Wanna Leelawiwat

Suppressive acyclovir therapy reduces HIV cervicovaginal shedding in HIV- and HSV-2-infected women, Chiang Rai, Thailand.

Background:Herpes simplex virus type 2 infection is important in the HIV epidemic and may contribute to increased HIV transmission. We evaluated the effect of suppressive acyclovir therapy on cervicovaginal HIV-1 shedding. Methods:HIV-1- and herpes simplex virus type 2-coinfected women aged 18-49 years with CD4 counts >200 cells/μL were enrolled in a randomized crossover trial of suppressive acyclovir therapy (NCT00362596, http://www.clinicaltrials.gov). For each woman, monthly plasma and weekly cervicovaginal lavage specimens were collected; the mean of the monthly median cervicovaginal lavage HIV-1 viral load and plasma HIV-1 viral load was compared. Results:Sixty-seven women were enrolled; at baseline, median CD4 count was 366 cells/μL, and median HIV-1 plasma viral load was 4.6 log10 copies/mL. The mean cervicovaginal lavage HIV-1 viral load was 1.9 (SD 0.8) log10 copies/mL during the acyclovir month and 2.2 (SD 0.7) log10 copies/mL during the placebo month (P < 0.0001); the mean decrease in HIV was 0.3 log10 copies/mL. The mean plasma HIV viral load during the acyclovir month (3.78 log10 copies/mL) was reduced compared with the placebo month (4.26 log10 copies/mL, P < 0.001). Conclusions:Acyclovir reduced HIV genital shedding and plasma viral load among HIV-1- and herpes simplex virus type 2-coinfected women. Further data from clinical trials will examine the effect of suppressive therapy on HIV transmission.

Maternal herpes simplex virus type 2 coinfection increases the risk of perinatal HIV transmission : possibility to further decrease transmission?

Objectives:To evaluate the association between maternal herpes simplex virus type 2 seropositivity and genital herpes simplex virus type 2 shedding with perinatal HIV transmission. Study design:Evaluation of women who participated in a 1996–1997 perinatal HIV transmission prevention trial in Thailand. Methods:In this nonbreastfeeding population, women were randomized to zidovudine or placebo from 36 weeks gestation through delivery; maternal plasma and cervicovaginal HIV viral load and infant HIV status were determined for the original study. Stored maternal plasma and cervicovaginal samples were tested for herpes simplex virus type 2 antibodies by enzyme-linked immunoassay and for herpes simplex virus type 2 DNA by real-time PCR, respectively. Results:Among 307 HIV-positive women with available samples, 228 (74.3%) were herpes simplex virus type 2 seropositive and 24 (7.8%) were shedding herpes simplex virus type 2. Herpes simplex virus type 2 seropositivity was associated with overall perinatal HIV transmission [adjusted odds ratio, 2.6; 95% confidence interval, 1.0–6.7)], and herpes simplex virus type 2 shedding was associated with intrapartum transmission (adjusted odds ratio, 2.9; 95% confidence interval, 1.0–8.5) independent of plasma and cervicovaginal HIV viral load, and zidovudine treatment. Median plasma HIV viral load was higher among herpes simplex virus type 2 shedders (4.2 vs. 4.1 log10copies/ml; P = 0.05), and more shedders had quantifiable levels of HIV in cervicovaginal samples, compared with women not shedding herpes simplex virus type 2 (62.5 vs. 34.3%; P = 0.005). Conclusion:We found an increased risk of perinatal HIV transmission among herpes simplex virus type 2 seropositive women and an increased risk of intrapartum HIV transmission among women shedding herpes simplex virus type 2. These novel findings suggest that interventions to control herpes simplex virus type 2 infection could further reduce perinatal HIV transmission.

Renal Function of Participants in the Bangkok Tenofovir Study—Thailand, 2005–2012

BACKGROUND Tenofovir disoproxil fumarate (tenofovir) has been associated with renal dysfunction in people infected with human immunodeficiency virus (HIV) receiving combination antiretroviral therapy. We reviewed data from an HIV preexposure prophylaxis trial to determine if tenofovir use was associated with changes in renal function in an HIV-uninfected population. METHODS During the trial, 2413 HIV-uninfected people who inject drugs were randomized to receive tenofovir or placebo. We assessed the renal function of trial participants with the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using t tests for cross-sectional analysis and linear regression for longitudinal analysis. RESULTS Creatinine clearance and glomerular filtration rate (GFR) results were lower at 24, 36, 48, and 60 months in the tenofovir group compared with the placebo group. Results declined more in the tenofovir group than in the placebo group during follow-up using the Cockcroft-Gault (P < .001) and CKD-EPI (P = .007) equations, but not MDRD (P = .12). Creatinine clearance measured when study drug was stopped was lower in the tenofovir group than the placebo group (P < .001), but the difference resolved when tested a median of 20 months later (P = .12). CONCLUSIONS We found small but significant decreases in cross-sectional measures of creatinine clearance and GFR in the tenofovir group compared with the placebo group and modest differences in downward trends in longitudinal analysis using the Cockcroft-Gault and CKD-EPI equations. These results suggest that with baseline assessments of renal function and routine monitoring of creatinine clearance during follow-up, tenofovir can be used safely for HIV preexposure prophylaxis. Clinical Trials Registration. NCT00119106.

Increase in sexual risk behavior and prevalence of Chlamydia trachomatis among adolescents in Northern Thailand.

Background: Monitoring changes in adolescent sexual risk behaviors and sexually transmitted infections is critical for evaluating the effectiveness of human immunodeficiency virus and other prevention programs, but population-based data on adolescents in Thailand are limited. We report findings from 2 cross-sectional surveys conducted in 1999 and 2002 among 15-to 21-year-old vocational students. Methods: In 1999 and 2002, 1725 and 966 students, respectively, were interviewed using computer-assisted self-interview methods. Urine samples were collected and tested for Chlamydia trachomatis and Neisseria gonorrhoeae by polymerase chain reaction. Results: From 1999 to 2002 C. trachomatis prevalence increased from 3.2% to 7.5% (P <0.001) in women and from 2.5% to 6.0% (P <0.001) in men. There was an increase in the reported mean lifetime number of steady sexual partners among both men (3.4–4.7, P = 0.01) and women (2.5–3.3, P <0.001), and in the mean lifetime number of casual partners among men (1.1–2.1, P <0.001) and women (0.3–1.1, P = 0.04). Reported consistent condom use decreased significantly among women with casual partners (43%–19%, P = 0.03) but not among men (25%–31%, P = 0.31). Conclusions: Our study identified important increases in the prevalence of chlamydial infection and in sexual risk behaviors among Thai adolescents over a 3-year period. These findings are consistent with other studies suggesting profound social changes are changing norms of adolescent sexual behavior in Thailand, and highlight the need for adolescent sexual health services and prevention programming.

Cyclic changes in HIV shedding from the female genital tract during the menstrual cycle

Factors increasing genital human immunodeficiency virus (HIV) shedding may increase female-to-male HIV transmission risk. We examined HIV shedding in 67 women with HIV type 1 and herpes simplex virus type 2 coinfection, during 2 menstrual cycles. Shedding occurred in 60%, 48%, and 54% of samples during the follicular, periovulatory, and luteal phases, respectively (P = .01). Shedding declined after menses until ovulation, with a slope -0.054 log10 copies/swab/day (P < .001), corresponding to a change of approximately 0.74 log10 copies between peak and nadir levels. Shedding increased during the luteal phase only among women with CD4 counts of <350 cells/µL. In reproductive-aged women, shedding frequency and magnitude are greatest immediately following menses and lowest at ovulation.

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

Background 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. Methods 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. Results 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). Discussion 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. Trial Registration ClinicalTrials.gov NCT00119106.

Analysis of False-Negative Human Immunodeficiency Virus Rapid Tests Performed on Oral Fluid in 3 International Clinical Research Studies

Background. The OraQuick Advance Rapid HIV-1/2 Test is a point-of-care test capable of detecting human immunodeficiency virus (HIV)-specific antibodies in blood and oral fluid. To understand test performance and factors contributing to false-negative results in longitudinal studies, we examined results of participants enrolled in the Botswana TDF/FTC Oral HIV Prophylaxis Trial, the Bangkok Tenofovir Study, and the Bangkok MSM Cohort Study, 3 separate clinical studies of high-risk, HIV-negative persons conducted in Botswana and Thailand. Methods. In a retrospective observational analysis, we compared oral fluid OraQuick (OFOQ) results among participants becoming HIV infected to results obtained retrospectively using enzyme immunoassay and nucleic acid amplification tests on stored specimens. We categorized negative OFOQ results as true-negative or false-negative relative to nucleic acid amplification test and/or enzyme immunoassay, and determined the delay in OFOQ conversion relative to the estimated time of infection. We used log-binomial regression and generalized estimating equations to examine the association between false-negative results and participant, clinical, and testing-site factors. Results. Two-hundred thirty-three false-negative OFOQ results occurred in 80 of 287 seroconverting individuals. Estimated OFOQ conversion delay ranged from 14.5 to 547.5 (median, 98.5) days. Delayed OFOQ conversion was associated with clinical site and test operator (P < .05), preexposure prophylaxis (P = .01), low plasma viral load (P < .02), and time to kit expiration (P < .01). Participant age, sex, and HIV subtype were not associated with false-negative results. Long OFOQ conversion delay time was associated with antiretroviral exposure and low plasma viral load. Conclusions. Failure of OFOQ to detect HIV-1 infection was frequent and multifactorial in origin. In longitudinal trials, negative oral fluid results should be confirmed via testing of blood samples.

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

Background 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. Methods 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. Results 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. Conclusion 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.

Self-collected genital swabs compared with cervicovaginal lavage for measuring HIV-1 and HSV-2 and the effect of acyclovir on viral shedding.

HIV-1 and HSV-2 are frequent genital co-infections in women. To determine how self-collected genital swabs compare to provider-collected cervicovaginal lavage, paired self-collected genital swabs and cervicovaginal lavage from women co-infected with HIV-1 and HSV-2 were evaluated. Women were in an acyclovir clinical trial and their samples were tested for HIV-1 RNA (361 samples) and HSV-2 DNA (378 samples). Virus shedding, quantity and acyclovir effect were compared. HIV-1 and HSV-2 were more frequently detected in self-collected genital swabs: 74.5% of self-collected genital swabs and 63.6% of cervicovaginal lavage had detectable HIV-1 (p ≤ 0.001, Fisher’s exact test) and 29.7% of self-collected genital swabs and 19.3% of cervicovaginal lavage had detectable HSV-2 (p ≤ 0.001) in the placebo month. Cervicovaginal lavage and self-collected genital swabs virus levels were correlated (Spearman’s rho, 0.68 for HIV; 0.61 for HSV-2) and self-collected genital swabs levels were generally higher. In multivariate modeling, self-collected genital swabs and cervicovaginal lavage could equally detect the virus-suppressive effect of acyclovir: for HIV-1, proportional odds ratios were 0.42 and 0.47 and for HSV-2, they were 0.10 and 0.03 for self-collected genital swabs and cervicovaginal lavage, respectively. Self-collected genital swabs should be considered for detection and measurement of HIV-1 and HSV-2 in clinical trials and other studies as they are a sensitive method to detect virus and can be collected in the home with frequent sampling.