Dr Thuy Le

Research Area: Global Health
Scientific Themes: Tropical Medicine & Global Health and Immunology & Infectious Disease
Keywords: HIV, HIV-associated opportunistic infections, Drug resistance, Tuberculosis and Mycosis

My research interest is in reducing disease burden, improving diagnostics and treatment of HIV-associated infections through epidemiology, laboratory technologies and clinical trials. My major disease areas of interest are HIV-associated opportunistic infections, specifically Penicillium marneffei infection, HIV drug resistance, and HIV-HCV coinfection. I collaborate closely with major hospitals providing HIV care throughout Vietnam. Currently I am the Principal Investigator of 2 ongoing multi-center clinical trials, one comparing amphotericin B and itraconazole in the treatment of HIV-associated penicilliosis, the other to evaluate the safety of raltegravir compared to efavirenz in HIV-HCV coinfection. I also lead and collaborate on studies to understand disease epidemiology, identifying risk factors for infections, and improving diagnostics and treatment of penicilliosis.

There are no collaborations listed for this principal investigator.

Le T, Thwaites G, Wolbers M. 2017. Itraconazole or Amphotericin B for Talaromycosis. N Engl J Med, 377 (14), pp. 1403. | Read more

Le T, Kinh NV, Cuc NTK, Tung NLN, Lam NT, Thuy PTT, Cuong DD, Phuc PTH, Vinh VH, Hanh DTH et al. 2017. A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis. N Engl J Med, 376 (24), pp. 2329-2340. | Show Abstract | Read more

BACKGROUND: Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking. METHODS: In this open-label, noninferiority trial, we randomly assigned 440 HIV-infected adults who had talaromycosis, confirmed by either microscopy or culture, to receive either intravenous amphotericin B deoxycholate (amphotericin) (219 patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days, followed by 400 mg per day, for 11 days; thereafter, all the patients received maintenance therapy with itraconazole. The primary outcome was all-cause mortality at week 2. Secondary outcomes included all-cause mortality at week 24, the time to clinical resolution of talaromycosis, early fungicidal activity, relapse of talaromycosis, development of the immune reconstitution inflammatory syndrome (IRIS), and the side-effect profile. RESULTS: The risk of death at week 2 was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval [CI], -3.9 to 5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3% in the amphotericin group and 21.0% in the itraconazole group (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with amphotericin was associated with significantly faster clinical resolution and fungal clearance and significantly lower rates of relapse and IRIS than itraconazole. The patients who received amphotericin had significantly higher rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, and anemia than patients in the itraconazole group. CONCLUSIONS: Amphotericin was superior to itraconazole as initial treatment for talaromycosis with respect to 6-month mortality, clinical response, and fungicidal activity. (Funded by the Medical Research Council and others; IVAP Current Controlled Trials number, ISRCTN59144167 .).

Birger RB, Le T, Kouyos RD, Grenfell BT, Hallett TB. 2017. The impact of HCV therapy in a high HIV-HCV prevalence population: A modeling study on people who inject drugs in Ho Chi Minh City, Vietnam. PLoS One, 12 (5), pp. e0177195. | Show Abstract | Read more

BACKGROUND: Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) coinfection is a major global health problem especially among people who inject drugs (PWID), with significant clinical implications. Mathematical models have been used to great effect to shape HIV care, but few have been proposed for HIV/HCV. METHODS: We constructed a deterministic compartmental ODE model that incorporated layers for HIV disease progression, HCV disease progression and PWID demography. Antiretroviral therapy (ART) and Methadone Maintenance Therapy (MMT) scale-ups were modeled as from 2016 and projected forward 10 years. HCV treatment roll-out was modeled beginning in 2026, after a variety of MMT scale-up scenarios, and projected forward 10 years. RESULTS: Our results indicate that scale-up of ART has a major impact on HIV though not on HCV burden. MMT scale-up has an impact on incidence of both infections. HCV treatment roll-out has a measurable impact on reductions of deaths, increasing multifold the mortality reductions afforded by just ART/MMT scale-ups. CONCLUSION: HCV treatment roll-out can have major and long-lasting effects on averting PWID deaths on top of those averted by ART/MMT scale-up. Efficient intervention scale-up of HCV alongside HIV interventions is critical in Vietnam.

Limper AH, Adenis A, Le T, Harrison TS. 2017. Fungal infections in HIV/AIDS. Lancet Infect Dis, 17 (11), pp. e334-e343. | Show Abstract | Read more

Fungi are major contributors to the opportunistic infections that affect patients with HIV/AIDS. Systemic infections are mainly with Pneumocystis jirovecii (pneumocystosis), Cryptococcus neoformans (cryptococcosis), Histoplasma capsulatum (histoplasmosis), and Talaromyces (Penicillium) marneffei (talaromycosis). The incidence of systemic fungal infections has decreased in people with HIV in high-income countries because of the widespread availability of antiretroviral drugs and early testing for HIV. However, in many areas with high HIV prevalence, patients present to care with advanced HIV infection and with a low CD4 cell count or re-present with persistent low CD4 cell counts because of poor adherence, resistance to antiretroviral drugs, or both. Affordable, rapid point-of-care diagnostic tests (as have been developed for cryptococcosis) are urgently needed for pneumocystosis, talaromycosis, and histoplasmosis. Additionally, antifungal drugs, including amphotericin B, liposomal amphotericin B, and flucytosine, need to be much more widely available. Such measures, together with continued international efforts in education and training in the management of fungal disease, have the potential to improve patient outcomes substantially.

Thao VP, Quang VM, Vinh Chau NV, Day J, Thwaites G, Le T. 2017. A4 The transmission dynamics over ten years of human immunodeficiency virus type 1 in Vietnam. Virus Evol, 3 (Suppl 1), | Read more

Greene G, Sriruttan C, Le T, Chiller T, Govender NP. 2017. Looking for fungi in all the right places: screening for cryptococcal disease and other AIDS-related mycoses among patients with advanced HIV disease. Curr Opin HIV AIDS, 12 (2), pp. 139-147. | Show Abstract | Read more

PURPOSE OF REVIEW: As HIV treatment programmes scale up to meet the UNAIDS 90-90-90 goals, care must be taken to start antiretroviral treatment safely in patients with advanced disease (CD4 counts <200 cells/μl) who are simultaneously at risk for opportunistic infections and immune reconstitution inflammatory syndrome. Invasive fungal diseases pose a great threat at this critical time point, though the development of inexpensive and highly accurate rapid diagnostic tests has changed the approach HIV programmes are taking to reduce the high mortality associated with these opportunistic infections. This article summarizes recent advances and findings in fungal opportunistic infection diagnostics with a focus on screening to prevent cryptococcal meningitis. RECENT FINDINGS: Cryptococcal antigen (CrAg) screening using a lateral flow assay platform is cost-effective and feasible to implement as either a laboratory reflex or point-of-care test. Recent CrAg screening pilots have elucidated the varying prevalence of cryptococcal antigenemia across geographic regions, which may aid programme planning. Evidence from recently completed clinical trials provides a strong motivation for the use of CrAg titer to refine treatment options for patients with subclinical cryptococcal disease. SUMMARY: Although several operational barriers to programme effectiveness still need to be addressed, the utility of CrAg screening using inexpensive and accurate antigen assays has been demonstrated in real-world HIV programmes, paving the way for development and testing of other fungal opportunistic infection screening strategies and for an integrated advanced HIV disease testing package to reduce AIDS mortality and ensure safe antiretroviral treatment initiation.

Thanh NT, Vinh LD, Liem NT, Shikuma C, Day JN, Thwaites G, Le T. 2016. Clinical features of three patients with paradoxical immune reconstitution inflammatory syndrome associated with Talaromyces marneffei infection Medical Mycology Case Reports, | Read more

Hien HTA, Thanh TT, Thu NTM, Nguyen A, Thanh NT, Lan NPH, Simmons C, Shikuma C, Chau NVV, Thwaites G, Le T. 2016. Development and evaluation of a real-time polymerase chain reaction assay for the rapid detection of Talaromyces marneffei MP1 gene in human plasma. Mycoses, 59 (12), pp. 773-780. | Show Abstract | Read more

Penicilliosis caused by Talaromyces marneffei is a common AIDS-defining illness in South and Southeast Asia. Diagnosis is based on culture which can take up to 14 days for identification, leading to treatment delay and increased mortality. We developed a TaqMan real-time PCR assay targeting the MP1 gene encoding an abundant cell wall protein specific to T. marneffei. The assay's performance was evaluated in MP1-containing plasmids, clinical isolates, and plasma from HIV-infected patients with and without penicilliosis. The assay consistently detected 10 copies of MP1-containing plasmids per reaction and 100 T. marneffei yeast cells per millilitre plasma. There were no amplification with seven other Penicillium species and six other HIV-associated fungal pathogens tested. The assay was evaluated in 70 patients with AIDS: 50 patients with culture-confirmed penicilliosis and 20 patients with opportunistic infections other than penicilliosis. The diagnostic sensitivity was 70.4% (19/27, 95% CI: 51.5-84.1%) and 52.2% (12/23, 95% CI: 33.0-70.8%) in plasma samples collected prior to and within 48 h of antifungal therapy respectively. The diagnostic specificity was 100% (20/20, 95% CI: 83.9-100%). This assay provides a useful tool for the rapid diagnosis of T. marneffei infection and has the potential to improve the management of patients with penicilliosis.

Thao VP, Quang VM, Day JN, Chinh NT, Shikuma CM, Farrar J, Van Vinh Chau N, Thwaites GE, Dunstan SJ, Le T. 2016. High prevalence of PI resistance in patients failing second-line ART in Vietnam. J Antimicrob Chemother, 71 (3), pp. 762-774. | Show Abstract | Read more

BACKGROUND: There are limited data from resource-limited settings on antiretroviral resistance mutations that develop in patients failing second-line PI ART. METHODS: We performed a cross-sectional virological assessment of adults on second-line ART for ≥6 months between November 2006 and December 2011, followed by a prospective follow-up over 2 years of patients with virological failure (VF) at the Hospital for Tropical Diseases, Vietnam. VF was defined as HIV RNA concentrations ≥1000 copies/mL. Resistance mutations were identified by population sequencing of the pol gene and interpreted using the 2014 IAS-USA mutation list and the Stanford algorithm. Logistic regression modelling was performed to identify predictors of VF. RESULTS: Two hundred and thirty-one patients were enrolled in the study. The median age was 32 years; 81.0% were male, 95.7% were on a lopinavir/ritonavir-containing regimen and 22 (9.5%) patients had VF. Of the patients with VF, 14 (64%) carried at least one major protease mutation [median: 2 (IQR: 1-3)]; 13 (59%) had multiple protease mutations conferring intermediate- to high-level resistance to lopinavir/ritonavir. Mutations conferring cross-resistance to etravirine, rilpivirine, tipranavir and darunavir were identified in 55%, 55%, 45% and 27% of patients, respectively. Higher viral load, adherence <95% and previous indinavir use were independent predictors of VF. The 2 year outcomes of the patients maintained on lopinavir/ritonavir included: death, 7 (35%); worsening virological/immunological control, 6 (30%); and virological re-suppression, 5 (25%). Two patients were switched to raltegravir and darunavir/ritonavir with good HIV control. CONCLUSIONS: High-prevalence PI resistance was associated with previous indinavir exposure. Darunavir plus an integrase inhibitor and lamivudine might be a promising third-line regimen in Vietnam.

Le T, Cash-Goldwasser S, Tho PV, Lan NPH, Campbell JI, van Doorn HR, Lam NT, Trung NV, Trinh DT, Van Kinh N, Wertheim HFL. 2015. Diagnosing Rhodococcus equi infections in a setting where tuberculosis is highly endemic: a double challenge. J Clin Microbiol, 53 (4), pp. 1431-1433. | Show Abstract | Read more

Rhodococcus equi infection is increasing in regions with high HIV prevalence worldwide. The microbiological features and clinical mimicry of tuberculosis infection pose diagnostic challenges in high-tuberculosis-incidence settings. We present two HIV-associated cases of R. equi infection from Vietnam and discuss the unique diagnostic challenges in such settings.

Bulterys PL, Le T, Quang VM, Nelson KE, Lloyd-Smith JO. 2013. Environmental predictors and incubation period of AIDS-associated penicillium marneffei infection in Ho Chi Minh City, Vietnam. Clin Infect Dis, 56 (9), pp. 1273-1279. | Show Abstract | Read more

BACKGROUND: Penicillium marneffei is an emerging dimorphic mycosis endemic in Southeast Asia, and a leading cause of mortality among human immunodeficiency virus (HIV)-infected people in the region. Factors governing the seasonal incidence of P. marneffei infection are unknown, and may yield critical insights into possible reservoirs or modes of acquisition. METHODS: This study included HIV-infected patients presenting with P. marneffei (n = 719) and Cryptococcus neoformans (n = 1598) infection to the Hospital for Tropical Diseases in Ho Chi Minh City, Vietnam, from 2004 to 2010, and temperature, humidity, wind, precipitation, and HIV-related admissions data for the corresponding period. We used multivariate regression modeling to identify factors associated with P. marneffei and C. neoformans admissions. We estimated the P. marneffei incubation period by considering profile likelihoods for different exposure-to-admission delays. RESULTS: We found that P. marneffei admissions were strongly associated with humidity (P < .001), and that precipitation, temperature, and wind did not add explanatory power. Cryptococcus neoformans admissions were not seasonal, and P. marneffei admissions were more common relative to C. neoformans admissions during months of high (≥85%) humidity (odds ratio, 1.49; 95% confidence interval [CI], 1.10-2.01). Maximum likelihood estimation suggested a P. marneffei incubation period of 1 week (95% CI, 0-3 weeks). CONCLUSIONS: Our findings suggest that humidity is the most important environmental predictor of P. marneffei admissions, and may drive exposure by facilitating fungal growth or spore release in the environment. In addition, it appears that a high proportion of penicilliosis patients present to the hospital with primary disseminated infection within 3 weeks of exposure.

Larsson M, Nguyen LHT, Wertheim HF, Dao TT, Taylor W, Horby P, Nguyen TV, Nguyen MHT, Le T, Nguyen KV. 2012. Clinical characteristics and outcome of Penicillium marneffei infection among HIV-infected patients in northern Vietnam. AIDS Res Ther, 9 (1), pp. 24. | Show Abstract | Read more

OBJECTIVE: This study reports the clinical characteristics and outcome of HIV-associated Penicilliummarneffei infection in northern Vietnam. METHODS: We conducted a retrospective chart review of all patients with laboratory confirmed Penicilliummarneffei infection admitted to the National Hospital for Tropical Diseases in Hanoi, Vietnam, between July 2006 and September 2009. RESULTS: 127 patients with P. marneffei infection were identified. All were HIV-infected; median CD4+ T-cell count was 24 cells/μl (IQR:12-48); 76% were men. Common clinical features were fever (92.9%), skin lesions (82.6%), hepatomegaly (61.4%), lymphadenopathy (40.2%), weight loss (59.1%) and cough (49.6%). Concurrent opportunistic infections were present in 22.0%; half of those had tuberculosis. Initial treatment regimens were: itraconazole or ketoconazole capsule (77.2%), amphotericin B (20.5%), and fluconazole (1.6%). In-hospital mortality was 12.6% and showed no significant difference in patients treated with itraconazole (or ketoconazole) and amphotericin B (p = 0.43). Dyspnea, ascites, and increased LDH level were independent predictors of mortality. No seasonality was observed. CONCLUSION: The clinical features, treatments and outcomes of HIV-associated P. marneffei infection in northern Vietnam are similar to those reported in other endemic regions. Dyspnea was an important predictor of mortality. More patients were treated with itraconazole than amphotericin B and no significant difference in treatment outcome was observed. It would be of clinical value to compare the efficacy of oral itraconazole and amphotericin B in a clinical trial.

Thao VP, Le T, Török EM, Yen NTB, Chau TTH, Jurriaans S, van Doorn HR, de Jong MD, Farrar JJ, Dunstan SJ. 2012. HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam. Antivir Ther, 17 (5), pp. 905-913. | Show Abstract | Read more

BACKGROUND: Access to antiretroviral therapy (ART) for HIV-infected individuals in Vietnam is rapidly expanding, but there are limited data on HIV drug resistance (HIVDR) to guide ART strategies. METHODS: We retrospectively conducted HIVDR testing in 220 ART-naive individuals recruited to a randomized controlled trial of immediate versus deferred ART in individuals with HIV-associated tuberculous meningitis in Ho Chi Minh City (HCMC) from 2005-2008. HIVDR mutations were identified by population sequencing of the HIV pol gene and were defined based on 2009 WHO surveillance drug resistance mutations (SDRMs). RESULTS: We successfully sequenced 219/220 plasma samples of subjects prior to ART; 218 were subtype CRF01_AE and 1 was subtype B. SDRMs were identified in 14/219 (6.4%) subjects; 8/14 were resistant to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs; T69D, L74V, V75M, M184V/I and K219R), 5/14 to non-nucleoside reverse transcriptase inhibitors (NNRTIs; K103N, V106M, Y181C, Y188C and G190A), 1/14 to both NRTIs and NNRTIs (D67N and Y181C) and none to protease inhibitors. After 6 months of ART, eight subjects developed protocol-defined virological failure. HIVDR mutations were identified in 5/8 subjects. All five had mutations with high-level resistance to NNRTIs and three had mutations with high-level resistance to NRTIs. Due to a high early mortality rate (58%), the effect of pre-existing HIVDR mutations on treatment outcome could not be accurately assessed. CONCLUSIONS: The prevalence of WHO SDRMs in ART-naive individuals with HIV-associated tuberculous meningitis in HCMC from 2005-2008 is 6.4%. The SDRMs identified conferred resistance to NRTIs and/or NNRTIs, reflecting the standard first-line ART regimens in Vietnam.

Thao VP, Le T, Toeroek EM, Yen NTB, Chau TTH, Jurriaans S, van Doorn HR, de Jong MD, Farrar JJ, Dunstan SJ. 2012. HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam (vol 17, pg 905, 2012) ANTIVIRAL THERAPY, 17 (5), pp. 937-937. | Read more

Nga TVT, Parry CM, Le T, Lan NPH, Diep TS, Campbell JI, Hoang NVM, Dung LT, Wain J, Dolecek C et al. 2012. The decline of typhoid and the rise of non-typhoid salmonellae and fungal infections in a changing HIV landscape: bloodstream infection trends over 15 years in southern Vietnam. Trans R Soc Trop Med Hyg, 106 (1), pp. 26-34. | Show Abstract | Read more

The etiological spectrum of bloodstream infections is variable between industrialized and developing countries and even within a defined location over time. We investigated trends in bloodstream infections at an infectious disease hospital in Ho Chi Minh City, Vietnam, from 1994-2008. Amongst 66,111 blood cultures performed, a clinically relevant pathogen was isolated in 7645 episodes (positivity rate; 116/1000 cultures). Salmonella Typhi was the predominant pathogen until 2002; however, a considerable annual decline in the proportion of S. Typhi was observed (OR 0.6993, 95% CI [0.6885, 0.7103], p<0.0001). Conversely, there was a significant increase in the proportions of non-typhoidal Salmonella (NTS), Cryptococcus neoformans and Penicillium marneffei, concurrent with increasing HIV prevalence. These data document a substantial longitudinal shift in bloodstream infection etiology in southern Vietnam. We propose such changes are related to increasing economic prosperity and HIV prevalence, and this pattern marks a substantial change in the epidemiology of invasive salmonellosis in Southeast Asia.

Le T, Wolbers M, Chi NH, Quang VM, Chinh NT, Lan NPH, Lam PS, Kozal MJ, Shikuma CM, Day JN, Farrar J. 2011. Epidemiology, seasonality, and predictors of outcome of AIDS-associated Penicillium marneffei infection in Ho Chi Minh City, Viet Nam. Clin Infect Dis, 52 (7), pp. 945-952. | Show Abstract | Read more

BACKGROUND: Penicillium marneffei is an important human immunodeficiency virus (HIV)-associated opportunistic pathogen in Southeast Asia. The epidemiology and the predictors of penicilliosis outcome are poorly understood. METHODS: We performed a retrospective study of culture-confirmed incident penicilliosis admissions during 1996-2009 at the Hospital for Tropical Diseases in Ho Chi Minh City, Viet Nam. Seasonality of penicilliosis was assessed using cosinor models. Logistic regression was used to assess predictors of death or worsening disease based on 10 predefined covariates, and Cox regression was performed to model time-to-antifungal initiation. RESULTS: A total of 795 patients were identified; hospital charts were obtainable for 513 patients (65%). Cases increased exponentially and peaked in 2007 (156 cases), mirroring the trends in AIDS admissions during the study period. A highly significant seasonality for penicilliosis (P<.001) but not for cryptococcosis (P=.63) or AIDS admissions (P=.83) was observed, with a 27% (95% confidence interval, 14%-41%) increase in incidence during rainy months. All patients were HIV infected; the median CD4 cell count (62 patients) was 7 cells/μL (interquartile range, 4-24 cells/μL). Hospital outcome was an improvement in 347 (68%), death in 101 (20%), worsening in 42 (8%), and nonassessable in 23 (5%) cases. Injection drug use, shorter history, absence of fever or skin lesions, elevated respiratory rates, higher lymphocyte count, and lower platelet count independently predicted poor outcome in both complete-case and multiple-imputation analyses. Time-to-treatment initiation was shorter for patients with skin lesions (hazard ratio, 3.78; 95% confidence interval, 2.96-4.84; P<.001). CONCLUSIONS: Penicilliosis incidence correlates with the HIV/AIDS epidemic in Viet nam. The number of cases increases during rainy months. Injection drug use, shorter history, absence of fever or skin lesions, respiratory difficulty, higher lymphocyte count, and lower platelet count predict poor in-hospital outcome.

Le T, Farrar J, Shikuma C. 2011. Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication. AIDS, 25 (6), pp. 871-872. | Read more

Le T, Huu Chi N, Kim Cuc NT, Manh Sieu TP, Shikuma CM, Farrar J, Day JN. 2010. AIDS-associated Penicillium marneffei infection of the central nervous system. Clin Infect Dis, 51 (12), pp. 1458-1462. | Show Abstract | Read more

Penicillium marneffei is an important human immunodeficiency virus-associated opportunistic infection endemic in Southeast Asia. Central nervous system infection has not been described. We report the first case series of 21 human immunodeficiency virus-infected patients who presented with a syndrome consistent with acute central nervous system infection and who had Penicillium marneffei isolated from cerebrospinal fluid.

Le T, Hong Chau TT, Kim Cuc NT, Si Lam P, Manh Sieu TP, Shikuma CM, Day JN. 2010. AIDS‐associated Cryptococcus neoformans and Penicillium marneffei coinfection: a therapeutic dilemma in resource‐limited settings. Clin Infect Dis, 51 (9), pp. e65-e68. | Show Abstract | Read more

AIDS&#x2010;associated Cryptococcus neoformans and Penicillium marneffei coinfection has not been adequately studied and poses unique therapeutic challenges in resource&#x2010;limited settings. Itraconazole poorly penetrates the central nervous system, whereas fluconazole has poor activity against P. marneffei. We prospectively report management of 1 patient and retrospectively review 7 coinfection cases from Vietnam.

Le V, Le T, Cao T, Le L, Tran N, Le TP, Nguyen H, Campbell J, Baker S, Farrar J, Schultsz C. 2008. Prevalence of qnr and aac(6 ')-Ib-cr Genes in Community-Acquired Enterobacteriaceae Isolated in Healthy Volunteers in Hochiminh City INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 12 pp. E117-E118. | Read more

Thao VP, Le T, Török EM, Yen NTB, Chau TTH, Jurriaans S, van Doorn HR, de Jong MD, Farrar JJ, Dunstan SJ. 2012. HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam. Antivir Ther, 17 (5), pp. 905-913. | Show Abstract | Read more

BACKGROUND: Access to antiretroviral therapy (ART) for HIV-infected individuals in Vietnam is rapidly expanding, but there are limited data on HIV drug resistance (HIVDR) to guide ART strategies. METHODS: We retrospectively conducted HIVDR testing in 220 ART-naive individuals recruited to a randomized controlled trial of immediate versus deferred ART in individuals with HIV-associated tuberculous meningitis in Ho Chi Minh City (HCMC) from 2005-2008. HIVDR mutations were identified by population sequencing of the HIV pol gene and were defined based on 2009 WHO surveillance drug resistance mutations (SDRMs). RESULTS: We successfully sequenced 219/220 plasma samples of subjects prior to ART; 218 were subtype CRF01_AE and 1 was subtype B. SDRMs were identified in 14/219 (6.4%) subjects; 8/14 were resistant to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs; T69D, L74V, V75M, M184V/I and K219R), 5/14 to non-nucleoside reverse transcriptase inhibitors (NNRTIs; K103N, V106M, Y181C, Y188C and G190A), 1/14 to both NRTIs and NNRTIs (D67N and Y181C) and none to protease inhibitors. After 6 months of ART, eight subjects developed protocol-defined virological failure. HIVDR mutations were identified in 5/8 subjects. All five had mutations with high-level resistance to NNRTIs and three had mutations with high-level resistance to NRTIs. Due to a high early mortality rate (58%), the effect of pre-existing HIVDR mutations on treatment outcome could not be accurately assessed. CONCLUSIONS: The prevalence of WHO SDRMs in ART-naive individuals with HIV-associated tuberculous meningitis in HCMC from 2005-2008 is 6.4%. The SDRMs identified conferred resistance to NRTIs and/or NNRTIs, reflecting the standard first-line ART regimens in Vietnam.

Le T, Wolbers M, Chi NH, Quang VM, Chinh NT, Lan NPH, Lam PS, Kozal MJ, Shikuma CM, Day JN, Farrar J. 2011. Epidemiology, seasonality, and predictors of outcome of AIDS-associated Penicillium marneffei infection in Ho Chi Minh City, Viet Nam. Clin Infect Dis, 52 (7), pp. 945-952. | Show Abstract | Read more

BACKGROUND: Penicillium marneffei is an important human immunodeficiency virus (HIV)-associated opportunistic pathogen in Southeast Asia. The epidemiology and the predictors of penicilliosis outcome are poorly understood. METHODS: We performed a retrospective study of culture-confirmed incident penicilliosis admissions during 1996-2009 at the Hospital for Tropical Diseases in Ho Chi Minh City, Viet Nam. Seasonality of penicilliosis was assessed using cosinor models. Logistic regression was used to assess predictors of death or worsening disease based on 10 predefined covariates, and Cox regression was performed to model time-to-antifungal initiation. RESULTS: A total of 795 patients were identified; hospital charts were obtainable for 513 patients (65%). Cases increased exponentially and peaked in 2007 (156 cases), mirroring the trends in AIDS admissions during the study period. A highly significant seasonality for penicilliosis (P<.001) but not for cryptococcosis (P=.63) or AIDS admissions (P=.83) was observed, with a 27% (95% confidence interval, 14%-41%) increase in incidence during rainy months. All patients were HIV infected; the median CD4 cell count (62 patients) was 7 cells/μL (interquartile range, 4-24 cells/μL). Hospital outcome was an improvement in 347 (68%), death in 101 (20%), worsening in 42 (8%), and nonassessable in 23 (5%) cases. Injection drug use, shorter history, absence of fever or skin lesions, elevated respiratory rates, higher lymphocyte count, and lower platelet count independently predicted poor outcome in both complete-case and multiple-imputation analyses. Time-to-treatment initiation was shorter for patients with skin lesions (hazard ratio, 3.78; 95% confidence interval, 2.96-4.84; P<.001). CONCLUSIONS: Penicilliosis incidence correlates with the HIV/AIDS epidemic in Viet nam. The number of cases increases during rainy months. Injection drug use, shorter history, absence of fever or skin lesions, respiratory difficulty, higher lymphocyte count, and lower platelet count predict poor in-hospital outcome.

Le T, Huu Chi N, Kim Cuc NT, Manh Sieu TP, Shikuma CM, Farrar J, Day JN. 2010. AIDS-associated Penicillium marneffei infection of the central nervous system. Clin Infect Dis, 51 (12), pp. 1458-1462. | Show Abstract | Read more

Penicillium marneffei is an important human immunodeficiency virus-associated opportunistic infection endemic in Southeast Asia. Central nervous system infection has not been described. We report the first case series of 21 human immunodeficiency virus-infected patients who presented with a syndrome consistent with acute central nervous system infection and who had Penicillium marneffei isolated from cerebrospinal fluid.

Le T, Hong Chau TT, Kim Cuc NT, Si Lam P, Manh Sieu TP, Shikuma CM, Day JN. 2010. AIDS‐associated Cryptococcus neoformans and Penicillium marneffei coinfection: a therapeutic dilemma in resource‐limited settings. Clin Infect Dis, 51 (9), pp. e65-e68. | Show Abstract | Read more

AIDS&#x2010;associated Cryptococcus neoformans and Penicillium marneffei coinfection has not been adequately studied and poses unique therapeutic challenges in resource&#x2010;limited settings. Itraconazole poorly penetrates the central nervous system, whereas fluconazole has poor activity against P. marneffei. We prospectively report management of 1 patient and retrospectively review 7 coinfection cases from Vietnam.

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