Evelyne Kestelyn

Research Area: Global Health
Scientific Themes: Tropical Medicine & Global Health
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Evelyne Kestelyn is based in Ho Chi Minh City at the Wellcome Programme. She has been managing clinical trials since 2006 through institutions in Rwanda, the Netherlands and now Viet Nam. She joined OUCRU in January 2016 as Head of the Clinical Trials Unit. The Clinical Trials Unit manages research operations and governance for OUCRU, which includes Units in Viet Nam, Indonesia and Nepal. The CTU currently manages more than 70 active research projects at 65 collaborating institutions, run by hundreds of research staff. It leads and shares trial management systems, explores and addresses ethical issues in clinical research and contributes to clinical trials legislation.

There are no collaborations listed for this principal investigator.

Toan ND, Darton TC, Boinett CJ, Campbell JI, Karkey A, Kestelyn E, Thinh LQ, Mau NK, Thanh Tam PT, Nhan LNT et al. Clinical features, antimicrobial susceptibility patterns and genomics of bacteria causing neonatal sepsis in a children's hospital in Vietnam: protocol for a prospective observational study. BMJ Open, 8 (1), pp. e019611. | Show Abstract | Read more

INTRODUCTION: The clinical syndrome of neonatal sepsis, comprising signs of infection, septic shock and organ dysfunction in infants ≤4 weeks of age, is a frequent sequel to bloodstream infection and mandates urgent antimicrobial therapy. Bacterial characterisation and antimicrobial susceptibility testing is vital for ensuring appropriate therapy, as high rates of antimicrobial resistance (AMR), especially in low-income and middle-income countries, may adversely affect outcome. Ho Chi Minh City (HCMC) in Vietnam is a rapidly expanding city in Southeast Asia with a current population of almost 8 million. There are limited contemporary data on the causes of neonatal sepsis in Vietnam, and we hypothesise that the emergence of multidrug resistant bacteria is an increasing problem for the appropriate management of sepsis cases. In this study, we aim to investigate the major causes of neonatal sepsis and assess disease outcomes by clinical features, antimicrobial susceptibility profiles and genome composition. METHOD AND ANALYSIS: We will conduct a prospective observational study to characterise the clinical and microbiological features of neonatal sepsis in a major children's hospital in HCMC. All bacteria isolated from blood subjected to whole genome sequencing. We will compare clinical variables and outcomes between different bacterial species, genome composition and AMR gene content. AMR gene content will be assessed and stratified by species, years and contributing hospital departments. Genome sequences will be analysed to investigate phylogenetic relationships. ETHICS AND DISSEMINATION: The study will be conducted in accordance with the principles of the Declaration of Helsinki and the International Council on Harmonization Guidelines for Good Clinical Practice. Ethics approval has been provided by the Oxford Tropical Research Ethics Committee 35-16 and Vietnam Children's Hospital 1 Ethics Committee 73/GCN/BVND1. The findings will be disseminated at international conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN69124914; Pre-results.

Pokharel S, Basnyat B, Arjyal A, Mahat SP, Kc RK, Bhuju A, Poudyal B, Kestelyn E, Shrestha R, Phuong DNT et al. 2017. Co-trimoxazole versus azithromycin for the treatment of undifferentiated febrile illness in Nepal: study protocol for a randomized controlled trial. Trials, 18 (1), pp. 450. | Show Abstract | Read more

BACKGROUND: Undifferentiated febrile illness (UFI) includes typhoid and typhus fevers and generally designates fever without any localizing signs. UFI is a great therapeutic challenge in countries like Nepal because of the lack of available point-of-care, rapid diagnostic tests. Often patients are empirically treated as presumed enteric fever. Due to the development of high-level resistance to traditionally used fluoroquinolones against enteric fever, azithromycin is now commonly used to treat enteric fever/UFI. The re-emergence of susceptibility of Salmonella typhi to co-trimoxazole makes it a promising oral treatment for UFIs in general. We present a protocol of a randomized controlled trial of azithromycin versus co-trimoxazole for the treatment of UFI. METHODS/DESIGN: This is a parallel-group, double-blind, 1:1, randomized controlled trial of co-trimoxazole versus azithromycin for the treatment of UFI in Nepal. Participants will be patients aged 2 to 65 years, presenting with fever without clear focus for at least 4 days, complying with other study criteria and willing to provide written informed consent. Patients will be randomized either to azithromycin 20 mg/kg/day (maximum 1000 mg/day) in a single daily dose and an identical placebo or co-trimoxazole 60 mg/kg/day (maximum 3000 mg/day) in two divided doses for 7 days. Patients will be followed up with twice-daily telephone calls for 7 days or for at least 48 h after they become afebrile, whichever is later; by home visits on days 2 and 4 of treatment; and by hospital visits on days 7, 14, 28 and 63. The endpoints will be fever clearance time, treatment failure, time to treatment failure, and adverse events. The estimated sample size is 330. The primary analysis population will be all the randomized population and subanalysis will be repeated on patients with blood culture-confirmed enteric fever and culture-negative patients. DISCUSSION: Both azithromycin and co-trimoxazole are available in Nepal and are extensively used in the treatment of UFI. Therefore, it is important to know the better orally administered antimicrobial to treat enteric fever and other UFIs especially against the background of fluoroquinolone-resistant enteric fever. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02773407 . Registered on 5 May 2016.

van Nuil JI, Kestelyn E, Umutoni G, Mwambarangwe L, Umulisa MM, van de Wijgert J, Ravinetto R. 2017. Informed consent, community engagement, and study participation at a research site in Kigali, Rwanda. Dev World Bioeth, | Show Abstract | Read more

People enroll in medical research for many reasons ranging from decisions regarding their own or family members' health situation to broader considerations including access to health and financial resources. In socially vulnerable communities the choice to participate is often based on a risk-benefit assessment that goes beyond the medical aspects of the research, and considers the benefits received. In this qualitative study, we examined the motivations of Rwandan women to participate in a non-commercial collaborative research study examining the safety, acceptability, and adherence of a contraceptive vaginal ring in Rwanda juxtaposed with the perceptions of the research within the community. 351 women attended the screening visit, four were excluded because they were not able to complete the assessment of understanding. The remaining participants' ages ranged from 17 to 38 and 80% had primary level of education or below. 120 were enrolled. Findings highlighted motivations for joining the study that were relayed both formally by the clinic (e.g. testing and treatment) and informally by the community including the positive aspects of the ring. There were also some negative rumors circulating regarding the research site, likely from excluded participants who faced potential stigma based on that exclusion. It was understood by most participants that they were enrolled in a research study and participants actively sought out enrollment in the research for a variety of reasons. The experiences demonstrate that although inequalities in access to health care may create conflicting situations around the study, it is possible to form partnerships between a research center and participants/their partners, for research about reproductive health.

De Baetselier I, Mwambarangwe L, Cuylaerts V, Musengamana V, Agaba S, Kestelyn E, van de Wijgert J, Crucitti T. 2016. Evaluation of an enzymatic Chlamydia trachomatis point-of-care rapid assay in Rwanda: the BioChekSwab Rapid Test. Sex Transm Infect, 92 (6), pp. 430-432. | Show Abstract | Read more

OBJECTIVES: We evaluated the performance of an enzymatic point-of-care rapid test for Chlamydia trachomatis (CT) (the BioChekSwab CT Rapid Test, EnZtek Diagnostics, Rio Vista, California, USA), which detects CT's Peptidase 123CBV enzyme and provides a result 15 min after specimen collection. METHODS: Two endocervical swabs, including one BioChekSwab, per person were obtained from 137 women who participated in a reproductive health study in Rwanda. The BioChekSwab was processed according to the manufacturer's instructions. A substrate was squirted over the swab by the study physician immediately after collection, and another reagent was released over the swab tip at arrival in the laboratory. The test was considered positive if a blue colour developed within 2 min. The other regular flocked endocervical swab was processed at the Institute of Tropical Medicine (ITM), Belgium, using a testing algorithm: Abbott RealTime CT/Neisseria gonorrhoeae (NG) assay with the confirmation of positive results by an in-house real-time PCR assay. RESULTS: Of the 137 women, nine were CT positive by the testing algorithm. All nine positive results were missed by the BioChekSwab assay and four false-positive results were obtained. The sensitivity was therefore 0% (95% CI 0% to 33.6%) and the specificity was 96.9% (95% CI 92.2% to 99.1%). CONCLUSIONS: The BioChekSwab Rapid Test, although ISO13485 certified and Conformitée Européenne (CE) labelled, lacked any sensitivity in our setting.

Gautam R, Borgdorff H, Jespers V, Francis SC, Verhelst R, Mwaura M, Delany-Moretlwe S, Ndayisaba G, Kyongo JK, Hardy L et al. 2015. Correlates of the molecular vaginal microbiota composition of African women. BMC Infect Dis, 15 (1), pp. 86. | Show Abstract | Read more

BACKGROUND: Sociodemographic, behavioral and clinical correlates of the vaginal microbiome (VMB) as characterized by molecular methods have not been adequately studied. VMB dominated by bacteria other than lactobacilli may cause inflammation, which may facilitate HIV acquisition and other adverse reproductive health outcomes. METHODS: We characterized the VMB of women in Kenya, Rwanda, South Africa and Tanzania (KRST) using a 16S rDNA phylogenetic microarray. Cytokines were quantified in cervicovaginal lavages. Potential sociodemographic, behavioral, and clinical correlates were also evaluated. RESULTS: Three hundred thirteen samples from 230 women were available for analysis. Five VMB clusters were identified: one cluster each dominated by Lactobacillus crispatus (KRST-I) and L. iners (KRST-II), and three clusters not dominated by a single species but containing multiple (facultative) anaerobes (KRST-III/IV/V). Women in clusters KRST-I and II had lower mean concentrations of interleukin (IL)-1α (p < 0.001) and Granulocyte Colony Stimulating Factor (G-CSF) (p = 0.01), but higher concentrations of interferon-γ-induced protein (IP-10) (p < 0.01) than women in clusters KRST-III/IV/V. A lower proportion of women in cluster KRST-I tested positive for bacterial sexually transmitted infections (STIs; ptrend = 0.07) and urinary tract infection (UTI; p = 0.06), and a higher proportion of women in clusters KRST-I and II had vaginal candidiasis (ptrend = 0.09), but these associations did not reach statistical significance. Women who reported unusual vaginal discharge were more likely to belong to clusters KRST-III/IV/V (p = 0.05). CONCLUSION: Vaginal dysbiosis in African women was significantly associated with vaginal inflammation; the associations with increased prevalence of STIs and UTI, and decreased prevalence of vaginal candidiasis, should be confirmed in larger studies.

Schurmans C, De Baetselier I, Kestelyn E, Jespers V, Delvaux T, Agaba SK, van Loen H, Menten J, van de Wijgert J, Crucitti T, RING PLUS study group. 2015. The ring plus project: safety and acceptability of vaginal rings that protect women from unintended pregnancy. BMC Public Health, 15 (1), pp. 348. | Show Abstract | Read more

BACKGROUND: Research is ongoing to develop multipurpose vaginal rings to be used continuously for contraception and to prevent Human Immunodeficiency Virus (HIV) infection. Contraceptive vaginal rings (CVRs) are available in a number of countries and are most of the time used intermittently i.e. three weeks out of a 4-week cycle. Efficacy trials with a dapivirine-containing vaginal ring for HIV prevention are ongoing and plans to develop multi-purpose vaginal rings for prevention of both HIV and pregnancy have been elaborated. In contrast with the CVRs, multi-purpose vaginal rings will have to be used continuously. Women who continuously use a CVR will no longer have menses. Furthermore, some safety aspects of CVR use have never been studied in-depth in the past, such as the impact of the vaginal ring on the vaginal microbiota, biofilm formation and induction of inflammation. We studied acceptability and these novel aspects of safety in Rwandan women. Although significant progress has been made over the past decade, Rwanda still has a high unmet need for contraception (with 47% unplanned births) and a generalized HIV epidemic, and CVRs are not yet available. METHODS: We will conduct an open label, single centre, randomized controlled trial. A total of 120 HIV-negative women will be randomized to intermittent CVR use (to allow menstruation) or continuous CVR use. Women will be followed for a maximum of 14 weeks. In parallel, we will conduct a qualitative study using in-depth interview and focus group discussion methodology. DISCUSSION: In addition to evaluating the safety and acceptability of intermittent and continuous CVR use in Rwandan women, we hope that our findings will inform the development of future multipurpose vaginal rings, will prepare Rwandan study populations for future clinical trials of multipurpose vaginal rings, and will pave the way for introduction of CVRs on African markets. TRIAL REGISTRATION: Clinicaltrials.gov NCT01796613 . Registered 14 February 2013.

Jespers V, Crucitti T, Menten J, Verhelst R, Mwaura M, Mandaliya K, Ndayisaba GF, Delany-Moretlwe S, Verstraelen H, Hardy L et al. 2014. Prevalence and correlates of bacterial vaginosis in different sub-populations of women in sub-Saharan Africa: a cross-sectional study. PLoS One, 9 (10), pp. e109670. | Show Abstract | Read more

BACKGROUND: Clinical development of vaginally applied products aimed at reducing the transmission of HIV and other sexually transmitted infections, has highlighted the need for a better characterisation of the vaginal environment. We set out to characterise the vaginal environment in women in different settings in sub-Saharan Africa. METHODS: A longitudinal study was conducted in Kenya, Rwanda and South-Africa. Women were recruited into pre-defined study groups including adult, non-pregnant, HIV-negative women; pregnant women; adolescent girls; HIV-negative women engaging in vaginal practices; female sex workers; and HIV-positive women. Consenting women were interviewed and underwent a pelvic exam. Samples of vaginal fluid and a blood sample were taken and tested for bacterial vaginosis (BV), HIV and other reproductive tract infections (RTIs). This paper presents the cross-sectional analyses of BV Nugent scores and RTI prevalence and correlates at the screening and the enrolment visit. RESULTS: At the screening visit 38% of women had BV defined as a Nugent score of 7-10, and 64% had more than one RTI (N. gonorrhoea, C. trachomatis, T. vaginalis, syphilis) and/or Candida. At screening the likelihood of BV was lower in women using progestin-only contraception and higher in women with more than one RTI. At enrolment, BV scores were significantly associated with the presence of prostate specific antigen (PSA) in the vaginal fluid and with being a self-acknowledged sex worker. Further, sex workers were more likely to have incident BV by Nugent score at enrolment. CONCLUSIONS: Our study confirmed some of the correlates of BV that have been previously reported but the most salient finding was the association between BV and the presence of PSA in the vaginal fluid which is suggestive of recent unprotected sexual intercourse.

Van Nuil JI, Mutwa P, Asiimwe-Kateera B, Kestelyn E, Vyankandondera J, Pool R, Ruhirimbura J, Kanakuze C, Reiss P, Geelen SPM et al. 2014. "Let's talk about sex": a qualitative study of Rwandan adolescents' views on sex and HIV. PLoS One, 9 (8), pp. e102933. | Show Abstract | Read more

OBJECTIVE: This qualitative study explored the views and experiences of adolescents with perinatally acquired HIV in Kigali, Rwanda, regarding sex, love, marriage, children and hope for the future. DESIGN: The study enrolled 42 adolescents who had received combination antiretroviral therapy for at least 12 months, and a selection of their primary caregivers. Study methods included 3 multiple day workshops consisting of role-playing and focus group discussions (FGDs) with adolescents, 8 in-depth interviews with adolescents, and one FGD with caregivers. RESULTS: The adolescents reported experiencing similar sexual needs and dilemmas as most other adolescents, but with an added layer of complexity due to fears related to HIV transmission and/or rejection by partners. They desired more advice from their parents/caregivers on these topics. Although they struggled with aspects of sex, love, marriage and having children, most agreed that they would find love, be married and have children in the future. The two most discussed HIV-related anxieties were how and when to disclose to a (potential) sex/marriage partner and whether to have children. However, most adolescents felt that they had a right to love and be loved, and were aware of prevention-of-mother-to-child-transmission (PMTCT) options in Rwanda. Adolescents generally spoke about their future role in society in a positive manner. CONCLUSION: Strengthening the life skills of HIV-positive adolescents, especially around HIV disclosure and reduction of HIV transmission, as well as the support skills of parents/caregivers, may not only reduce onward HIV transmission but also improve quality of life by reducing anxiety.

Ndayisaba G, Verwijs MC, van Eeckhoudt S, Gasarabwe A, Hardy L, Borgdorff H, Kestelyn E, Jespers VA, van de Wijgert J. 2013. Feasibility and acceptability of a novel cervicovaginal lavage self-sampling device among women in Kigali, Rwanda. Sex Transm Dis, 40 (7), pp. 552-555. | Show Abstract | Read more

The Delphi Screener is a novel cervicovaginal lavage self-sampling device. Sixty women in Kigali (Rwanda) assessed the Screener at 2 consecutive visits. Between the visits, ease of use improved, reported difficulties decreased, and the collected sample weight increased. Most women preferred self-collection over a speculum examination.

Veldhuijzen NJ, van Steijn M, Nyinawabega J, Kestelyn E, Uwineza M, Vyankandondera J, van de Wijgert JHHM. 2013. Prevalence of sexually transmitted infections, genital symptoms and health-care seeking behaviour among HIV-negative female sex workers in Kigali, Rwanda. Int J STD AIDS, 24 (2), pp. 139-143. | Show Abstract | Read more

Timely diagnosis and treatment of sexually transmitted infections (STIs) is often hampered by the lack of symptoms, inadequate diagnostics and/or poor availability, accessibility and quality of treatment in resource-limited settings. Female sex workers (FSW) are highly vulnerable for HIV and key transmitters of STIs. Among FSW (n = 400) participating in a prospective HIV incidence study in Kigali, Rwanda, only 15% (17/116) of women with laboratory-diagnosed non-ulcerative STIs at baseline reported symptoms. Only 27% (20/74) of women self-reporting genital symptoms sought care at enrolment, and 39% (46/117) of women with self-reported genital symptoms during follow-up. During focus group discussions, FSW considered treatment-seeking and partner notification important. Shame and feeling disrespected by doctors or other health-care workers were identified as barriers to seeking health care. A comprehensive STI control programme targeting both symptomatic and asymptomatic FSW should be considered in this setting.

Mutwa PR, Van Nuil JI, Asiimwe-Kateera B, Kestelyn E, Vyankandondera J, Pool R, Ruhirimbura J, Kanakuze C, Reiss P, Geelen S et al. 2013. Living situation affects adherence to combination antiretroviral therapy in HIV-infected adolescents in Rwanda: a qualitative study. PLoS One, 8 (4), pp. e60073. | Show Abstract | Read more

INTRODUCTION: Adherence to combination antiretroviral therapy (cART) is vital for HIV-infected adolescents for survival and quality of life. However, this age group faces many challenges to remain adherent. We used multiple data sources (role-play, focus group discussions (FGD), and in-depth interviews (IDI)) to better understand adherence barriers for Rwandan adolescents. Forty-two HIV positive adolescents (ages 12-21) and a selection of their primary caregivers were interviewed. All were perinatally-infected and received (cART) for ≥ 12 months. Topics discussed during FGDs and IDIs included learning HIV status, disclosure and stigma, care and treatment issues, cART adherence barriers. RESULTS: Median age was 17 years, 45% female, 45% orphaned, and 48% in boarding schools. We identified three overarching but inter-related themes that appeared to influence adherence. Stigma, perceived and experienced, and inadvertent disclosure of HIV status hampered adolescents from obtaining and taking their drugs, attending clinic visits, carrying their cARTs with them in public. The second major theme was the need for better support, in particular for adolescents with different living situations, (orphanages, foster-care, and boarding schools). Lack of privacy to keep and take medication came out as major barrier for adolescents living in congested households, as well the institutionalization of boarding schools where privacy is almost non-existent. The third important theme was the desire to be 'normal' and not be recognized as an HIV-infected individual, and to have a normal life not perturbed by taking a regimen of medications or being forced to disclose where others would treat them differently. CONCLUSIONS: We propose better management of HIV-infected adolescents integrated into boarding school, orphanages, and foster care; training of school-faculty on how to support students and allow them privacy for taking their medications. To provide better care and support, HIV programs should stimulate caregivers of HIV-infected adolescents to join them for their clinic visits.

Ingabire MC, Mitchell K, Veldhuijzen N, Umulisa MM, Nyinawabega J, Kestelyn E, Van Steijn M, Van De Wijgert J, Pool R. 2012. Joining and leaving sex work: experiences of women in Kigali, Rwanda. Cult Health Sex, 14 (9), pp. 1037-1047. | Show Abstract | Read more

Although sex work can bring significant economic benefit there are serious downsides, not least vulnerability to adverse sexual health outcomes. Focus-groups discussions and in-depth interviews were conducted with 70 female sex workers to explore the context in which they started sex work, their motivations to leave, and their experiences of trying to leave. The pathway to becoming a sex worker was underscored by poverty, with disruptive events leading to increasing vulnerability and increasingly difficult life choices. A sizeable minority of women became sex workers while working as house-girls, a position associated with financial, physical and sexual vulnerability. The majority of participants were still working as sex workers, citing financial reasons for not leaving. Motivations to leave sex work included experiencing a frightening incident, peer pressure and concerns about dependent children. Those who left often described a change in their financial circumstances that enabled them to leave. Some had left but had returned to sex work following a financial crisis or because they found their new life too hard. House-girls are particularly vulnerable and therefore an appropriate focus for prevention. Programmes assisting women to leave need to include financial safety nets so that a time of financial difficulty does not necessitate a return to sex work.

Wall K, Karita E, Nizam A, Bekan B, Sardar G, Casanova D, Joseph Davey D, De Clercq F, Kestelyn E, Bayingana R et al. 2012. Influence network effectiveness in promoting couples' HIV voluntary counseling and testing in Kigali, Rwanda. AIDS, 26 (2), pp. 217-227. | Show Abstract | Read more

OBJECTIVE: To identify predictors of promotion of couples' HIV voluntary counseling and testing (CVCT) in Kigali, Rwanda. DESIGN: Analysis of CVCT promotional agent [influential network leaders (INLs), influential network agents (INAs)], and couple/invitation-level predictors of CVCT uptake. METHODS: Number of invitations and couples tested were evaluated by INL, INA, and couple/contextual factors. Multivariable logistic regression accounting for two-level clustering analyzed factors predictive of couples' testing. RESULTS: Twenty-six INLs recruited and mentored 118 INAs who delivered 24 991 invitations. 4513 couples sought CVCT services after invitation. INAs distributed an average of 212 invitations resulting in an average of 38 couples tested/agent. Characteristics predictive of CVCT in multivariate analyses included the invitee and INA being socially acquainted [adjusted odds ratio (aOR) = 1.4; 95% confidence interval (CI) 1.2-1.6]; invitations delivered after public endorsement (aOR = 1.3; 95% CI 1.1-1.5); and presence of a mobile testing unit (aOR = 1.4; 95% CI 1.0-2.0). In stratified analyses, predictors significant among cohabiting couples included invitation delivery to the couple (aOR = 1.2; 95% CI 1.0-1.4) and in the home (aOR = 1.3; 95% CI 1.1-1.4), whereas among noncohabiting couples, predictors included invitations given by unemployed INAs (aOR = 1.7; 95% CI 1.1-2.7). Cohabiting couples with older men were more likely to test, whereas younger age was associated with testing among men in noncohabiting unions. CONCLUSIONS: Invitations distributed by influential people were successful in prompting couples to seek joint HIV testing, particularly if the invitation was given in the home to someone known to the INA and accompanied by a public endorsement of CVCT. Mobile units also increased the number of couples tested. Country-specific strategies to promote CVCT programs are needed to reduce HIV transmission among those at highest risk for HIV in sub-Saharan Africa.

Braunstein SL, van de Wijgert JH, Vyankandondera J, Kestelyn E, Ntirushwa J, Nash D. 2012. Risk Factor Detection as a Metric of STARHS Performance for HIV Incidence Surveillance Among Female Sex Workers in Kigali, Rwanda. Open AIDS J, 6 (1), pp. 112-121. | Show Abstract | Read more

BACKGROUND: The epidemiologic utility of STARHS hinges not only on producing accurate estimates of HIV incidence, but also on identifying risk factors for recent HIV infection. METHODS: As part of an HIV seroincidence study, 800 Rwandan female sex workers (FSW) were HIV tested, with those testing positive further tested by BED-CEIA (BED) and AxSYM Avidity Index (Ax-AI) assays. A sample of HIV-negative (N=397) FSW were followed prospectively for HIV seroconversion. We compared estimates of risk factors for: 1) prevalent HIV infection; 2) recently acquired HIV infection (RI) based on three different STARHS classifications (BED alone, Ax-AI alone, BED/Ax-AI combined); and 3) prospectively observed seroconversion. RESULTS: There was mixed agreement in risk factors between methods. HSV-2 coinfection and recent STI treatment were associated with both prevalent HIV infection and all three measures of recent infection. A number of risk factors were associated only with prevalent infection, including widowhood, history of forced sex, regular alcohol consumption, prior imprisonment, and current breastfeeding. Number of sex partners in the last 3 months was associated with recent infection based on BED/Ax-AI combined, but not other STARHS-based recent infection outcomes or prevalent infection. Risk factor estimates for prospectively observed seroconversion differed in magnitude and direction from those for recent infection via STARHS. CONCLUSIONS: Differences in risk factor estimates by each method could reflect true differences in risk factors between the prevalent, recently, or newly infected populations, the effect of study interventions (among those followed prospectively), or assay misclassification. Similar investigations in other populations/settings are needed to further establish the epidemiologic utility of STARHS for identifying risk factors, in addition to incidence rate estimation.

Braunstein SL, Umulisa M-M, Veldhuijzen NJ, Kestelyn E, Ingabire CM, Nyinawabega J, van de Wijgert JHHM, Nash D. 2011. HIV diagnosis, linkage to HIV care, and HIV risk behaviors among newly diagnosed HIV-positive female sex workers in Kigali, Rwanda. J Acquir Immune Defic Syndr, 57 (4), pp. e70-e76. | Show Abstract | Read more

OBJECTIVE: To evaluate linkage-to-care, sexual behavior change, and psychosocial experiences among newly HIV-diagnosed female sex workers (FSWs) in Rwanda. METHODS: FSWs (n = 800) with unknown serostatus were screened for HIV during 2007/2008. Women testing HIV positive (n = 192) were referred to care and asked to return for interviews and laboratory testing 12-36 months postdiagnosis. One hundred fourty-one women (73%) returned for the postdiagnosis visit. RESULTS: Median CD4 count at diagnosis was 460 cells per microliter [interquartile range (IQR): 308-628], with 32% eligible for antiretroviral therapy (ART) per national CD4 criteria (median CD4: 235, IQR: 152-303). Postdiagnosis, 92% of women reported having disclosed their HIV status to a friend or relative, 85% reported having enrolled in HIV care (median 30 days after diagnosis, IQR: 7-360), including 89% among ART-eligible women. Among ART-eligible women in care, 87% had initiated ART, with a median follow-up CD4 count of 354 cells per microliter (IQR: 213-456). Women who did not initiate ART experienced a 6-month CD4 count change of -14 cells per microliter (IQR: -41 to 13). Three-quarters of women reported reduced sexual risk behavior postdiagnosis, with only 64% continuing to identify as FSWs. However, 53% reported past month condom use only "sometimes." CONCLUSIONS: Timely linkage to care and ART uptake were high in this group of Rwandan FSWs. However, risky sexual behaviors remained common after enrollment in care. HIV-positive FSWs are an important and receptive group for targeted efforts to increase HIV diagnosis and linkage to care/treatment. Once in care, intensified and sustained HIV prevention education is necessary.

Braunstein SL, Ingabire CM, Kestelyn E, Uwizera AU, Mwamarangwe L, Ntirushwa J, Nash D, Veldhuijzen NJ, Nel A, Vyankandondera J, van de Wijgert JHHM. 2011. High human immunodeficiency virus incidence in a cohort of Rwandan female sex workers. Sex Transm Dis, 38 (5), pp. 385-394. | Show Abstract | Read more

BACKGROUND: Measurement of human immunodeficiency virus(HIV) incidence among female sex workers in Rwanda is a key part of preparing for HIV prevention trials. METHODS: HIV-negative, nonpregnant female sex workers (N =397) were tested for HIV-1, sexually transmitted infections, and pregnancy quarterly for 12 months, and again at a 1-time year 2 visit. Additional women (N=156) were tested for HIV at baseline and 6 to 12 months thereafter in a parallel study. RESULTS: A total of 19 participants seroconverted during follow-up,with 13 in the first 12 months. The 12-month HIV incidence rate (IR)was 3.5 (95% confidence interval: 1.6, 5.4) per 100 person-years (PY).There was a nonsignificant downward trend from 4.6/100 PY (1.6, 7.7)in the first 6 months to 2.2 (0.1, 4.4) in the second 6 months (IR ratio:2.1 [95% confidence interval: 0.7, 7.8]). The year 2 IR was 2.1 (0.4,3.7), and the HIV IR in the parallel study (in the absence of frequent study visits) was 3.3/100 PY (0, 7.0). HIV testing history, lifetime pregnancies, recent initiation of sex work, gonorrhea, syphilis, and change in reproductive intentions were associated with incident HIV infection. Incidence of pregnancy, herpes simplex virus-type 2,trichomoniasis, gonorrhea, chlamydia, and syphilis per 100 PY were as follows: 26.3 (21.9, 30.7), 8.7 (4.0, 13.4), 16.9 (12.7, 21.1), 12.1 (8.2,15.9), 8.1 (5.1, 11.2), and 6.2 (3.7, 8.7). CONCLUSIONS: The HIV/sexually transmitted infections burden int his group was high. HIV IR was highest in the first 6 months of the cohort, and in the parallel study in which there were no risk-reduction procedures. HIV prevention and family planning interventions are needed.

Veldhuijzen NJ, Braunstein SL, Vyankandondera J, Ingabire C, Ntirushwa J, Kestelyn E, Tuijn C, Wit FW, Umutoni A, Uwineza M et al. 2011. The epidemiology of human papillomavirus infection in HIV-positive and HIV-negative high-risk women in Kigali, Rwanda. BMC Infect Dis, 11 (1), pp. 333. | Show Abstract | Read more

BACKGROUND: The prevalence, incidence and persistence of human papillomavirus (HPV) types in sub-Saharan Africa are not well established. The objectives of the current study are to describe (predictors of) the epidemiology of HPV among high-risk women in Kigali, Rwanda. METHODS: HIV-negative, high-risk women were seen quarterly for one year, and once in Year 2. HIV serostatus, clinical, and behavioral information were assessed at each visit, HPV types at Month 6 and Year 2, and other sexually transmitted infections (STI) at selected visits. HPV prevalence was also assessed in HIV-positive, high-risk women. RESULTS: Prevalence of any HPV was 47.0% in HIV-negative women (median age 25 years) compared to 72.2% in HIV-positive women (median age 27 years; OR 2.9, 95% CI 1.9-4.6). Among HIV-negative women, cumulative incidence of high-risk (HR)-HPV was 28.0% and persistence 32.0% after a mean period of 16.6 and 16.9 months, respectively. Prior Chlamydia trachomatis and Neisseria gonorrhoeae infection, concurrent low-risk (LR)-HPV infection and incident HSV-2 were associated with HR-HPV prevalence among HIV-negative women; prior C. trachomatis infection and co-infection with LR-HPV and HPV16-related HPV types with HR-HPV acquisition. HPV16-related types were the most prevalent and persistent. CONCLUSIONS: High HPV prevalence, incidence and persistence were found among high-risk women in Kigali. HPV52 had the highest incidence; and, together with HPV33 and HPV58, were strongly associated with acquisition of other HR-HPV types in HIV-negative women.

Mai NT, Dobbs N, Phu NH, Colas RA, Thao LT, Thuong NT, Nghia HD, Hanh NH, Hang NT, Heemskerk AD et al. 2018. A randomised double blind placebo controlled phase 2 trial of adjunctive aspirin for tuberculous meningitis in HIV-uninfected adults. Elife, 7 | Show Abstract | Read more

Background Adjunctive dexamethasone reduces mortality from tuberculous meningitis (TBM) but not disability, which is associated with brain infarction. We hypothesised that aspirin prevents TBM-related brain infarction through its anti-thrombotic, anti-inflammatory, and pro-resolution properties.MethodsWe conducted a randomised controlled trial in HIV-uninfected adults with TBM of daily aspirin 81mg or 1000mg, or placebo, added to the first 60 days of anti-tuberculosis drugs and dexamethasone (NCT02237365). The primary safety endpoint was gastro-intestinal or cerebral bleeding by 60 days; the primary efficacy endpoint was new brain infarction confirmed by magnetic resonance imaging or death by 60 days. Secondary endpoints included 8-month survival and neuro-disability; the number of grade 3&4 and serious adverse events; and cerebrospinal fluid (CSF) inflammatory lipid mediator profiles.Findings41 participants were randomised to placebo, 39 to aspirin 81mg/day, and 40 to aspirin 1000mg/day between October 2014 and May 2016. TBM was proven microbiologically in 92/120(76.7%) and baseline brain imaging revealed {greater than or equal to}1 infarct in 40/114(35.1%) participants. The primary safety outcome occurred in 5/36(13.9%) given placebo, and in 8/35(22.9%) and 8/40(20.0%) given 81mg and 1000mg aspirin respectively (P=0.59). The primary efficacy outcome occurred in 11/38(28.9%) given placebo, 8/36(22.2%) given aspirin 81mg, and 6/38(15.8%) given 1000mg aspirin (P=0.40). Planned subgroup analysis showed a significant interaction between aspirin treatment effect and diagnostic category (Pheterogeneity=0.01) and suggested a potential reduction in new infarcts and deaths by day 60 in the aspirin treated participants with microbiologically confirmed TBM (11/32(34.4%) events in placebo vs. 4/27(14.8%) in aspirin 81 mg vs. 3/28 (10.7%) in aspirin 1000mg; P=0.06). CSF analysis demonstrated aspirin dose-dependent inhibition of thromboxane A2and upregulation of pro-resolving CSF protectins.InterpretationThe addition of aspirin to dexamethasone may improve outcomes from TBM and warrants investigation in a large phase 3 trial. CLINICAL TRIAL REGISTRATION: NCT02237365.