Association between HIV genotype, viral load and disease progression in a cohort of Thai men who have sex with men with estimated dates of HIV infection

<div><p>Background</p><p>Differences between HIV genotypes may affect HIV disease progression. We examined infecting HIV genotypes and their association with disease progression in a cohort of men who have sex with men with incident HIV infection in Bangkok, Thailand.</p><p>Methods</p><p>We characterized the viral genotype of 189 new HIV infections among MSM identified between 2006–2014 using hybridization and sequencing. Plasma viral load (PVL) was determined by PCR, and CD4+ T-cell counts were measured by flow cytometry. We used Generalized Estimating Equations to examine factors associated with changes in CD4+ T-cell counts. Factors associated with immunologic failure were analyzed using Cox proportional hazard models.</p><p>Results</p><p>Among 189 MSM, 84% were infected with CRF01_AE, 11% with recombinant B/CRF01_AE and 5% with subtype B. CD4+ T-cell decline rates were 68, 65, and 46 cells/μL/year for CRF01_AE, recombinants, and subtype B, respectively, and were not significantly different between HIV subtypes. CD4+ T-cell decline rate was significantly associated with baseline PVL and CD4+ T-cell counts (p <0.001). Progression to immunologic failure was associated with baseline CD4+ T-cell ≤ 500 cells/μL (AHR 1.97; 95% CI 1.14–3.40, p = 0.015) and PVL > 50,000 copies/ml (AHR 2.03; 1.14–3.63, p = 0.017). There was no difference in time to immunologic failure between HIV subtypes.</p><p>Conclusion</p><p>Among HIV-infected Thai MSM, low baseline CD4+ T-cell and high PVL are associated with rapid progression. In this cohort, no significant difference in CD4+ T-cell decline rate or time to immunologic failure was seen between CRF01_AE and other infecting HIV subtypes.</p></div

Baseline characteristics of MSM infected with HIV-1 subtype B, CRF01_AE and recombinant B/CRF01_AE, Bangkok Men Who Have Sex with Men Cohort Study, Bangkok, Thailand, 2006–2014.

<p>Baseline characteristics of MSM infected with HIV-1 subtype B, CRF01_AE and recombinant B/CRF01_AE, Bangkok Men Who Have Sex with Men Cohort Study, Bangkok, Thailand, 2006–2014.</p

Hazard ratios (HRs) for clinical progression from estimate date of infection (EDI) to immunologic failure.

<p>Hazard ratios (HRs) for clinical progression from estimate date of infection (EDI) to immunologic failure.</p

Kaplan-Meier survival curves.

<p>(A) Time to immunologic failure by infecting HIV subtype; (B) Time to immunologic failure by age at HIV conversion; (C) Time to immunologic failure by baseline CD4+ cell counts; (D) Time to immunologic failure by baseline viral load.</p

Utility of Cryptococcal Antigen Screening and Evolution of Asymptomatic Cryptococcal Antigenemia among HIV-Infected Women Starting Antiretroviral Therapy in Thailand

Cryptococcal meningitis (CM) remains a significant HIV-associated opportunistic infection in Southeast Asia and Africa, with a high burden of disease and a high mortality rate despite the availability of antiretroviral therapy (ART). We retrospectively examined the utility of cryptococcal antigen screening to identify risk for CM among 211 Thai women initiating ART. Antigenemia prevalence was 11% (n = 9) among 84 women with a CD4 count <100 cells/mm 3 . Screening identified all women who later developed CM. Cryptococcal antigen titers decreased over time with ART. Our study confirmed findings from previous studies in Thailand and South Africa and provided novel observational data regarding the course of cryptococcal antigenemia in patients initiating ART and the poor efficacy of low-dose fluconazole prophylaxis in preventing CM among patients with antigenemia

Assessment of Oral Fluid HIV Test Performance in an HIV Pre-Exposure Prophylaxis Trial in Bangkok, Thailand.

Rapid easy-to-use HIV tests offer opportunities to increase HIV testing among populations at risk of infection. We used the OraQuick Rapid HIV-1/2 antibody test (OraQuick) in the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial among people who inject drugs.The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. We tested participants' oral fluid for HIV using OraQuick monthly and blood using a nucleic-acid amplification test (NAAT) every 3 months. We used Kaplan-Meier methods to estimate the duration from a positive HIV NAAT until the mid-point between the last non-reactive and first reactive oral fluid test and proportional hazards to examine factors associated with the time until the test was reactive.We screened 3678 people for HIV using OraQuick. Among 447 with reactive results, 436 (97.5%) were confirmed HIV-infected, 10 (2.2%) HIV-uninfected, and one (0.2%) had indeterminate results. Two participants with non-reactive OraQuick results were, in fact, HIV-infected at screening yielding 99.5% sensitivity, 99.7% specificity, a 97.8% positive predictive value, and a 99.9% negative predictive value. Participants receiving tenofovir took longer to develop a reactive OraQuick (191.8 days) than participants receiving placebo (16.8 days) (p = 0.02) and participants infected with HIV CRF01_AE developed a reactive OraQuick earlier than participants infected with other subtypes (p = 0.04).The oral fluid HIV test performed well at screening, suggesting it can be used when rapid results and non-invasive tools are preferred. However, participants receiving tenofovir took longer to develop a reactive oral fluid test result than those receiving placebo. Thus, among people using pre-exposure prophylaxis, a blood-based HIV test may be an appropriate choice.ClinicalTrials.gov NCT00119106

Kaplan-Meier estimates of time (28 day months) from date HIV was detected using nucleic acid amplification until the mid-point date between the last non-reactive and first reactive oral fluid HIV test.

<p>(A) By study drug group: tenofovir or placebo. (B) Controlling for study drug group, by HIV subtype: CRF01_AE or other subtypes.</p

HIV test results of participants in the Bangkok Tenofovir Study, 2005–2012.

<p>OraQuick, OraQuick Rapid HIV-1/2 Antibody Test; EIA, enzyme immune assay; NAAT, nucleic-acid amplification test. ^aTwo participants with reactive OraQuick tests during follow-up were later found to have been HIV-infected before enrollment. ^bPlasma collected at 3-monthly visits from participants with a non-reactive OraQuick test result was tested for HIV using EIA.</p