM transmission.

Sanders EJ, Thiong'o AN, Okuku HS, Mwambi J, Priddy F, Shafi J, de Vries H, McClelland RS, Graham SM. 2010. High prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae infections among HIV-1 negative men who have sex with men in coastal Kenya. Sex Transm Infect, 86 (6), pp. 440-441. | Show Abstract | Read more

OBJECTIVES: To assess the burden of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) in high-risk HIV-1 negative men who have sex with men (MSM) in Africa. METHODS: Before the start of a pre-exposure prophylaxis trial, HIV-1 negative volunteers were screened for sexually transmitted infection (STI) including CT and NG, using a highly sensitive and specific nucleic acid amplification test. Samples positive for CT by Aptima testing, were evaluated for the presence of lymphogranuloma venereum (LGV) serovars using an in-house PCR assay. All men were asked to submit a urine specimen, and all had a rectal swab collected by a clinician. Men were asked if they had dysuria, urethral or rectal discharge, or rectal pain. RESULTS: 43 HIV-1 negative MSM were screened, of whom 13 reported sex with men only; the majority (27/43) reported sex work. One volunteer had dysuria and another, rectal pain. Eleven MSM (26%, 95% CI 14% to 41%) had infections with either or both pathogens. Homosexual men had a higher prevalence of any infection than bisexual men (46% vs 17%, p=0.04), and all cases of rectal infections, including one with CT, two with NG and two with CT/NG co-infection. All patients with CT were negative for LGV. One patient with a rectal NG infection reported rectal pain. CONCLUSIONS: A remarkably high burden of STI infection was found among HIV-1 negative MSM. Most (12/13) infections, including three of four rectal NG infections, were subclinical. These findings suggest that high-risk MSM will benefit from effective STI screening in Kenya.

Tensou B, Araya T, Telake DS, Byass P, Berhane Y, Kebebew T, Sanders EJ, Reniers G. 2010. Evaluating the InterVA model for determining AIDS mortality from verbal autopsies in the adult population of Addis Ababa. Trop Med Int Health, 15 (5), pp. 547-553. | Show Abstract | Read more

OBJECTIVE: To evaluate the performance of a verbal autopsy (VA) expert algorithm (the InterVA model) for diagnosing AIDS mortality against a reference standard from hospital records that include HIV serostatus information in Addis Ababa, Ethiopia. METHODS: Verbal autopsies were conducted for 193 individuals who visited a hospital under surveillance during terminal illness. Decedent admission diagnosis and HIV serostatus information are used to construct two reference standards (AIDS vs. other causes of death and TB/AIDS vs. other causes). The InterVA model is used to interpret the VA interviews; and the sensitivity, specificity and cause-specific mortality fractions are calculated as indicators of the diagnostic accuracy of the InterVA model. RESULTS: The sensitivity and specificity of the InterVA model for diagnosing AIDS are 0.82 (95% CI: 0.74-0.89) and 0.76 (95% CI: 0.64-0.86), respectively. The sensitivity and specificity for TB/AIDS are 0.91 (95% CI: 0.85-0.96) and 0.78 (95% CI: 0.63-0.89), respectively. The AIDS-specific mortality fraction estimated by the model is 61.7% (95% CI: 54-69%), which is close to 64.7% (95% CI: 57-72%) in the reference standard. The TB/AIDS mortality fraction estimated by the model is 73.6% (95% CI: 67-80%), compared to 74.1% (95% CI: 68-81%) in the reference standard. CONCLUSION: The InterVA model is an easy to use and cheap alternative to physician review for assessing AIDS mortality in populations without vital registration and medical certification of causes of death. The model seems to perform better when TB and AIDS are combined, but the sample is too small to statistically confirm that.

Wallis CL, Papathanasopoulos MA, Lakhi S, Karita E, Kamali A, Kaleebu P, Sanders E, Anzala O, Bekker L-G, Stevens G et al. 2010. Affordable in-house antiretroviral drug resistance assay with good performance in non-subtype B HIV-1. J Virol Methods, 163 (2), pp. 505-508. | Show Abstract | Read more

The introduction of antiretroviral (ARV) therapy in resource-poor settings is effective in suppressing HIV-1 replication and prolonging life of infected individuals. This has led to a demand for affordable HIV-1 drug resistance assays, since treatment failure due to development of drug resistance is common. This study developed and evaluated an affordable "in-house" genotyping assay to monitor HIV-1 drug resistance in Africa, particularly South Africa. An "in-house" assay using automated RNA extraction, and subtype C specific PCR and sequencing primers was developed and successfully evaluated 396 patient samples (viral load ranges 1000-1.6 million RNA copies/ml). The "in-house" assay was validated by comparing sequence data and drug resistance profiles from 90 patient and 10 external quality control samples to data from the ViroSeq HIV-1 Genotyping kit. The "in-house" assay was more efficient, amplifying all 100 samples, compared to 91 samples using Viroseq. The "in house" sequences were 99.2% homologous to the ViroSeq sequences, and identical drug resistance mutation profiles were observed in 96 samples. Furthermore, the "in-house" assay genotyped 260 of 295 samples from seven African sites, where 47% were non-subtype C. Overall, the newly validated "in-house" drug resistance assay is suited for use in Africa as it overcomes the obstacle of subtype diversity.

Tovanabutra S, Sanders EJ, Graham SM, Mwangome M, Peshu N, McClelland RS, Muhaari A, Crossler J, Price MA, Gilmour J et al. 2010. Evaluation of HIV type 1 strains in men having sex with men and in female sex workers in Mombasa, Kenya. AIDS Res Hum Retroviruses, 26 (2), pp. 123-131. | Show Abstract | Read more

We compared HIV-1 strains in incident and prevalent infections in a cohort of men having sex with men (MSM) and female sex workers (FSW) near Mombasa, Kenya and conducted a cross-sectional study of viral isolates from a sample of HIV-1-infected MSM and FSW in Kilifi, Coast Province, Kenya. RNA extracted from plasma of 13 MSM, 9 FSW, and one heterosexual male was amplified by nested RT-PCR and the products were directly sequenced. HIV-1 strains from 21 individuals were characterized with one or more complete genome sequences, and two were sequenced in the Nef gene. The envelope quasispecies was also studied in one individual. Among MSM, eight strains were subtype A and five were recombinant. There were two epidemiologically linked pairs of sequences; one pair was subtype A and the other pair was a complex AA2CD recombinant of identical structure. Another MSM was dually infected with DG recombinant strains of related, but nonidentical, structure. MSM also harbored AC and AD recombinant strains. The FSW harbored seven subtype A strains, an AD recombinant, and an AA2D strain related to CRF16_A2D. The one heterosexual male studied had a subtype A infection. This MSM epidemic in Kenya appears to be of local origin, harboring many strains typical of the broader Kenyan epidemic. Characteristics of a close social network were identified, with extended chains of transmission, novel recombinant strains possibly generated within the network, and a relatively high proportion of recombinant and dual infections.

Smith AD, Tapsoba P, Peshu N, Sanders EJ, Jaffe HW. 2009. Men who have sex with men and HIV/AIDS in sub-Saharan Africa. Lancet, 374 (9687), pp. 416-422. | Show Abstract | Read more

Globally, men who have sex with men (MSM) continue to bear a high burden of HIV infection. In sub-Saharan Africa, same-sex behaviours have been largely neglected by HIV research up to now. The results from recent studies, however, indicate the widespread existence of MSM groups across Africa, and high rates of HIV infection, HIV risk behaviour, and evidence of behavioural links between MSM and heterosexual networks have been reported. Yet most African MSM have no safe access to relevant HIV/AIDS information and services, and many African states have not begun to recognise or address the needs of these men in the context of national HIV/AIDS prevention and control programmes. The HIV/AIDS community now has considerable challenges in clarifying and addressing the needs of MSM in sub-Saharan Africa; homosexuality is illegal in most countries, and political and social hostility are endemic. An effective response to HIV/AIDS requires improved strategic information about all risk groups, including MSM. The belated response to MSM with HIV infection needs rapid and sustained national and international commitment to the development of appropriate interventions and action to reduce structural and social barriers to make these accessible.

Reniers G, Araya T, Berhane Y, Davey G, Sanders EJ. 2009. Implications of the HIV testing protocol for refusal bias in seroprevalence surveys. BMC Public Health, 9 (1), pp. 163. | Show Abstract | Read more

BACKGROUND: HIV serosurveys have become important sources of HIV prevalence estimates, but these estimates may be biased because of refusals and other forms of non-response. We investigate the effect of the post-test counseling study protocol on bias due to the refusal to be tested. METHODS: Data come from a nine-month prospective study of hospital admissions in Addis Ababa during which patients were approached for an HIV test. Patients had the choice between three consent levels: testing and post-test counseling (including the return of HIV test results), testing without post-test counseling, and total refusal. For all patients, information was collected on basic sociodemographic background characteristics as well as admission diagnosis. The three consent levels are used to mimic refusal bias in serosurveys with different post-test counseling study protocols. We first investigate the covariates of consent for testing. Second, we quantify refusal bias in HIV prevalence estimates using Heckman regression models that account for sample selection. RESULTS: Refusal to be tested positively correlates with admission diagnosis (and thus HIV status), but the magnitude of refusal bias in HIV prevalence surveys depends on the study protocol. Bias is larger when post-test counseling and the return of HIV test results is a prerequisite of study participation (compared to a protocol where test results are not returned to study participants, or, where there is an explicit provision for respondents to forego post-test counseling). We also find that consent for testing increased following the introduction of antiretroviral therapy in Ethiopia. Other covariates of refusal are age (non-linear effect), gender (higher refusal rates in men), marital status (lowest refusal rates in singles), educational status (refusal rate increases with educational attainment), and counselor. CONCLUSION: The protocol for post-test counseling and the return of HIV test results to study participants is an important consideration in HIV prevalence surveys that wish to minimize refusal bias. The availability of ART is likely to reduce refusal rates.

Reniers G, Araya T, Davey G, Nagelkerke N, Berhane Y, Coutinho R, Sanders EJ. 2009. Steep declines in population-level AIDS mortality following the introduction of antiretroviral therapy in Addis Ababa, Ethiopia. AIDS, 23 (4), pp. 511-518. | Show Abstract | Read more

OBJECTIVES: Assessments of population-level effects of antiretroviral therapy (ART) programmes in Africa are rare. We use data from burial sites to estimate trends in adult AIDS mortality and the mitigating effects of ART in Addis Ababa. ART has been available since 2003, and for free since 2005. METHODS: To substitute for deficient vital registration, we use surveillance of burials at all cemeteries. We present trends in all-cause mortality, and estimate AIDS mortality (ages 20-64 years) from lay reports of causes of death. These lay reports are first used as a diagnostic test for the true cause of death. As reference standard, we use the cause of death established via verbal autopsy interviews conducted in 2004. The positive predictive value and sensitivity are subsequently used as anchors to estimate the number of AIDS deaths for the period 2001-2007. Estimates are compared with Spectrum projections. RESULTS: Between 2001 and 2005, the number of AIDS deaths declined by 21.9 and 9.3% for men and women, respectively. Between 2005 and 2007, the number of AIDS deaths declined by 38.2 for men and 42.9% for women. Compared with the expected number in the absence of ART, the reduction in AIDS deaths in 2007 is estimated to be between 56.8 and 63.3%, depending on the coverage of the burial surveillance. CONCLUSION: Five years into the ART programme, adult AIDS mortality has been reduced by more than half. Following the free provision of ART in 2005, the decline accelerated and became more sex balanced. Substantial AIDS mortality, however, persists.

Karita E, Ketter N, Price MA, Kayitenkore K, Kaleebu P, Nanvubya A, Anzala O, Jaoko W, Mutua G, Ruzagira E et al. 2009. CLSI-derived hematology and biochemistry reference intervals for healthy adults in eastern and southern Africa. PLoS One, 4 (2), pp. e4401. | Show Abstract | Read more

BACKGROUND: Clinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial. METHODS AND FINDINGS: Equal proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S. -derived DAIDS AE grading criteria, we observed 774 (35.3%) volunteers with grade one or higher results; 314 (14.9%) had elevated total bilirubin, and 201 (9.6%) had low neutrophil counts. These otherwise healthy volunteers would be excluded or would require special exemption to participate in many clinical trials. CONCLUSIONS: To accelerate clinical trials in Africa, and to improve their scientific validity, locally appropriate reference ranges should be used. This study provides ranges that will inform inclusion criteria and evaluation of adverse events for studies in these regions of Africa.

van der Elst EM, Okuku HS, Nakamya P, Muhaari A, Davies A, McClelland RS, Price MA, Smith AD, Graham SM, Sanders EJ. 2009. Is audio computer-assisted self-interview (ACASI) useful in risk behaviour assessment of female and male sex workers, Mombasa, Kenya? PLoS One, 4 (5), pp. e5340. | Show Abstract | Read more

BACKGROUND: Audio computer-assisted self-interview (ACASI) may elicit more frequent reporting of socially sensitive behaviours than face-to-face (FtF)-interview. However, no study compared responses to both methods in female and male sex workers (FSW; MSW) in Africa. METHODOLOGY/PRINCIPAL FINDINGS: We sequentially enrolled adults recruited for an HIV-1 intervention trial into a comparative study of ACASI and FtF-interview, in a clinic near Mombasa, Kenya. Feasibility and acceptability of ACASI, and a comparative analysis of enrolment responses between ACASI and FtF on an identical risk assessment questionnaire were evaluated. In total, 139 women and 259 men, 81% of eligible cohort participants, completed both interviews. ACASI captured a higher median number of regular (2 vs. 1, p<0.001, both genders) and casual partners in the last week (3 vs. 2, p = 0.04 in women; 2 vs. 1, p<0.001 in men). Group sex (21.6 vs. 13.5%, p<0.001, in men), intravenous drug use (IDU; 10.8 vs. 2.3%, p<0.001 in men; 4.4 vs. 0%, p = 0.03 in women), and rape (8.9 vs. 3.9%, p = 0.002, in men) were reported more frequently in ACASI. A surprisingly high number of women reported in ACASI that they had paid for sex (49.3 vs. 5.8%, p<0.001). Behaviours for recruitment (i.e. anal sex, sex work, sex between males) were reported less frequently in ACASI. The majority of women (79.2%) and men (69.7%) felt that answers given in ACASI were more honest. Volunteers who were not able to take ACASI (84 men, and 37 women) mostly lacked reading skills. CONCLUSIONS/SIGNIFICANCE: About 1 in 5 cohort participants was not able to complete ACASI, mostly for lack of reading skills. Participants who completed ACASI were more likely to report IDU, rape, group sex, and payment for sex by women than when asked in FtF interview. ACASI appears to be a useful tool for high risk behaviour assessments in the African context.

Anzala O, Sanders EJ, Kamali A, Katende M, Mutua GN, Ruzagira E, Stevens G, Simek M, Price M. 2008. Sensitivity and specificity of HIV rapid tests used for research and voluntary counselling and testing. East Afr Med J, 85 (10), pp. 500-504. | Show Abstract

BACKGROUND: HIV rapid tests (RT) are a quick and non-technically demanding means to perform HIV voluntary counselling and testing (VCT) but understanding their limitations is vital to delivering quality VCT. OBJECTIVE: To determine the sensitivity and specificity of HIV rapid tests used for research and voluntary counselling and testing at four sites in East Africa. DESIGN: Cross-sectional study. SETTING: Masaka District, Uganda; a sugar plantation in Kakira, Uganda; Coastal Villages in the Kilifi District of Kenya; and the Urban slum of Kangemi located West of Nairobi, Kenya. SUBJECTS: Six thousands two hundred and fifty five consenting volunteers were enrolled into the study, and 675 prevalent HIV infections were identified. RESULTS: The RT sensitivity tended to be high for all assays at all sites (97.63-100%) with the exception of the Uni-Gold assay (90.24% in Kangemi, 96.58% in Kilifi). Twenty four RT results were recorded as 'weak positives', 22 (92%) of which were negative by ELISA. There was a high rate of RT false positives in Uganda (positive predictive values ranging from 45.70% to 86.62%). CONCLUSIONS: The sensitivity and specificity of the RT varied significantly across sites. The rate of RT misclassification in Uganda suggests that a multiple test algorithm may be preferable to a single test as screener for HIV VCT.

Grijsen ML, Graham SM, Mwangome M, Githua P, Mutimba S, Wamuyu L, Okuku H, Price MA, McClelland RS, Smith AD, Sanders EJ. 2008. Screening for genital and anorectal sexually transmitted infections in HIV prevention trials in Africa. Sex Transm Infect, 84 (5), pp. 364-370. | Show Abstract | Read more

OBJECTIVES: To demonstrate the value of routine, basic sexually transmitted infection (STI) screening at enrolment into an HIV-1 vaccine feasibility cohort study and to highlight the importance of soliciting a history of receptive anal intercourse (RAI) in adults identified as "high risk". METHODS: Routine STI screening was offered to adults at high risk of HIV-1 upon enrolment into a cohort study in preparation for HIV-1 vaccine trials. Risk behaviours and STI prevalence were summarised and the value of microscopy assessed. Associations between prevalent HIV-1 infection and RAI or prevalent STI were evaluated with multiple logistic regression. RESULTS: Participants had a high burden of untreated STI. Symptom-directed management would have missed 67% of urethritis cases in men and 59% of cervicitis cases in women. RAI was reported by 36% of male and 18% of female participants. RAI was strongly associated with HIV-1 in men (adjusted odds ratio (aOR) 3.8; 95% CI 2.0 to 6.9) and independently associated with syphilis in women (aOR 12.9; 95% CI 3.4 to 48.7). CONCLUSIONS: High-risk adults recruited for HIV-1 prevention trials carry a high STI burden. Symptom-directed treatment may miss many cases and simple laboratory-based screening can be done with little cost. Risk assessment should include questions about anal intercourse and whether condoms were used. STI screening, including specific assessment for anorectal disease, should be offered in African research settings recruiting participants at high risk of HIV-1 acquisition.

van Griensven F, Sanders EJ. 2008. Understanding HIV risks among men who have sex with men in Africa. Sex Transm Dis, 35 (4), pp. 355-356. | Read more

Walson JL, Otieno PA, Mbuchi M, Richardson BA, Lohman-Payne B, Macharia SW, Overbaugh J, Berkley J, Sanders EJ, Chung MH, John-Stewart GC. 2008. Albendazole treatment of HIV-1 and helminth co-infection: a randomized, double-blind, placebo-controlled trial. AIDS, 22 (13), pp. 1601-1609. | Show Abstract | Read more

OBJECTIVE: Several co-infections have been shown to impact the progression of HIV-1 infection. We sought to determine if treatment of helminth co-infection in HIV-1-infected adults impacted markers of HIV-1 disease progression. DESIGN: To date, there have been no randomized trials to examine the effects of soil-transmitted helminth eradication on markers of HIV-1 progression. METHODS: A randomized, double-blind, placebo-controlled trial of albendazole (400 mg daily for 3 days) in antiretroviral-naive HIV-1-infected adults (CD4 cell count >200 cells/microl) with soil-transmitted helminth infection was conducted at 10 sites in Kenya (ClinicalTrials.gov NCT00130910). CD4 and plasma HIV-1 RNA levels at 12 weeks following randomization were compared in the trial arms using linear regression, adjusting for baseline values. RESULTS: Of 1551 HIV-1-infected individuals screened for helminth infection, 299 were helminth infected. Two hundred and thirty-four adults were enrolled and underwent randomization and 208 individuals were included in intent-to-treat analyses. Mean CD4 cell count was 557 cells/microl and mean plasma viral load was 4.75 log10 copies/ml at enrollment. Albendazole therapy resulted in significantly higher CD4 cell counts among individuals with Ascaris lumbricoides infection after 12 weeks of follow-up (+109 cells/microl; 95% confidence interval +38.9 to +179.0, P = 0.003) and a trend for 0.54 log10 lower HIV-1 RNA levels (P = 0.09). These effects were not seen with treatment of other species of soil-transmitted helminths. CONCLUSION: Treatment of A. lumbricoides with albendazole in HIV-1-coinfected adults resulted in significantly increased CD4 cell counts during 3-month follow-up. Given the high prevalence of A. lumbricoides infection worldwide, deworming may be an important potential strategy to delay HIV-1 progression.

Stevens W, Kamali A, Karita E, Anzala O, Sanders EJ, Jaoko W, Kaleebu P, Mulenga J, Dally L, Fast P et al. 2008. Baseline morbidity in 2,990 adult African volunteers recruited to characterize laboratory reference intervals for future HIV vaccine clinical trials. PLoS One, 3 (4), pp. e2043. | Show Abstract | Read more

BACKGROUND: An understanding of the health of potential volunteers in Africa is essential for the safe and efficient conduct of clinical trials, particularly for trials of preventive technologies such as vaccines that enroll healthy individuals. Clinical safety laboratory values used for screening, enrolment and follow-up of African clinical trial volunteers have largely been based on values derived from industrialized countries in Europe and North America. This report describes baseline morbidity during recruitment for a multi-center, African laboratory reference intervals study. METHODS: Asymptomatic persons, aged 18-60 years, were invited to participate in a cross-sectional study at seven sites (Kigali, Rwanda; Masaka and Entebbe, Uganda; Kangemi, Kenyatta National Hospital and Kilifi, Kenya; and Lusaka, Zambia). Gender equivalency was by design. Individuals who were acutely ill, pregnant, menstruating, or had significant clinical findings were not enrolled. Each volunteer provided blood for hematology, immunology, and biochemistry parameters and urine for urinalysis. Enrolled volunteers were excluded if found to be positive for HIV, syphilis or Hepatitis B and C. Laboratory assays were conducted under Good Clinical Laboratory Practices (GCLP). RESULTS AND CONCLUSIONS: Of the 2990 volunteers who were screened, 2387 (80%) were enrolled, and 2107 (71%) were included in the analysis (52% men, 48% women). Major reasons for screening out volunteers included abnormal findings on physical examination (228/603, 38%), significant medical history (76, 13%) and inability to complete the informed consent process (73, 13%). Once enrolled, principle reasons for exclusion from analysis included detection of Hepatitis B surface antigen (106/280, 38%) and antibodies against Hepatitis C (95, 34%). This is the first large scale, multi-site study conducted to the standards of GCLP to describe African laboratory reference intervals applicable to potential volunteers in clinical trials. Approximately one-third of all potential volunteers screened were not eligible for analysis; the majority were excluded for medical reasons.

Sanders EJ, Graham SM, Okuku HS, van der Elst EM, Muhaari A, Davies A, Peshu N, Price M, McClelland RS, Smith AD. 2007. HIV-1 infection in high risk men who have sex with men in Mombasa, Kenya. AIDS, 21 (18), pp. 2513-2520. | Show Abstract | Read more

BACKGROUND: The role of homosexuality and anal sex practices in the African HIV -1 epidemic is not well described. We aimed to assess the risk factors for prevalent HIV-1 infection among men who have sex with men (MSM) to guide HIV-1 prevention efforts. METHODS: Socio-behavioural characteristics, signs and symptoms of sexually transmitted diseases (STD), and serological evidence of HIV-1 were determined for 285 MSM at enrolment into a vaccine preparedness cohort study. We used multivariate logistic regression to assess risk factors for prevalent HIV-1 infection. RESULTS: HIV-1 prevalence was 43.0% [49/114, 95% confidence interval (CI), 34-52%] for men who reported sex with men exclusively (MSME), and 12.3% (21/171, 95% CI, 7-17%) for men who reported sex with both men and women (MSMW). Eighty-six (75%) MSME and 69 (40%) MSMW reported recent receptive anal sex. Among 174 MSM sexually active in the last week, 44% reported no use of condoms with casual partners. In the previous 3 months, 210 MSM (74%) reported payment for sex, and most clients (93%) were local residents. Prevalent HIV-1 infection was associated with recent receptive anal sex [odds ratio (OR), 6.1; 95% CI, 2.4-16], exclusive sex with men (OR, 6.3; 95% CI, 2.3-17), and increasing age (OR, 1.1 per year; 95% CI, 1.04-1.12). Only four MSM reported injecting drug use. CONCLUSIONS: The high prevalence of HIV-1 in Kenyan MSM is probably attributable to unprotected receptive anal sex. There is an urgent need for HIV-1 prevention programmes to deliver targeted risk-reduction interventions and STD services to MSM in Kenya.

Tsegaye A, Ran L, Wolday D, Petros B, Dorigo W, Piriou E, Messele T, Sanders E, Tilahun T, Eshetu D et al. 2007. HIV-1 Subtype C gag-specific T-cell responses in relation to human leukocyte antigens in a diverse population of HIV-infected Ethiopians. J Acquir Immune Defic Syndr, 45 (4), pp. 389-400. | Show Abstract | Read more

Knowledge of the most dominant T-cell epitopes in the context of the local human leukocyte antigen (HLA) background is a prerequisite for the development of an effective HIV vaccine. In 100 Ethiopian subjects, 16 different HLA-A, 23 HLA-B, and 12 HLA-C specificities were observed. Ninety-four percent of the population carried at least 1 of the 5 most common HLA-A and/or HLA-B specificities. HIV-specific T-cell responses were measured in 48 HIV-infected Ethiopian subjects representing a wide range of ethnicities in Ethiopia using the interferon (IFN)-gamma enzyme-linked immunospot (Elispot) assay and 49 clade C-specific synthetic Gag peptides. Fifty-eight percent of the HIV-positive study subjects showed T-cell responses directed to 1 or more HIV Gag peptides. Most Gag-specific responses were directed against the subset of peptides spanning Gag p24. The breadth of response ranged from 1 to 9 peptides, with most (78%) individuals showing detectable responses to <3 Gag peptides. The magnitude of HIV-specific T-cell responses was not associated with HIV viral load but correlated positively with CD4 T-cell counts. The most frequently targeted Gag peptides overlapped with those previously described for HIV-1 subtype C-infected southern Africans, and therefore can be used in a multiethnic vaccine.

Geibel S, van der Elst EM, King'ola N, Luchters S, Davies A, Getambu EM, Peshu N, Graham SM, McClelland RS, Sanders EJ. 2007. 'Are you on the market?': a capture-recapture enumeration of men who sell sex to men in and around Mombasa, Kenya. AIDS, 21 (10), pp. 1349-1354. | Show Abstract | Read more

BACKGROUND: Men who have sex with men (MSM) are highly vulnerable to HIV infection, but this population can be particularly difficult to reach in sub-Saharan Africa. We aimed to estimate the number of MSM who sell sex in and around Mombasa, Kenya, in order to plan HIV prevention research. METHODS: We identified 77 potential MSM contact locations, including public streets and parks, brothels, bars and nightclubs, in and around Mombasa and trained 37 MSM peer leader enumerators to extend a recruitment leaflet to MSM who were identified as 'on the market', that is, a man who admitted to selling sex to men. We captured men on two consecutive Saturdays, 1 week apart. A record was kept of when, where and by whom the invitation was extended and received, and of refusals. The total estimate of MSM who sell sex was derived from capture-recapture calculation. RESULTS: Capture 1 included 284 men (following removal of 15 duplicates); 89 men refused to participate. Capture 2 included 484 men (following removal of 35 duplicates); 75 men refused to participate. Of the 484 men in capture 2, 186 were recaptures from capture 1, resulting in a total estimate of 739 (95% confidence interval, 690-798) MSM who sell sex in the study area. CONCLUSIONS: We estimated that 739 MSM sell sex in and around Mombasa. Of these, 484 were contacted through trained peer enumerators in a single day. MSM who sell sex in and around Mombasa represent a sizeable population who urgently need to be targeted by HIV prevention strategies.

Karita E, Price M, Hunter E, Chomba E, Allen S, Fei L, Kamali A, Sanders EJ, Anzala O, Katende M et al. 2007. Investigating the utility of the HIV-1 BED capture enzyme immunoassay using cross-sectional and longitudinal seroconverter specimens from Africa. AIDS, 21 (4), pp. 403-408. | Show Abstract | Read more

BACKGROUND: The identification of populations at risk of HIV infection is a priority for trials of preventive technologies, including HIV vaccines. To quantify incidence traditionally requires laborious and expensive prospective studies. METHODS: The BED IgG-Capture enzyme immunoassay (EIA) was developed to estimate HIV-1 incidence using cross-sectional data by measuring increasing levels of HIV-specific IgG as a proportion of total IgG. To evaluate this assay, we tested 189 seroconversion samples taken at 3-monthly intervals from 15 Rwandan and 26 Zambian volunteers with known time of infection and cross-sectional specimens from 617 Kenyan and Ugandan volunteers with prevalent infection. RESULTS: The BED-EIA-estimated incidence in Uganda was unexpectedly high, at 6.1%/year [95% confidence interval (CI) 4.2-8.0] in Masaka and 6.0%/year (95% CI 4.3-7.7) in Kakira. Prospective incidence data in Masaka from the same population was 1.7%/year before and 1.4%/year after the study. Kenyan estimates were 3.5%/year in Kilifi (95% CI 2.1-4.9) and 3.4%/year in Nairobi (95% CI 1.5-5.3). From the Rwandan and Zambian data, the sensitivity of the assay was 81.2% and the specificity was 67.8%. After approximately one year, subjects misclassified as recently infected tended to have lower plasma viral loads compared with those not misclassified as recent (median copies/ml 14 773 versus 93 560; P = 0.02). Clinical presentation, sex and HIV subtype were not significantly associated with BED-EIA misclassification in seroconverter samples. CONCLUSION: These data suggest that this assay does not perform reliably in all populations. Further research is warranted before using this assay to estimate incidence from prevalent HIV samples.

Mekonnen Y, Sanders E, Messele T, Wolday D, Dorigo-Zestma W, Schaap A, Mekonnen W, Meless H, Mihret W, Fontanet A et al. 2005. Prevalence and incidence of, and risk factors for, HIV-1 infection among factory workers in Ethiopia, 1997-2001. J Health Popul Nutr, 23 (4), pp. 358-368. | Show Abstract

The study was conducted to determine the prevalence, incidence, and risk factors for HIV infection among factory workers at two sites in Ethiopia. During February 1997-December 2001, a structured questionnaire was used for obtaining information on sociodemographics, sexual behaviour, and reported sexually transmitted infections (STIs) from a cohort of 1679 individuals. Serum samples were screened for antibodies against HIV, Treponema pallidum haemaglutination (TPHA), and herpes simplex virus type 2 (HSV-2). The overall baseline prevalence of HIV was 9.4%-8.5% among males and 12.4% among females. For both the sexes, the factors independently associated with an increased risk of HIV infection were widowhood and having had antibodies against TPHA and HSV-2. The risk factors specific for males were being orthodox Christian, having had a higher lifetime number of sexual partners, and genital discharge in the past five years. The risk factors for females, included low income, one or more rape(s) over lifetime, and casual sex in the last year. The overall incidence of HIV infection was 0.4 per 100 person-years. The highest rate of incidence was observed among young women aged less than 30 years (1 per 100 person-years). The study confirmed that high-risk sexual behaviour and STIs play major roles in the spread of HIV infection in the Ethiopians of both the sexes, but the factors, such as rape and low economic status, make women more vulnerable than men.

Bruce MG, Sanders EJ, Leake JAD, Zaidel O, Bragg SL, Aye T, Shutt KA, Deseda CC, Rigau-Perez JG, Tappero JW et al. 2005. Leptospirosis among patients presenting with dengue-like illness in Puerto Rico. Acta Trop, 96 (1), pp. 36-46. | Show Abstract | Read more

Leptospirosis is difficult to distinguish from dengue fever without laboratory confirmation. Sporadic cases/clusters of leptospirosis occur in Puerto Rico, but surveillance is passive and laboratory confirmation is rare. We tested for leptospirosis using an IgM ELISA on sera testing negative for dengue virus IgM antibody and conducted a case-control study assessing risk factors for leptospirosis, comparing clinical/laboratory findings between leptospirosis (case-patients) and dengue patients (controls). Among 730 dengue-negative sera, 36 (5%) were positive for leptospirosis. We performed post mortem testing for leptospirosis on 12 available specimens from suspected dengue-related fatalities; 10 (83%) tested positive. Among these 10 fatal cases, pulmonary hemorrhage and renal failure were the most common causes of death. We enrolled 42 case-patients and 84 controls. Jaundice, elevated BUN, hyperbilirubinemia, anemia, and leukocytosis were associated with leptospirosis (p < .01 for all). Male sex, walking in puddles, rural habitation, and owning horses were independently associated with leptospirosis. Epidemiological, clinical, and laboratory criteria may help distinguish leptospirosis from dengue and identify patients who would benefit from early antibiotic treatment.

Abuye C, Tsegaye A, West CE, Versloot P, Sanders EJ, Wolday D, Hamann D, De Wit TFR, Fontanet AL. 2005. Determinants of CD4 counts among HIV-negative Ethiopians: role of body mass index, gender, cigarette smoking, khat (Catha Edulis) chewing, and possibly altitude? J Clin Immunol, 25 (2), pp. 127-133. | Show Abstract | Read more

To study the determinants of CD4% and CD4 counts among HIV-negative Ethiopians, and to identify factors susceptible to explain the low CD4 counts observed among Ethiopian subjects. Cohort studies among factory workers in Akaki and Wonji, Ethiopia. Clinical and laboratory examinations, including determination of HIV serological status and T-cell subsets, were performed during follow-up visits every six months. In addition, micronutrients (retinol, carotenoids, tocopherol, transferrin receptor, and selenium) plasma concentrations were determined in a subset of 38 HIV-positive and 121 HIV-negative participants. HIV-negative participants with at least one CD4 count measurement were 157 females in Akaki, 203 males in Akaki, and 712 males in Wonji. CD4 counts were independently and positively associated with body mass index (through an increase in lymphocyte counts), female gender (through an increase in CD4%), cigarette smoking (through an increase in CD4%), khat chewing (through an increase in both lymphocyte counts and CD4%), and Akaki study site (through a large increase in lymphocyte counts compensating a decrease in CD4%). Intestinal parasitic infections were not associated with CD4% or CD4 counts. Retinol, carotenoids, and alpha-tocopherol plasma concentrations decreased with HIV infection and advancing immunosuppression, but were not associated with CD4 counts among HIV-negative subjects. Low body mass index among Ethiopians may have contributed to their overall low CD4 counts. Other factors remain to be elucidated.

Eyob G, Guebrexabher H, Lemma E, Wolday D, Gebeyehu M, Abate G, Rigouts L, van Soolingen D, Fontanet A, Sanders E, Dorigo-Zetsma JW. 2004. Drug susceptibility of Mycobacterium tuberculosis in HIV-infected and -uninfected Ethiopians and its impact on outcome after 24 months of follow-up. Int J Tuberc Lung Dis, 8 (11), pp. 1388-1391. | Show Abstract

From a prospective cohort study on tuberculosis/human immunodeficiency virus (TB/HIV) interaction in Addis Ababa, Ethiopia, drug susceptibility results were available for 94 TB patients (46% HIV-infected). Resistance to one or more drug(s) was detected in 21 (22.3%) and multidrug resistance in five (5.3%) patients. Occurrence of resistance was not related to HIV status or outcome after 24 months of follow-up. However, among HIV-infected TB patients who died during follow-up, survival time in those with a resistant Mycobacterium tuberculosis strain was significantly shorter compared to those with a sensitive strain (6 vs. 13 months). Early detection of drug resistance and timely treatment change can therefore have a positive impact on survival in HIV-infected TB patients.

Kebede Y, Dorigo-Zetsma W, Mengistu Y, Mekonnen Y, Schaap A, Wolday D, Sanders EJ, Messele T, Coutinho RA, Dukers NHTM. 2004. Transmission of herpes simplex virus Type 2 among factory workers in Ethiopia. J Infect Dis, 190 (2), pp. 365-372. | Show Abstract | Read more

The herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) epidemics are believed to fuel each other, especially in sub-Saharan countries. In Ethiopia during 1997-2002, a retrospective study was conducted to examine risk factors for infection and transmission of HSV-2, in a cohort of 1612 factory workers. Prevalence of HSV-2 seropositivity at enrollment was 40.9%, and incidence of seroconversion was 1.8 seroconversions/100 person-years (PY), which decreased over time. Independent risk factors for seropositivity were having an HSV-2-seropositive partner, female sex, HIV antibodies, positive Treponema pallidum particle agglutination assay result, older age, low education level, and orthodox religion. These same factors were independent risk factors for HSV-2 seroconversion, with the exception of the latter 3. Most HSV-2-infected persons did not report symptoms. Among 41 monogamous HSV-2-serodiscordant heterosexual couples, incidence of HSV-2 seroconversion was 20.75 seroconversions/100 PY for women and 4.93 seroconversions/100 PY for men. The high burden of both HSV-2 and HIV infection in Ethiopia warrants stringent control measures.

Dorigo-Zetsma JW, Belewu D, Meless H, Sanders E, Coutinho RA, Schaap A, Wolday D. 2004. Performance of routine syphilis serology in the Ethiopian cohort on HIV/AIDS. Sex Transm Infect, 80 (2), pp. 96-99. | Show Abstract | Read more

OBJECTIVES: To assess the performance of routine syphilis screening during 5 year follow up of Ethiopian factory workers, participating in a cohort study on HIV/AIDS. METHODS: Syphilis serology test results of factory workers, who each donated at least six blood samples were evaluated. Screening in 1997-8 had been performed by the Treponema pallidum particle agglutination (TPPA) assay and in 1999-2001 by the rapid plasma reagin (RPR) test. TPPA had been followed by RPR or RPR by TPPA, in case of a positive screening result. Samples of study subjects showing inconsistent sequential TPPA and/or RPR results were retested independently by three laboratory technicians. RESULTS: A total of 540 cohort participants (8.3% HIV positive at enrollment) donated 4,376 blood samples (mean 8.3 per subject). From 93 of the 176 participants with at least one positive TPPA result during follow up, 152 samples were retested by RPR and/or TPPA. Based on the revised syphilis test results, the 540 cohort participants were classified as having no (70.5%), past (20.6%), prevalent (6.9%), or incident (2.0%) syphilis. The RPR screening test was difficult to interpret and yielded 8.2% biological false positive (BFP) RPR results, or 3.2% if weak positive results were excluded. There was no correlation between HIV infection and BFP RPR reactions. Sample mix-ups were detected in 1.2%. CONCLUSION: Evaluation of routine syphilis screening as performed in a long term cohort study on HIV/AIDS in Ethiopia showed difficulties encountered in syphilis screening programmes such as a high percentage of BFP RPR, inconsistencies in interpretation of the RPR test, and sample mix ups. The findings stress the need to develop a syphilis screening assay that is easy to perform and interpret and to implement quality assurance programmes.

Wolday D, Gebremariam Z, Mohammed Z, Dorigo-Zetsma W, Meles H, Messele T, Geyid A, Sanders E, Maayan S. 2004. The impact of syndromic treatment of sexually transmitted diseases on genital shedding of HIV-1. AIDS, 18 (5), pp. 781-785. | Show Abstract | Read more

OBJECTIVES: To examine the impact of sexually transmitted diseases (STD) syndromic treatment on genital shedding of HIV and the impact among women in whom STD treatment was not successful. DESIGN: Seventy-one HIV-infected women were included; 60 had symptomatic STD [72% with genital discharge syndrome (GDS) and 28% with genital ulcer syndrome (GUS)] and 11 controls did not have symptomatic STD. Cervical HIV load in 94% women was measured at baseline and after STD treatment. RESULTS: Cervical HIV load at entry was significantly higher in women with symptomatic STD than in controls [median, 3.15; interquartile range (IQR), 1.90-3.34 versus median, 1.90; IQR, 1.90-2.19 log10 RNA copies/swab, respectively; P = 0.024]. Women with STD were also more likely to have detectable cervical HIV RNA (68% versus 27%; P = 0.016). Cervical HIV load was significantly higher in women with GUS than in those with GDS (median 3.46; IQR, 2.84-4.18 versus median, 2.83; IQR, 1.90-3.31 log10 copies/swab; P = 0.019). There was no significant reduction in genital HIV shedding after syndromic treatment of GDS or GUS. However, significant decreases were limited to only those with clinical improvement (median, 2.91; IQR, 1.90-3.45 versus median, 2.25; IQR, 1.90-3.08 log10 RNA copies/swab, respectively; P = 0.006). GUS was significantly associated with treatment failure, independent of plasma HIV RNA load and CD4 T-cell count (odds ratio, 4.79; 95% confidence interval, 1.32-17.46). CONCLUSIONS: The fact that STD syndromic treatment impacts very little in reducing genital HIV shedding underscores the need for appropriate validation of STD syndromic diagnosis and management to control heterosexual transmission of HIV.

Araya T, Reniers G, Schaap A, Kebede D, Kumie A, Nagelkerke N, Coutinho R, Sanders E. 2004. Lay diagnosis of causes of death for monitoring AIDS mortality in Addis Ababa, Ethiopia. Trop Med Int Health, 9 (1), pp. 178-186. | Show Abstract | Read more

Lay diagnoses of death collected at burial sites were validated against two 'gold standards': the hospital discharge diagnosis of causes of death obtained by a surveillance of hospital deaths (including autopsy results) and the physician review of verbal autopsies (VAs) that were carried out for a sample of cemetery records. The diagnostic indicators of the lay diagnoses were then used to provide estimates of the share of AIDS-attribuTable mortality. The verbal autopsy results provide an independent estimate of the percentage of AIDS deaths. From a total of 21,274 burial records, 2546 hospital discharge diagnoses, 1480 outcomes of autopsies and 200 adult verbal autopsies were gathered over a period of 1 year starting from February 2001. Independent of the gold standard, lay diagnoses such as lung disease and cold have a specificity of about 90% and a combined sensitivity of about 55% in determining AIDS mortality. Without a significant loss in specificity, the sensitivity increases to 60-65% when diarrhoea, TB, herpes zoster and mental or nerve problem are included. We thus conclude that even in the presence of a reluctance to talk of HIV/AIDS, lay diagnosis of causes of death can be used for monitoring AIDS mortality. Lung disease and cold, in particular, have become well-known euphemisms for AIDS in the community. The share of AIDS deaths in the adult population (20-54) is estimated at 68%, without noticeable differences between men and women. Our results confirm the high impact of HIV/AIDS on mortality as was estimated by epidemiological projections for Addis Ababa.

Abebe Y, Schaap A, Mamo G, Negussie A, Darimo B, Wolday D, Sanders EJ. 2003. HIV prevalence in 72 000 urban and rural male army recruits, Ethiopia. AIDS, 17 (12), pp. 1835-1840. | Show Abstract | Read more

BACKGROUND: The recent estimate of around 2 million HIV-infected people in Ethiopia derives from data that are sparse, especially in the rural areas where the majority (> 85%) of the population lives. We assessed HIV prevalence in almost 72 000 army recruits who resided in urban and rural areas prior to recruitment. METHODS: Rapid HIV tests, HIVSPOT and Determine, were conducted on blood samples drawn at enrolment from almost 10 000 urban recruits, in 1999, and 62 000 rural recruits, in 2000. Socio-demographic data from recruits were available. RESULTS: In urban recruits, overall HIV prevalence was 7.2%, ranging from 4.3 to 10.5% depending on region. In rural recruits, overall HIV prevalence was 3.8%, but the majority were farmers (57%) and students (18%) with an HIV prevalence of 2.7% and 2.6%, respectively. (Higher) level of education in rural recruits was associated with HIV infection. Rural recruits of the Muslim religion were less likely to be HIV infected than recruits of the Orthodox Christian religion (odds ratio: 0.7; 95% confidence interval, 0.65-0.84). Urban and rural residents of Amhara region were at higher risk of HIV infection. CONCLUSION: Prevalence in both rural and urban army recruits is below previous estimates. Geographic distribution of HIV is uneven. The impact of religion, education, and region on HIV prevalence suggests avenues for targeting HIV prevention efforts in Ethiopia.

Sanders EJ, Messele T, Wolday D, Dorigo-Zetsma W, WoldeMichael T, Geyid A, Coutinho R. 2003. Development of research capability in Ethiopia: the Ethio-Netherlands AIDS research project (ENARP): 1994-2002, achievements, scientific findings and project goals. Ethiop Med J, 41 Suppl 1 pp. 11-23. | Show Abstract

In 1992, HIV/AIDS researchers in Amsterdam, the Netherlands, were invited to work in partnership with researchers in Ethiopia to build an HIV/AIDS research infrastructure in Addis Ababa. This project, which began in 1994, was envisioned to contribute meaningfully to fighting the HIV pandemic in the decades to come. Its immediate objective was to establish an HIV research laboratory to serve international partnerships pursuing HIV vaccine research in Ethiopia and to support national health authorities fighting the HIV epidemic in Ethiopia. The overall goal was to develop research capacity at the Ethiopian Health and Nutrition Research Institute (EHNRI) by improving facilities, training technical and academic personnel (at PhD, MSc, and MPH level), establishing cohort studies to study HIV infection progression, and helping the government to implement a national HIV surveillance program. In the period 1994-2002, the projected HIV/AIDS research laboratory was built and several existing sections of EHNRI were renovated and upgraded. An active HIV-research program was established. Staff grew to more than 60, including three Ethiopian and three expatriate research/managers. Two PhD. students have graduated in immunology and virology (University of Amsterdam, 2000), and five are currently in training. Several technical persons were trained and over 19 MSc/MPH-programs were supported at Addis Ababa University (AAU). The first Ethiopian PhD graduate became the national program manager for ENARP. Two ENARP cohort studies and several HIV-prevalence studies have helped to document the severity of the HIV epidemic in Ethiopia, assisting national authorities in formulation of national and regional policies to prevent HIV transmission. Initial funding for ENARP from the Netherlands government was projected for eight years, to end by 2003. It was expected that management responsibilities would then be transferred from expatriate to Ethiopian staff and all ENARP activities integrated into EHNRI.

Assefa T, Davey G, Dukers N, Wolday D, Worku A, Messele T, Tegbaru B, Dorigo W, Sanders EJ. 2003. Overall HIV-1 prevalence in pregnant women over-estimates HIV-1 in the predominantly rural population of Afar Region. Ethiop Med J, 41 Suppl 1 pp. 43-49. | Show Abstract

The appropriateness of sentinel sero-surveillance based upon ante-natal clinic (ANC) attendees to estimate HIV-1 prevalence in the general population has been questioned. In Ethiopia, where the population is heterogeneous and where economic and practical barriers to ANC attendance exist, problems of extrapolation may be exacerbated. We planned an unlinked anonymous sero-survey which included data on basic population characteristics to investigate whether sero-surveillance data from ANCs in Afar Region might be taken to represent the situation among the general population of the Region. 371 pregnant women attending Dubti Hospital and Assayta Health Centre were tested for HIV-1 (using a single ELISA test) and active syphilis (RPR test). Socio-demographic characteristics were collected for each woman. Of the women tested, 278 (75%) were 28 years of age or younger. Two hundred eighty (76%) were urban residents and 237 (64%) described themselves as being of Amhara ethnicity. Overall, 73 (19.7%) were HIV-1 positive, but prevalence was three times higher among the 237 women of Amhara ethnicity compared to the 112 of Afar ethnicity (24.9% vs 8.0%, p < 0.001), and almost three times higher for urban compared to rural residents (23.2% vs 8.8%, p < 0.001). Positive RPR results were strongly associated with HIV-1 infection (OR 3.37, 95% CI 1.47-7.71). According to the Demographic and Health Survey (DHS) 2000, only 4.5% of the population of Afar Region is of Amhara ethnicity, and 7.8% urban residents. We have demonstrated that basing ANC sero-surveillance in urban areas of Afar Region over-samples urban residents of Amhara ethnicity and yields a major over-estimation of overall HIV-1 prevalence for the Region. Reliable estimation of HIV-1 prevalence in Afar Region will require more flexible strategies that permit sampling of rural Afar residents.

Degefa A, Sanders EJ, Mekonnen Y, Messele T, Wolday D, Dorigo-Zetsma W, Mekonnen W, Schaap A, Dukers NH. 2003. Knowledge and attitudes towards antiretroviral therapy among factory workers participating in a cohort on HIV and AIDS, Addis Ababa, Ethiopia. Ethiop Med J, 41 Suppl 1 pp. 75-87. | Show Abstract

This study investigates barriers that may pose a threat to a successful implementation of an antiretroviral treatment (ART) program in Ethiopia. As prelude to the provision of ART among factory workers participating in a cohort study on HIV and AIDS in Ethiopia, we measured knowledge and attitudes towards several aspects of ART and provided an educational intervention. The proportion of participants having good knowledge on issues concerning adherence was found reasonably good (67.7%), concerning the benefit of ART was intermediate (37.7%) and concerning eligibility was very low (16.8%). Knowledge concerning eligibility improved somewhat after the provision of the educational intervention. Only one third of HIV infected persons discloses their HIV status to their partner. Several aspects that could impact adherence to ART will be discussed, such as ART knowledge, social support, willingness to take ART, and disclosure of serostatus, taking the cohort study site into account. Results indicate a tremendous need to educate cohort participants before and during introduction of ART. Efforts to increase knowledge of ART, and especially knowledge of eligibility criteria to start ART, seem warranted, as well as encouragement to identify social support and disclose HIV serostatus, as these factors directly impact the success of an ART program.

Tsegaye A, Rinke de Wit TF, Mekonnen Y, Beyene A, Aklilu M, Messele T, Abebe A, Coutinho R, Sanders E, Fontanet AL. 2003. Decline in prevalence of HIV-1 infection and syphilis among young women attending antenatal care clinics in Addis Ababa, Ethiopia: results from sentinel surveillance, 1995-2001. Ethiop Med J, 41 Suppl 1 pp. 31-34. | Show Abstract

From 1995 to 2001, five rounds of sentinel surveillance were carried out for young women attending antenatal care clinics at four health centers in Addis Ababa, the capital city of Ethiopia, to monitor trends in the prevalence of HIV infection and syphilis. Serum samples were tested for antibodies to HIV (enzyme-linked immunosorbent assay and Western blotting) and antibodies to Treponema pallidum (T. pallidum hemagglutination assay and rapid plasma reagin test). Prevalence ratios for an increase in one calendar year were estimated using log-binomial models. Between 1995 and 2001, the prevalence of HIV infection among young women (age range, 15-24 years) attending antenatal care clinics in inner city health centers declined from 24.2% to 15.1% (prevalence ratio for an increase in one calendar year, 0.91; 95% confidence interval, 0.87-0.95). No change was observed for older age groups or in outer city health centers. The decline in the prevalence of active syphilis (T. pallidum hemagglutination assay and rapid plasma reagin testing positive for antibodies to T. pallidum) was more pronounced among and also restricted to the young age groups (age range, 15-24 years) in the inner city (from 7.6% in 1995 to 1.3% in 2001; prevalence ratio, 0.69; 95% confidence interval, 0.59-0.80). The declining trends in the prevalence of HIV infection and syphilis among young women attending antenatal care clinics in the inner city are encouraging, but these findings require confirmation in future years and for other population groups.

Sanders E. 2003. Partnership for HIV vaccine research in Africa. Ethiop Med J, 41 Suppl 1 pp. 5-7.

Sanders EJ, Araya T, Kebede D, Schaap AJ, Nagelkerke ND, Coutinho RA. 2003. Mortality impact of AIDS in Addis Ababa, Ethiopia. AIDS, 17 (8), pp. 1209-1216. | Show Abstract | Read more

OBJECTIVE: To measure the impact of HIV on mortality in Addis Ababa, Ethiopia. DESIGN: A retrospective review of burials at three cemeteries, 1987-2001 and a prospective surveillance of burials at all (n = 70) cemeteries, February-May, 2001. METHODS: The age, sex, and date of burial were recorded; in the absence of denominators, we compared the ratio of deaths of persons 25-49 versus 5-14 years of age per calendar year, using logistic regression, adjusting for sex and site. The age- and sex- specific mortality were calculated and compared with pre-HIV mortality in 1984. RESULTS: Of 17,519 deaths, retrospectively reviewed, complete data were available for 6342 (47%) females and 7269 (53%) males. During 1987-2001, the '25-49' versus '5-14' group all-cause mortality ratio increased by 8.5% per calendar year (P < 0.05). A total of 5101 deaths were recorded in the prospective surveillance. Crude mortality rates were 9.5/1000 per year (men) and 7.1/1000 per year (women). In comparison with 1984, 5.0-times as many men and 5.3-times as many women died in the age group 35-39 years. Attributing the increase in mortality in ages 15-60 to HIV in the period 1984-2001, Ethiopian men and women have a probability of 18.8 and 17.8%, respectively, of dying of HIV before age 60. CONCLUSION: Burials increased significantly among the '25-49', versus the '5-14' group, during the period 1987-2001. This trend, and a five-times higher mortality in 2001 than in 1984 in those aged 35-39 years demonstrate a severe impact of HIV on mortality. Continuing surveillance of burials is recommended.

Kebede A, Verweij J, Dorigo-Zetsma W, Sanders E, Messele T, van Lieshout L, Petros B, Polderman T. 2003. Overdiagnosis of amoebiasis in the absence of Entamoeba histolytica among patients presenting with diarrhoea in Wonji and Akaki, Ethiopia. Trans R Soc Trop Med Hyg, 97 (3), pp. 305-307. | Show Abstract | Read more

To confirm the high reported incidence of intestinal amoebiasis among study participants at 2 cohort sites in Ethiopia where an HIV/AIDS study is taking place, stool samples of 232 patients with complaints of diarrhoea were examined for the presence of Entamoeba histolytica and E. dispar DNA between April and December 2001. By microscopy, 91 (39%) of the study participants were reported to harbour Entamoeba trophozoites and/or four-nucleated cysts. Using specific E. histolytica and E. dispar DNA amplification and detection, none of the study participants were found to be infected with E. histolytica and only 21 (9%) with E. dispar. The consequences of the overdiagnosis of E. histolytica are briefly discussed.

Mekonnen Y, Dukers NH, Sanders E, Dorigo W, Wolday D, Schaap A, Geskus RB, Coutinho RA, Fontanet A. 2003. Simple markers for initiating antiretroviral therapy among HIV-infected Ethiopians. AIDS, 17 (6), pp. 815-819. | Show Abstract | Read more

BACKGROUND: We explored the relevance of simple markers (clinical or laboratory markers not requiring sophisticated laboratories) in the decision of initiation of therapy in resource-poor settings. METHODS: Among HIV-infected Ethiopian cohort participants, simple markers predicting short-term death were examined using time-dependent Cox proportional hazards models. Timing of hypothetical treatment was compared between guidelines using the simple markers (based on presence of at least one marker), guidelines recommended by the United States Department of Health and Human Services (based on CD4 cell count and viral load), and guidelines for resource-limited settings recommended by the World Health Organization (WHO). RESULTS: From February 1997 to August 2001, 35 deaths were recorded among 155 HIV-positive participants. Simple independent predictors of death were low body mass index, HIV-related conditions, anaemia, and lymphocyte count < 1500 x 106/l. In such time as was covered by our study, 135 (87%) of 155 cohort participants would have had the same management under both the simple markers and the DHHS guidelines, i.e., would have been treated (n = 114, 74%) or not treated (n = 21, 14%). Of the 114 participants hypothetically treated under either set of guidelines, 91 (80%) would have started treatment at the same time. Application of the WHO guidelines for resource-limited settings (without CD4 cell counts) would have resulted in 11 participants dying without ever meeting a treatment indication during regular follow-up visits. CONCLUSION: Simple markers for the initiation of highly active antiretroviral therapy were identified among HIV-infected Ethiopian patients. The validity of these markers for monitoring patients' improvement following therapy remains to be evaluated.

Kassu A, Tsegaye A, Wolday D, Petros B, Aklilu M, Sanders EJ, Fontanet AL, Van Baarle D, Hamann D, De Wit TFR. 2003. Role of incidental and/or cured intestinal parasitic infections on profile of CD4+ and CD8+ T cell subsets and activation status in HIV-1 infected and uninfected adult Ethiopians. Clin Exp Immunol, 132 (1), pp. 113-119. | Show Abstract | Read more

Intestinal parasitic infections have been suggested to cause persistent immune activation leading to an unbalanced immune state. Such a state has been proposed to be a major factor in the pathogenesis of AIDS in an African context. The present study investigated the effect of incidental parasitic infection and treatment on the profile of T cell differentiation and activation markers on CD4+ and CD8+ T cells from HIV-1 infected and uninfected adult Ethiopians. Cryopreserved PBMCs from 64 subjects (41 HIV-negative and 23 HIV-positive) with follow-up visits at 6-monthly intervals were used to compare the effect of incidental intestinal parasites and their treatment upon T cell subset profiles and activation status. The samples were stained with antibodies to various T cell differentiation and activation markers allowing naive, memory, effector, memory/effector, activated and resting CD4+ and CD8+ T cell subsets to be quantified by triple-colour FACScan. Incidental intestinal parasitic infections resulted in a significant increase in memory CD4+ T cell numbers both in HIV-negative and HIV-positive subjects (P < 0.05). There was also a significant increase in the percentage of CD8+ HLA-DR+ T cells (P < 0.05) in HIV-positive subjects co-infected with parasites. In HIV-negative subjects, a significant decline in activated cells and a significant increase in resting CD8+ T cells (P < 0.05) was observed after treatment for parasites. These data suggest that intestinal parasitic infections could result in the alteration of T cell subset counts and also in the up-regulation of T cell activation markers in peripheral blood. Treatment of parasitic infections showed a tendency to reduce the activation suggesting that, together with other community based intervention strategies, such treatment could be used to down-regulate immune activation and hence protect the host from being easily attacked by HIV.

Mekonnen Y, Sanders E, Aklilu M, Tsegaye A, Rinke de Wit TF, Schaap A, Wolday D, Geskus R, Coutinho RA, Fontanet AL. 2003. Evidence of changes in sexual behaviours among male factory workers in Ethiopia. AIDS, 17 (2), pp. 223-231. | Show Abstract | Read more

OBJECTIVE: To assess changes in sexual behaviours among male factory workers in Ethiopia. DESIGN: Open cohort studies in two factories near Addis Ababa. DATA AND METHODS: At intake and biannual follow-up visits, data were collected on sexual behaviours including casual sex, sex with commercial sex workers (CSW), condom use, and history of sexually transmitted diseases (STDs) as indicated by genital discharge and genital ulcer. Health education, HIV testing, and counselling were offered to all participants. RESULTS: Between February 1997 and December 1999, 1124 males were enrolled in the two cohort studies. At intake, the prevalence of casual sex in the past year, sex with CSWs, condom use with the last casual partner, history of genital discharge in the past 5 years, and history of genital ulcer in the past 5 years were 9.7, 43.4, 38.8 (Akaki site only), 10.6 and 2.1%, respectively. At the Wonji site, the intake prevalence of casual sex, sex with CSW, and history of genital discharge decreased significantly by calendar year between 1997 and 1999. At both sites combined, between the first and the fourth follow-up visits, there was a decline in the proportion of males reporting recent casual sex (from 17.5 to 3.5%, < 0.001), sex with CSWs (from 11.2 to 0.75%, < 0.001), and genital discharge (from 2.1 to 0.6%, = 0.004). CONCLUSION: There was a decline over time in risky sexual behaviours reported by cohort participants. Part of this decline occurred independently of cohort interventions.

Rinke de Wit TF, Tsegaye A, Wolday D, Hailu B, Aklilu M, Sanders E, Hagos M, Kliphuis A, Pollakis G, Krol A et al. 2002. Primary HIV-1 subtype C infection in Ethiopia. J Acquir Immune Defic Syndr, 30 (5), pp. 463-470. | Show Abstract | Read more

Between 1997 and 2001, 1624 Ethiopian factory workers were enrolled in prospective HIV-1 cohorts in Ethiopia, at Akaki and Wonji towns. HIV-1 seroprevalence at intake was 11.8% (Akaki) and 7.1% (Wonji). HIV-1 incidence was .75 per 100 person-years (Akaki) and .35 per 100 person-years (Wonji). During follow up, CD4 T-cell counts remained significantly lower and CD8 T-cell counts significantly higher in Ethiopian seroconverters compared with Dutch seroconverters. Viral loads were lower in Ethiopian seroconverters versus Dutch seroconverters in the first months after seroconversion, subsequently increasing to similar levels. All 20 Ethiopian seroconverters were infected with HIV-1 subtype C (15 with sub-cluster C' and 5 with sub-cluster C). Viral loads were higher in sub-cluster C'-infected Ethiopian seroconverters. One subject demonstrated a window period of at least 204 days, combined with a high preseroconversion viral load and no decline of CD4 T cells over a follow-up period of at least 3 years.

Meless H, Tegbaru B, Messele T, Tilahun T, Dorigo-Zetsma W, Sanders E, Wolday D. 2002. Evaluation of rapid assays for screening and confirming HIV-1 infection in Ethiopia. Ethiop Med J, 40 Suppl 1 pp. 27-36. | Show Abstract

To evaluate a simple and rapid testing strategy to diagnose HIV infection in Ethiopia, we subjected a panel of 688 sera with known HIV serologic status (confirmed by ELISA/WB or double ELISA) to 3 rapid assays: Determine HIV-1/2, Capillus HIV-1/2 and Serocard HIV. Samples were obtained from participants in a cohort study on HIV-infection (72%), from tuberculosis patients (18%) and from participants in surveillance studies among police recruits and commercial sex workers (10%). The panel consisted of 249 HIV-1 positive samples, of which 68 were HIV-1 subtype C and 1 HIV-1 subtype A, and 439 HIV-1 negative samples. Determine and Capillus were 100% sensitive and 99.8% specific, Serocard was 100% sensitive and specific. On retrospective evaluation, both parallel (samples tested simultaneously by two rapid assays) and serial (samples tested by two consecutive rapid assays) testing algorithms were 100% sensitive and specific when compared to ELISA/WB or double ELISA testing strategy. In conclusion rapid assays have high sensitivity and specificity. HIV serodiagnosis based on rapid assays may therefore be a valuable alternative in voluntary counselling and testing centres and in facilities where sophisticated laboratories are not available.

Zewde A, Bahiru S, Sanders E, Tilahun T, Beyene A, Alebachew M, Schaap A, Wolday D, Rinke de Wit TF. 2002. HIV-1 seroprevalence and subtypes in police recruits from Afar regional state, Ethiopia. Ethiop Med J, 40 Suppl 1 pp. 1-10. | Show Abstract

Surveillance for HIV-1 prevalence and subtypes in Afar Region, Ethiopia was performed among police recruits in the year 2000, by unlinked anonymous testing. Of 408 samples tested, 26 (6.4%) appeared positive for HIV-1 antibodies. There was a trend for higher HIV-1 seroprevalence in women (9.5%, 9/95) than men (5.4%, 17/313), which was significant in one of the 5 administrative areas: Zone 4 (p = 0.01). Around the principal transportation route connecting Addis Ababa to the harbor of Djibouti there was a significantly (p = 0.03) higher HIV-1 seroprevalence of 12.7% (14/110) than elsewhere in Afar Region. In addition, 13 (34%) of the 29 administrative sub-areas (woredas) of Afar Region delivered HIV-1 positive police recruits. Prevalence of syphilis antibodies was 7.4% (30/408), increasing by age, correlating with HIV-1 positive serology (p = 0.001) and with 23.3% (7/30) active cases. Of 22 specimens sequenced, 12 had gp120 V3 regions from Ethiopian subtype C, 9 subtype C' and 1 subtype A. In conclusion, even in very remote areas in Ethiopia, such as Afar Region, the HIV-1 epidemic is established, being primarily of subtype C. Regular HIV-1 surveillances will be necessary to guide action to prevent further spread in this vulnerable area.

Mihret W, Rinke de Wit TF, Petros B, Mekonnen Y, Tsegaye A, Wolday D, Beyene A, Aklilu M, Sanders E, Fontanet AL. 2002. Herpes simplex virus type 2 seropositivity among urban adults in Africa: results from two cross-sectional surveys in Addis Ababa, Ethiopia. Sex Transm Dis, 29 (3), pp. 175-181. | Show Abstract | Read more

BACKGROUND: Although several surveys investigating the epidemiology of herpes simplex virus type 2 (HSV-2) infection using type-specific immunologic assays have been carried out in Africa, none has examined the risk factors for HSV-2 infection in a representative sample from an urban adult population. GOALS: To estimate the prevalence of HSV-2 infection in the adult population of Addis Ababa, Ethiopia, and to identify risk factors for HSV-2 infection. STUDY DESIGN: Two cross-sectional surveys, one community-based (June to September 1996, n = 506) and one factory-based (February to November 1997, n = 657), were conducted. Samples were tested for HSV-2 immunoglobulin G antibodies using type-specific enzyme-linked immunoassays (ELISA). RESULTS: In the community-based survey, HSV-2 prevalence increased with age until 25 years, then leveled off at 50% in both genders. The same independent predictors of HSV-2 infection were identified in both genders: older age, higher lifetime number of sexual partners, positive HIV serology, and positive Treponema pallidum hemagglutination serology. CONCLUSIONS: This study confirmed the high prevalence of HSV-2 infection among adults in an African urban population and its association with HIV infection. Prevention of HSV-2 and other sexually transmitted infections through partner reduction and condom use should be encouraged.

Meles H, Wolday D, Fontanet A, Tsegaye A, Tilahun T, Aklilu M, Sanders E, De Wit TFR. 2002. Indeterminate human immunodeficiency virus Western blot profiles in ethiopians with discordant screening-assay results. Clin Diagn Lab Immunol, 9 (1), pp. 160-163. | Show Abstract | Read more

The Western blot (WB) assay is the most widely accepted confirmatory assay for the detection of antibodies to human immunodeficiency virus type 1 (HIV-1). However, indeterminate WB reactivity to HIV-1 proteins may occur in individuals who do not appear to be infected with HIV. The profiles of WB reactivity among Ethiopians are hardly known. Here, we describe the profiles of indeterminate WB reactivity in Ethiopians with discordant screening assays. Between 1996 and 2000, a total of 12,124 specimens were tested for HIV-1 antibodies. Overall, 1,437 (11.9%) were positive for HIV-1 antibody. Ninety-one ( approximately 0.8%) gave equivocal results because of discordant results among the various screening assays and indeterminate WB profiles by the American Red Cross (ARC) criteria. Most (30.4%) of these indeterminate WB results were due to p24 reactivity. However, 12 samples (13.2%) displayed reactivity to p24 and gp41 or to p24 and gp120/160 proteins (positive by Centers for Disease Control and Prevention [CDC] criteria). Only two samples (2.2%) were reactive to both env glycoproteins gp41 and gp120/160 (positive by the World Health Organization [WHO] criteria). Of 31 WB assays initially indeterminate by the ARC criteria and with follow-up samples, 29 (93.5%) became negative when retested subsequently while 2 (6.5%) remained indeterminate for more than a year and were thus considered negative. Using CDC and WHO criteria, 6 (19.4%) and 2 (6.5%), respectively, of these WB assays would have been considered falsely positive. In addition, 17 indeterminate samples were negative when assessed by a nucleic acid-based amplification assay for HIV-1 viremia. In general, there was 97.8% concordance between the ARC and WHO criteria and 85.7% concordance between the ARC and CDC criteria for an indeterminate WB result. The ARC criteria best met the specified objectives for diagnosis in our setting.

Lulseged S, Sanders E. 2001. Ethiopian Medical Journal: looking into the future. Ethiop Med J, 39 (3), pp. 171-172.

Sanders EJ, de Wit TF, Fontanet AL, Goudsmit J, Miedema F, Coutinho RA. 2001. [Ethiopia-Netherlands AIDS research project]. Ned Tijdschr Geneeskd, 145 (26), pp. 1261-1265. | Show Abstract

The 'Ethiopia-Netherlands AIDS Research Project' (ENARP), started in 1994, is a long-term collaboration between AIDS researchers in Amsterdam and the Ethiopian Health and Nutrition Research Institute in Addis Ababa. The ENARP's primary objectives include conducting studies on HIV and AIDS in Ethiopia, especially by means of some large-scale prospective cohort studies, training Ethiopian scientists in PhD programmes in epidemiology, immunology and virology and establishing a reference laboratory for HIV and AIDS in Ethiopia and neighbouring countries. External funding for ENARP amounts to 32 million Dutch guilders for two periods of four years and is being provided by the Dutch Government. ENARP is the largest third world biomedical project supported by the Dutch Government. In 2000 two Ethiopian students obtained their doctorates from the University of Amsterdam. Five new PhD students commenced their training in 1999. ENARP hopes to set up HIV-1 vaccine phase I and phase II trials in the near future.

de Wit TF, Sanders EJ, Fontanet AL, Goudsmit J, Miedema F, Coutinho RA. 2001. [Results from the 'Ethiopia-Netherlands AIDS Research Project'; 1995-2000]. Ned Tijdschr Geneeskd, 145 (26), pp. 1236-1240. | Show Abstract

Since 1995 the 'Ethiopia-Netherlands aids research project' (ENARP) has been up and running in Addis Ababa, Ethiopia. Several surveys point towards an HIV seroprevalence of approximately 15% amongst adult Ethiopians in the capital city. Prospective cohort studies initiated since early 1997 indicate that healthy, HIV negative Ethiopians have lower CD4+ T-cell counts compared to the Dutch population and in addition they have chronically activated immune systems, possibly as a result of the highly prevalent intestinal parasitic infections as well as other infections. HIV positive Ethiopians are mainly infected with HIV-1 subtype C, which can be subdivided in 2 subtypes, both of which entered Ethiopia in the early 1980's. There are considerable differences between Ethiopians and Dutch in terms of biomedical parameters relevant for HIV infection progression; these justify further efforts in future scientific research. The emphasis for this should be on robust and applicable laboratory methods, research in the field of HIV vaccine trials and information transfer to the various partners combating HIV infection/aids in Ethiopia.

Kebede D, Aklilu M, Sanders E. 2000. The HIV epidemic and the state of its surveillance in Ethiopia. Ethiop Med J, 38 (4), pp. 283-302. | Show Abstract

A review of the information on the HIV epidemic in Ethiopia is important to guide policy and action. Published and unpublished reports and surveillance data from records of governmental and non-governmental institutions were examined to assess the extent of the epidemic. It appears that the HIV/AIDS epidemic has affected a large segment of the urban population. Surveillance data from pregnant women attending antenatal clinics indicate a decreasing trend in the prevalence of HIV in Addis Ababa. Similarly, data from blood donors from the majority of transfusion centres in the country indicate a decrease in prevalence. However, further studies will be required to establish the validity of these findings. Currently available data are not adequate to accurately measure the level of infection in rural areas where 85% of the population live. Outside of Addis Ababa, in places where ANC-based sentinel surveillance are operational, the systems are not fully supported by quality control. Thus, there are concerns regarding the validity of reported results. The impact of HIV/AIDS epidemic in Ethiopia needs to be further quantified both in its burden of diseases and its impact on the urban and rural economy and society. It is, therefore, important that effort and adequate resources are put into strengthening surveillance systems.

Sanders E. 2000. Development of research capability in Ethiopia: the Ethio-Netherlands HIV/AIDS Research Project (ENARP), 1994-2002. Northeast Afr Stud, 7 (2), pp. 101-117. | Show Abstract

History of the Ethio-Netherlands HIV/AIDS Research Project (ENARP), 1994-2002 and Ethiopia's HIV/AIDS Prevention and Control Council.

Kiwanuka N, Sanders EJ, Rwaguma EB, Kawamata J, Ssengooba FP, Najjemba R, Were WA, Lamunu M, Bagambisa G, Burkot TR et al. 1999. O'nyong-nyong fever in south-central Uganda, 1996-1997: clinical features and validation of a clinical case definition for surveillance purposes. Clin Infect Dis, 29 (5), pp. 1243-1250. | Show Abstract | Read more

O'nyong-nyong (ONN) fever, caused by infection with a mosquito-borne central African alphavirus, is an acute, nonfatal illness characterized by polyarthralgia. During 1996-1997, south-central Uganda experienced the second ONN fever epidemic ever recognized. Among 391 persons interviewed and sampled, 40 cases of confirmed and 21 of presumptive, well-characterized acute, recent, or previous ONN fever were identified through active case-finding efforts or during a household serosurvey and by the application of clinical and laboratory criteria. Among confirmed cases, the knees and ankles were the joints most commonly affected. The median duration of arthralgia was 6 days (range, 2-21 days) and of immobilization was 4 days (range, 1-14 days). In the majority, generalized skin rash was reported, and nearly half had lymphadenopathy, mainly of the cervical region. Viremia was documented in 16 cases, primarily during the first 3 days of illness, and in some of these, body temperature was normal. During this epidemic, the combination of fever, arthralgia, and lymphadenopathy had a specificity of 83% and a sensitivity of 61% in the identification of cases of ONN fever and thus could be useful for surveillance purposes.

Sanders EJ, Rwaguma EB, Kawamata J, Kiwanuka N, Lutwama JJ, Ssengooba FP, Lamunu M, Najjemba R, Were WA, Bagambisa G, Campbell GL. 1999. O'nyong-nyong fever in south-central Uganda, 1996-1997: description of the epidemic and results of a household-based seroprevalence survey. J Infect Dis, 180 (5), pp. 1436-1443. | Show Abstract | Read more

O'nyong-nyong (ONN) fever, an acute, nonfatal illness characterized by polyarthralgia, is caused by infection with a mosquito-borne central African alphavirus. During 1996-1997, south-central Uganda experienced the second ONN fever epidemic ever recognized. During January and early February 1997, active case-finding and a household cluster serosurvey were conducted in two affected and two comparison areas. A confirmed case was defined as an acute febrile illness with polyarthralgia occurring within the previous 9 months plus serologic confirmation or isolation of ONN virus from blood. In affected (n=129) and comparison (n=115) areas, the estimated infection rates were 45% and 3%, respectively, and the estimated attack rates were 29% and 0%, respectively, for an apparent:inapparent infection ratio of nearly 2 in affected areas. In villages sampled near Lake Kijanebalola, Rakai District, the estimated infection and attack rates were 68% and 41%, respectively, and 55% of sampled households had >/=1 case of ONN fever. In conclusion, this epidemic was focused near lakes and swamps, where it was associated with high infection and attack rates.

Sanders EJ, Rigau-Pérez JG, Smits HL, Deseda CC, Vorndam VA, Aye T, Spiegel RA, Weyant RS, Bragg SL. 1999. Increase of leptospirosis in dengue-negative patients after a hurricane in Puerto Rico in 1996 [correction of 1966]. Am J Trop Med Hyg, 61 (3), pp. 399-404. | Show Abstract | Read more

Leptospirosis has rarely been reported in Puerto Rico, although in the period from 1948 to 1952, 208 cases of leptospirosis and an island-wide seroprevalence of antibody to Leptospira of 14% were documented. In Puerto Rico in October 1996, following rainfall and a period of flooding generated by Hurricane Hortense, serum specimens of 4 patients with suspected dengue fever that were negative for dengue tested positive for Leptospira-specific IgM antibodies in a dipstick assay. Subsequently, we used an island-wide dengue laboratory-based surveillance system to determine the increase in leptospirosis after hurricane-generated floods. All anti-dengue IgM-negative patients (n = 142) with disease onset from August 8 to October 6, 1996 from prehurricane and posthurricane groups were investigated for leptospirosis. Laboratory-confirmed leptospirosis cases were defined as microscopic agglutination test titers > or = 1 :400 to 1 or more serovars, or positive immunohistochemistry in autopsy tissues. Four (6%) of 72 prehurricane and 17 (24%) of 70 posthurricane patients had laboratory-confirmed cases of leptospirosis (relative risk [RR] = 4.4, 95% confidence interval [CI] = 1.6-12.4). The mean age of case-patients was 34 years (range = 13-64). Eighteen (86%) of 21 confirmed case-patients were males, including one patient who died (31 years old). Patients were located in 18 (38%) of 48 municipalities that submitted serum samples. Clinical features significantly associated with leptospirosis were eye pain (RR = 1.5, 95% CI = 1.3-1.9), joint pain (RR = 1.4, 95% CI = 1.1-1.6), diarrhea (RR = 1.7, 95% CI = 1.2-2.5), and jaundice (RR = 3.3, 95% CI = 1.5-7.2). This study demonstrates the utility of a dengue laboratory-based surveillance system for the detection of an increase of leptospirosis, which most likely would have gone unrecognized. Leptospirosis is treatable with antibacterial agents; knowledge of this diagnosis may significantly reduce morbidity and mortality.

Reiter P, Cordellier R, Ouma JO, Cropp CB, Savage HM, Sanders EJ, Marfin AA, Tukei PM, Agata NN, Gitau LG et al. 1998. First recorded outbreak of yellow fever in Kenya, 1992-1993. II. Entomologic investigations. Am J Trop Med Hyg, 59 (4), pp. 650-656. | Show Abstract | Read more

The first recorded outbreak of yellow fever in Kenya occurred from mid-1992 through March 1993 in the south Kerio Valley, Rift Valley Province. We conducted entomologic studies in February-March 1993 to identify the likely vectors and determine the potential for transmission in the surrounding rural and urban areas. Mosquitoes were collected by landing capture and processed for virus isolation. Container surveys were conducted around human habitation. Transmission was mainly in woodland of varying density, at altitudes of 1,300-1,800 m. The abundance of Aedes africanus in this biotope, and two isolations of virus from pools of this species, suggest that it was the principal vector in the main period of the outbreak. A third isolate was made from a pool of Ae. keniensis, a little-known species that was collected in the same biotope. Other known yellow fever vectors that were collected in the arid parts of the valley may have been involved at an earlier stage of the epidemic. Vervet monkeys and baboons were present in the outbreak area. Peridomestic mosquito species were absent but abundant at urban sites outside the outbreak area. The entomologic and epidemiologic evidence indicate that this was a sylvatic outbreak in which human cases were directly linked to the epizootic and were independent of other human cases. The region of the Kerio Valley is probably subject to recurrent wandering epizootics of yellow fever, although previous episodes of scattered human infection have gone unrecorded. The risk that the disease could emerge as an urban problem in Kenya should not be ignored.

Sanders EJ, Marfin AA, Tukei PM, Kuria G, Ademba G, Agata NN, Ouma JO, Cropp CB, Karabatsos N, Reiter P et al. 1998. First recorded outbreak of yellow fever in Kenya, 1992-1993. I. Epidemiologic investigations. Am J Trop Med Hyg, 59 (4), pp. 644-649. | Show Abstract | Read more

Outbreaks of yellow fever (YF) have never been recorded in Kenya. However, in September 1992, cases of hemorrhagic fever (HF) were reported in the Kerio Valley to the Kenya Ministry of Health. Early in 1993, the disease was confirmed as YF and a mass vaccination campaign was initiated. Cases of suspected YF were identified through medical record review and hospital-based disease surveillance by using a clinical case definition. Case-patients were confirmed serologically and virologically. We documented 55 persons with HF from three districts of the Rift Valley Province in the period of September 10, 1992 through March 11, 1993 (attack rate = 27.4/100,000 population). Twenty-six (47%) of the 55 persons had serologic evidence of recent YF infection, and three of these persons were also confirmed by YF virus isolation. No serum was available from the other 29 HF cases. In addition, YF virus was isolated from a person from the epidemic area who had a nonspecific febrile illness but did not meet the case definition. Five patients with confirmed cases of YF died, a case-fatality rate of 19%. Women with confirmed cases of YF were 10.9 times more likely to die than men (P = 0.010, by Fisher's exact test). Of the 26 patients with serologic or virologic evidence of YF, and for whom definite age was known, 21 (81%) were between 10 and 39 years of age, and 19 (73%) were males. All patients with confirmed YF infection lived in rural areas. There was only one instance of multiple cases within a single family, and this was associated with bush-clearing activity. This was the first documented outbreak of YF in Kenya, a classic example of a sylvatic transmission cycle. Surveillance in rural and urban areas outside the vaccination area should be intensified.

Rigau-Pérez JG, Clark GG, Gubler DJ, Reiter P, Sanders EJ, Vorndam AV. 1998. Dengue and dengue haemorrhagic fever. Lancet, 352 (9132), pp. 971-977. | Show Abstract | Read more

The incidence and geographical distribution of dengue have greatly increased in recent years. Dengue is an acute mosquito-transmitted viral disease characterised by fever, headache, muscle and joint pains, rash, nausea, and vomiting. Some infections result in dengue haemorrhagic fever (DHF), a syndrome that in its most severe form can threaten the patient's life, primarily through increased vascular permeability and shock. The case fatality rate in patients with dengue shock syndrome can be as high as 44%. For decades, two distinct hypotheses to explain the mechanism of DHF have been debated-secondary infection or viral virulence. However, a combination of both now seems to be the plausible explanation. The geographical expansion of DHF presents the need for well-documented clinical, epidemiological, and virological descriptions of the syndrome in the Americas. Biological and social research are essential to develop effective mosquito control, medications to reduce capillary leakage, and a safe tetravalent vaccine.

Dunster LM, Sanders EJ, Borus P, Tukei PM. 1997. Yellow fever in Kenya: the need for a country-wide surveillance programme. World Health Stat Q, 50 (3-4), pp. 178-184. | Show Abstract

Since the emergence of yellow fever (YF) as a public health threat in Kenya in 1992-1993, low level transmission of the virus to humans has continued to occur. A programme of YF surveillance has been instrumental in the monitoring of YF activity and has clearly demonstrated an expansion of the zone of virus activity into regions that were not affected in the 1992-1993 epidemic. This is of major concern for the approximately 29 million Kenyans who are unvaccinated and therefore at risk of infection. A revision of the surveillance programme is underway to create a more efficient system of recognition of suspect YF cases, laboratory diagnosis and reporting to the appropriate authorities for action. In addition, a research programme to study YF ecology in Kenya will benefit the surveillance programme, enabling it to target potential 'hotspots' of YF activity. As it may not be possible, for financial reasons, to incorporate YF vaccination into the Kenya Expanded Programme of immunization in the immediate future, the need for continued surveillance to monitor the emergence of YF in Kenya is vital.

Sanders EJ, Borus P, Ademba G, Kuria G, Tukei PM, LeDuc JW. 1996. Sentinel surveillance for yellow fever in Kenya, 1993 to 1995. Emerg Infect Dis, 2 (3), pp. 236-238. | Read more

Sanders EJ, Tukei PM. 1996. Yellow fever: an emerging threat for Kenya and other east African countries. East Afr Med J, 73 (1), pp. 10-12. | Show Abstract

Yellow fever (YF) is a well known disease that had plagued the tropics relentlessly until an effective vaccine was developed. Although the yellow fever vaccine is relatively affordable and one dose protects for over ten years, its use has predominantly been for known endemic areas of the world and international travellers. Eastern and southern African states, have hitherto been free of epidemic yellow fever, hence routine YF vaccination is not a policy in these countries. The sudden emergence of YF in the Rift Valley in Kenya in 1992-1993, introduces new dimensions into the challenges of YF to eastern and southern African states. Isolation of a virus deemed to be native of the area is discussed in this article in the context of YF policy issues confronting the region. A case has been argued for the establishment of a network of active surveillance systems in the region backed by adequate laboratory YF expertise locally, regionally, and internationally.

Sanders EJ, Mugo P, Prins HAB, Wahome E, Thiong'o AN, Mwashigadi G, van der Elst EM, Omar A, Smith AD, Graham SM. 2014. Acute HIV-1 infection is as common as malaria in young febrile adults seeking care in coastal Kenya. AIDS, 28 (9), pp. 1357-1363. | Show Abstract | Read more

BACKGROUND: Febrile adults are usually not tested for acute HIV-1 infection (AHI) in Africa. We assessed a strategy to diagnose AHI among young adult patients seeking care. METHODS: Young adults (<30 years) who met predefined AHI criteria at care seeking, including fever, sexually transmitted disease symptoms, diarrhoea, body pains or multiple partners were referred from five pharmacies and screened at five health facilities. Prevalent HIV-1 was diagnosed by nationally recommended serial rapid HIV-1 testing. Willing HIV-1-negative patients were evaluated for AHI, defined as a positive p24 antigen test, and subsequent seroconversion or RNA detection. Febrile patients evaluated for AHI were also screened for malaria using a rapid test, with PCR confirmation of positives. RESULTS: In 3602 adults seeking care, overall HIV-1 prevalence was 3.9%: 7.6% (68/897) among patients meeting AHI criteria vs. 2.6% (71/2705) among those who did not (P < 0.001). AHI was diagnosed in five of 506 HIV-1-negative or discordant patients who met AHI risk criteria and were completely evaluated [prevalence 1.0%, 95% confidence interval (CI) 0.3-2.3%]. Of these five AHI cases, four were diagnosed among the 241 patients with fever (prevalence 1.7%, 95% CI 0.5-4.2%), vs. one among 265 non-febrile patients (prevalence 0.4%, 95% CI 0.0-2.0%, P = 0.1). Malaria was confirmed by PCR in four (1.7%) of the 241 febrile patients. CONCLUSION: AHI was as common as confirmed malaria in young febrile adults seeking care. An AHI detection strategy targeting young febrile adults seeking care at pharmacies and health facilities is feasible and should be considered as an HIV-prevention strategy in high-transmission settings.

Graham SM, Mugo P, Gichuru E, Thiong'o A, Macharia M, Okuku HS, van der Elst E, Price MA, Muraguri N, Sanders EJ. 2013. Adherence to antiretroviral therapy and clinical outcomes among young adults reporting high-risk sexual behavior, including men who have sex with men, in coastal Kenya. AIDS Behav, 17 (4), pp. 1255-1265. | Show Abstract | Read more

African men who have sex with men (MSM) face significant stigma and barriers to care. We investigated antiretroviral therapy (ART) adherence among high-risk adults, including MSM, participating in a clinic-based cohort. Survival analysis was used to compare attrition across patient groups. Differences in adherence, weight gain, and CD4 counts after ART initiation were assessed. Among 250 HIV-1-seropositive adults, including 108 MSM, 15 heterosexual men, and 127 women, patient group was not associated with attrition. Among 58 participants who were followed on ART, 40 % of MSM had less than 95 % adherence, versus 28.6 % of heterosexual men and 11.5 % of women. Although MSM gained less weight after ART initiation than women (adjusted difference -3.5 kg/year), CD4 counts did not differ. More data are needed on barriers to adherence and clinical outcomes among African MSM, to ensure that MSM can access care and derive treatment and prevention benefits from ART.

Sanders EJ, Okuku HS, Smith AD, Mwangome M, Wahome E, Fegan G, Peshu N, van der Elst EM, Price MA, McClelland RS, Graham SM. 2013. High HIV-1 incidence, correlates of HIV-1 acquisition, and high viral loads following seroconversion among MSM. AIDS, 27 (3), pp. 437-446. | Show Abstract | Read more

BACKGROUND: HIV-1 incidence estimates and correlates of HIV-1 acquisition in African MSM are largely unknown. METHODS: Since 2005, HIV-1-uninfected men who reported sex with men and women (MSMW) or sex with men exclusively (MSME) were followed at scheduled visits for collection of behavioural and clinical examination data and plasma for HIV-1 testing. Urethral or rectal secretions were collected from symptomatic men to screen for gonorrhoea. Poisson regression methods were used to estimate adjusted incidence rate ratios to explore associations between risk factors and incident HIV-1 infection. Plasma viral loads (PVLs) were assessed over 2 years following seroconversion. RESULTS: Overall HIV-1 incidence in 449 men was 8.6 [95% confidence interval (CI) 6.7-11.0] per 100 person-years. Incidence was 5.8 (95% CI 4.2-7.9) per 100 person-years among MSMW, and 35.2 (95% CI 23.8-52.1) per 100 person-years among MSME. Unprotected sex, receptive anal intercourse, exclusive sex with men, group sex, and gonorrhoea in the past 6 months were strongly associated with HIV-1 acquisition, adjusted for confounders. PVL in seroconverters was more than 4 log10 copies/ml at 230 (73.4%) of 313 visits in MSMW and 153 (75.0%) of 204 visits in MSME. CONCLUSION: HIV-1 incidence is very high among MSM in coastal Kenya, and many seroconverters maintain high PVL for up to 2 years after infection. Effective HIV-1 prevention interventions, including treatment as prevention, are urgently needed in this population.

Van der Elst EM, Mbogua J, Operario D, Mutua G, Kuo C, Mugo P, Kanungi J, Singh S, Haberer J, Priddy F, Sanders EJ. 2013. High acceptability of HIV pre-exposure prophylaxis but challenges in adherence and use: qualitative insights from a phase I trial of intermittent and daily PrEP in at-risk populations in Kenya. AIDS Behav, 17 (6), pp. 2162-2172. | Show Abstract | Read more

This paper used qualitative methods to explore experiences of men who have sex with men and female sex workers in Nairobi and Mtwapa, Kenya, who used oral pre-exposure prophylaxis (PrEP) for HIV prevention as part of a four-month trial of safety, acceptability and adherence. Fifty-one of 72 volunteers who took part in a randomized, placebo-controlled, blinded trial that compared daily and intermittent dosage of PrEP underwent qualitative assessments after completing the trial. Analyses identified three themes: (i) acceptability of PrEP was high, i.e. side effects were experienced early in the study but diminished over time, however characteristics of pills could improve comfort and use; (ii) social impacts such as stigma, rumors, and relationship difficulties due to being perceived as HIV positive were prevalent; (iii) adherence was challenged by complexities of daily life, in particular post-coital dosing adherence suffered from alcohol use around time of sex, mobile populations, and transactional sex work. These themes resonated across dosing regimens and gender, and while most participants favored the intermittent dosing schedule, those in the intermittent group noted particular challenges in adhering to the post-coital dose. Culturally appropriate and consistent counseling addressing these issues may be critical for PrEP effectiveness.

Cited:

181

Scopus

Sullivan PS, Carballo-Diéguez A, Coates T, Goodreau SM, McGowan I, Sanders EJ, Smith A, Goswami P, Sanchez J. 2012. Successes and challenges of HIV prevention in men who have sex with men The Lancet, 380 (9839), pp. 388-399. | Show Abstract | Read more

Men who have sex with men (MSM) have been substantially affected by HIV epidemics worldwide. Epidemics in MSM are re-emerging in many high-income countries and gaining greater recognition in many low-income and middle-income countries. Better HIV prevention strategies are urgently needed. Our review of HIV prevention strategies for MSM identified several important themes. At the beginning of the epidemic, stand-alone behavioural interventions mostly aimed to reduce unprotected anal intercourse, which, although somewhat efficacious, did not reduce HIV transmission. Biomedical prevention strategies reduce the incidence of HIV infection. Delivery of barrier and biomedical interventions with coordinated behavioural and structural strategies could optimise the effectiveness of prevention. Modelling suggests that, with sufficient coverage, available interventions are sufficient to avert at least a quarter of new HIV infections in MSM in diverse countries. Scale-up of HIV prevention programmes for MSM is difficult because of homophobia and bias, suboptimum access to HIV testing and care, and financial constraints.

Sanders EJ, Wahome E, Mwangome M, Thiong'o AN, Okuku HS, Price MA, Wamuyu L, Macharia M, McClelland RS, Graham SM. 2011. Most adults seek urgent healthcare when acquiring HIV-1 and are frequently treated for malaria in coastal Kenya. AIDS, 25 (9), pp. 1219-1224. | Show Abstract | Read more

BACKGROUND: Acute HIV-1 infection (AHI) may present with symptoms for which urgent healthcare is sought. However, little is known about healthcare seeking around the time of HIV-1 seroconversion in sub-Saharan Africa. METHODS: Review of clinical, counselling, treatment and laboratory records of previously HIV-1 seronegative at-risk adults, followed at monthly or 3-monthly visits, who seroconverted and enrolled in an AHI cohort. All HIV-seronegative plasma samples were tested for p24 antigen (p24) and stored preseroconversion samples for HIV-1 RNA (RNA). Factors associated with malaria treatment while acquiring HIV-1 were evaluated in multiple logistic regression. RESULTS: Sixty men and 12 women (95% of 75 seroconverters) were evaluated, including 43 (60%) with either p24-positive or RNA-positive or HIV-1 discordant rapid antibodies prior to seroconversion. Prior to diagnosis, 54 patients (75%) reported fever and 50 (69%) sought urgent care for symptomatic illness, including 23 (32%) who sought care in a nonresearch setting. Twenty-nine patients (40%) received presumptive malaria treatment. Only 24% of febrile patients were tested for malaria parasites. All documented smear results were negative. Malaria treatment was strongly associated with fever [adjusted odds ratio (aOR): 46, 95% confidence interval (CI): 3-725] and nonresearch setting (aOR: 5, 95% CI: 3-64). AHI was suspected in six (12%) patients who presented for urgent care during research evaluation. CONCLUSIONS: The majority of adults with AHI seek urgent healthcare. These individuals are often presumptively treated for malaria. Improved recognition of AHI in adults presenting for care may offer opportunities for optimizing HIV prevention strategies.

Tovanabutra S, Sanders EJ, Graham SM, Mwangome M, Peshu N, McClelland RS, Muhaari A, Crossler J, Price MA, Gilmour J et al. 2010. Evaluation of HIV type 1 strains in men having sex with men and in female sex workers in Mombasa, Kenya. AIDS Res Hum Retroviruses, 26 (2), pp. 123-131. | Show Abstract | Read more

We compared HIV-1 strains in incident and prevalent infections in a cohort of men having sex with men (MSM) and female sex workers (FSW) near Mombasa, Kenya and conducted a cross-sectional study of viral isolates from a sample of HIV-1-infected MSM and FSW in Kilifi, Coast Province, Kenya. RNA extracted from plasma of 13 MSM, 9 FSW, and one heterosexual male was amplified by nested RT-PCR and the products were directly sequenced. HIV-1 strains from 21 individuals were characterized with one or more complete genome sequences, and two were sequenced in the Nef gene. The envelope quasispecies was also studied in one individual. Among MSM, eight strains were subtype A and five were recombinant. There were two epidemiologically linked pairs of sequences; one pair was subtype A and the other pair was a complex AA2CD recombinant of identical structure. Another MSM was dually infected with DG recombinant strains of related, but nonidentical, structure. MSM also harbored AC and AD recombinant strains. The FSW harbored seven subtype A strains, an AD recombinant, and an AA2D strain related to CRF16_A2D. The one heterosexual male studied had a subtype A infection. This MSM epidemic in Kenya appears to be of local origin, harboring many strains typical of the broader Kenyan epidemic. Characteristics of a close social network were identified, with extended chains of transmission, novel recombinant strains possibly generated within the network, and a relatively high proportion of recombinant and dual infections.

Smith AD, Tapsoba P, Peshu N, Sanders EJ, Jaffe HW. 2009. Men who have sex with men and HIV/AIDS in sub-Saharan Africa. Lancet, 374 (9687), pp. 416-422. | Show Abstract | Read more

Globally, men who have sex with men (MSM) continue to bear a high burden of HIV infection. In sub-Saharan Africa, same-sex behaviours have been largely neglected by HIV research up to now. The results from recent studies, however, indicate the widespread existence of MSM groups across Africa, and high rates of HIV infection, HIV risk behaviour, and evidence of behavioural links between MSM and heterosexual networks have been reported. Yet most African MSM have no safe access to relevant HIV/AIDS information and services, and many African states have not begun to recognise or address the needs of these men in the context of national HIV/AIDS prevention and control programmes. The HIV/AIDS community now has considerable challenges in clarifying and addressing the needs of MSM in sub-Saharan Africa; homosexuality is illegal in most countries, and political and social hostility are endemic. An effective response to HIV/AIDS requires improved strategic information about all risk groups, including MSM. The belated response to MSM with HIV infection needs rapid and sustained national and international commitment to the development of appropriate interventions and action to reduce structural and social barriers to make these accessible.

Reniers G, Araya T, Davey G, Nagelkerke N, Berhane Y, Coutinho R, Sanders EJ. 2009. Steep declines in population-level AIDS mortality following the introduction of antiretroviral therapy in Addis Ababa, Ethiopia. AIDS, 23 (4), pp. 511-518. | Show Abstract | Read more

OBJECTIVES: Assessments of population-level effects of antiretroviral therapy (ART) programmes in Africa are rare. We use data from burial sites to estimate trends in adult AIDS mortality and the mitigating effects of ART in Addis Ababa. ART has been available since 2003, and for free since 2005. METHODS: To substitute for deficient vital registration, we use surveillance of burials at all cemeteries. We present trends in all-cause mortality, and estimate AIDS mortality (ages 20-64 years) from lay reports of causes of death. These lay reports are first used as a diagnostic test for the true cause of death. As reference standard, we use the cause of death established via verbal autopsy interviews conducted in 2004. The positive predictive value and sensitivity are subsequently used as anchors to estimate the number of AIDS deaths for the period 2001-2007. Estimates are compared with Spectrum projections. RESULTS: Between 2001 and 2005, the number of AIDS deaths declined by 21.9 and 9.3% for men and women, respectively. Between 2005 and 2007, the number of AIDS deaths declined by 38.2 for men and 42.9% for women. Compared with the expected number in the absence of ART, the reduction in AIDS deaths in 2007 is estimated to be between 56.8 and 63.3%, depending on the coverage of the burial surveillance. CONCLUSION: Five years into the ART programme, adult AIDS mortality has been reduced by more than half. Following the free provision of ART in 2005, the decline accelerated and became more sex balanced. Substantial AIDS mortality, however, persists.

HIV-1 specific cytotoxic T lymphocyte responses during acute HIV-1 infection with different subtypes in an African cohort

Acute HIV-1 infection (AHI) is the phase of HIV-1 infection immediately after acquisition, and is characterised by a burst of viraemia, during which 40%-90% of patients develop symptoms of the acute retroviral syndrome (ARS) and many seek medical care [1]. The early events of AHI, when the transmitted founder (T/F) virus encounters the immune system, are thought to be critical to determining the subsequent disease course in the absence of anti-retroviral therapy (ART). After the initial peak of ...

View project

158