Wannee Chonwattana

Temporal trends in HIV-1 incidence and risk behaviours in men who have sex with men in Bangkok, Thailand, 2006-13: An observational study

BACKGROUND HIV-1 incidence in men who have sex with men (MSM) is often difficult to estimate. We therefore assessed temporal trends in HIV-1 incidence and behavioural risk factors in MSM in Bangkok, Thailand, from 2006 to 2013. METHODS In this observational study, we used data for clients attending the Silom Community Clinic for voluntary counselling and testing (VCT) services and from the Bangkok MSM Cohort Study (BMCS) to investigate trends in HIV incidence per 100 person-years per quarter in both cohorts. During VCT, basic demographic data were gathered at registration. However, no behavioural risk data were gathered. In the BMCS, we gathered demographic and behavioural data at baseline and at regular study visits using audio computer-assisted self-interviewing. Questions were included about potential risk factors such as drug use, sexual practices, and how often condoms were used. We also analysed behavioural risk factors in the BMCS cohort, using a restricted cubic spline function for time. FINDINGS From 2006 to 2013, 8176 MSM came for VCT; 1999 (24%) clients were initially seronegative and returned for another test. 235 (12%) individuals seroconverted. The overall HIV-1 incidence was 5.5 per 100 person-years (95% CI 4.8-6.3), with an increasing trend (adjusted p=0.02). In the BMCS, 1372 people were seronegative at baseline; 1259 (92%) had more than one follow-up test and 238 (17%) seroconverted. The overall HIV-1 incidence was 5.3 per 100 person-years (95% CI 4.7-6.1), with an increase and then a decline (inverted U-shaped curve, p=0.0001). Individuals aged 21 years and younger were at significantly higher risk of HIV infection than were those aged 30 years and older in the in the VCT (rate ratio 2.29, 95% CI 1.88-2.78, p<0.0001) and BMCS cohorts (1.99, 1.50-2.65, p<0.0001). Overall, drug use (p=0.03), drug use to enhance sex (p=0.0006), use of drugs for erectile dysfunction (p<0.0001), and 100% condom use (p<0.0001) increased over time, whereas the proportion of individuals reporting receptive anal intercourse decreased (p=0.004). INTERPRETATION With a sustained high HIV-1 incidence and increasing drug use in MSM in Bangkok, we urgently need innovative and acceptable HIV prevention interventions, especially for young MSM. FUNDING US Centers for Disease Control and Prevention.

UC781 Microbicide Gel Retains Anti-HIV Activity in Cervicovaginal Lavage Fluids Collected following Twice-Daily Vaginal Application

ABSTRACT The potent nonnucleoside reverse transcriptase inhibitor UC781 has been safety tested as a vaginal microbicide gel formulation for prevention of HIV-1 sexual transmission. To investigate whether UC781 retained anti-infective activity following exposure to the female genital tract, we conducted an ex vivo analysis of the UC781 levels and antiviral activity in cervicovaginal lavage (CVL) fluids from 25 Thai women enrolled in a 14-day safety trial of twice-daily vaginal application of two concentrations of the UC781 microbicide gel. CVL samples were collected from women in the 0.1% (n = 5), 0.25% (n = 15), and placebo (n = 5) gel arms following the first application of gel (T15 min) and 8 to 24 h after the final application (T8-24 h) and separated into cell-free (CVL-s) and pelletable (CVL-p) fractions. As UC781 is highly hydrophobic, there were significantly higher levels of UC781 in the CVL-p samples than in the CVL-s samples for the UC781 gel arms. In T8-24 h CVL-p samples, 2/5 and 13/15 samples collected from the 0.1% and 0.25% UC781 gel arms, respectively, efficiently blocked infection with ≥4 log10 50% tissue culture infective dose (TCID50) of a CCR5-tropic CRF01_AE HIV-1 virus stock. Independent of the arm, the 11 CVL-p samples with UC781 levels of ≥5 μg/CVL sample reduced infectious HIV by ≥4 log10 TCID50. Our results suggest that the levels and anti-infective activities of UC781 gel formulations are likely to be associated with a cellular or pelletable component in CVL samples. Therefore, cellular and pelletable fractions should be assayed for drug levels and anti-infective activity in preclinical studies of candidate microbicides.

Hepatitis A and hepatitis B infection prevalence and associated risk factors in men who have sex with men, Bangkok, 2006–2008

Despite the availability of safe and effective vaccines, little is known about prevalence and risk factors for hepatitis A (HAV) and hepatitis B virus (HBV) infection among Thai men who have sex with men. The prevalence of HAV and HBV infection among men who have sex with men cohort in Bangkok was assessed. Baseline blood specimens were drawn and demographic and behavioral data were collected. Bivariate and multivariate logistic regression analysis was used to analyze risk factors for prevalent HAV and HBV infection. One thousand two hundred ninety‐nine Thai men who have sex with men 18 years and older were enrolled. Among those with results, 349/1,291 (27.0%) had evidence of past or current hepatitis A infection. Of the 1,117 (86.5%) men with unambiguous HBV test results, 442 (39.6%) had serologic evidence of past/current infection, 103 (9.2%) were immune due to hepatitis B vaccination, 572 (51.2%) had no evidence of immunological exposure to HBV or vaccine. Of those with past/current HBV infection, 130 (29.4%) were HIV positive. Age >35 years was independently associated with both HAV and HBV infection. University education was protective against both HAV and HBV infection. Increased alcohol consumption, number of lifetime male sexual partners ≥10, and prevalent HIV infection were also independently associated with HBV infection. The prevalence of past/current HAV and HBV infection was high in Bangkok men who have sex with men. Age‐cohorts with a higher prevalence of hepatitis B vaccine induced immunity may be expected in the future. Hepatitis A and B vaccination is recommended. J. Med. Virol. 85:1499–1505, 2013.

Prevalence of Treponema pallidum seropositivity and herpes simplex virus type 2 infection in a cohort of men who have sex with men, Bangkok, Thailand, 2006–2010

We report prevalence of Treponema pallidum (TP) seropositivity and herpes simplex virus type 2 (HSV-2) infection and risk factors associated with their prevalence in a cohort of men who have sex with men (MSM) in Bangkok, Thailand. Between April 2006 and March 2010 we enrolled Thai MSM into a cohort study based at the Silom Community Clinic, with baseline behavioural data and laboratory testing for sexually transmitted infections (STIs). Logistic regression was used to analyse risk factors associated with the prevalence of TP seropositivity and HSV-2 infection. From a total of 1544 enrolled men (mean age 26 years) TP, HSV-2 and HIV seropositive rates were 4.4%, 20.7% and 21.6%, respectively. After multivariable analysis, participating in group sex, reporting paying for sex, reporting sex with a casual partner in a park and being HSV-2 seropositive were associated with TP prevalence. Age ≥30 years, having less than a high school education, past use of recreational drugs, meeting casual sexual partners at a public venue (sauna) and TP seropositivity were associated with HSV-2 infection. The significant baseline prevalence of TP seropositivity and HSV-2 infection in this cohort demonstrates the need for screening and treatment of these STIs and targeted prevention interventions in Thai MSM in Bangkok.

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.

Hepatitis B vaccination uptake and correlates of serologic response among HIV-infected and uninfected men who have sex with men (MSM) in Bangkok, Thailand.

BACKGROUND Vaccination against hepatitis B virus (HBV) is recommended for all HBV-susceptible men who have sex with men (MSM). There is limited information on correlates of immunity to HBV vaccination in this group. We present serologic response rates to hepatitis B vaccine and identify factors associated with impaired response among HIV-uninfected and HIV-infected Thai MSM. METHODOLOGY HBV-susceptible volunteers were offered hepatitis B vaccination at months zero, one, and six. We measured baseline (pre-vaccination) total serum IgG and IgG subclasses (all participants), baseline CD4 count, and plasma HIV-1 viral load (PVL) (HIV+ participants). HBV serologies were retested at 12 months. Serologic responses were compared between all groups in men receiving three vaccine doses. RESULTS 511/651 HIV-negative and 64/84 HIV-positive participants completed the three-dose series. Response rates in HIV-uninfected and -infected participants were 90.1% vs. 50.0% (p<0.0001). Median pre-vaccination IgG was higher among non-responders than responders overall (1238.9.0 vs. 1057.0mg/dL, p=0.003) and among HIV-infected participants (1534.0 vs. 1244.5mg/dL, p=0.005), but not significantly among HIV-uninfected participants (1105.5 vs. 1054.3mg/dL, p=0.96). Pre-vaccination IgG1 and IgG3 levels were higher among HIV-positive than HIV-negative participants (median 866.0 vs. 520.3, and 105.8 vs. 83.1mg/dL, respectively, p<0.0001). Among HIV-infected participants, median CD4 count in non-responders was 378 cells/μL vs. 431 cells/μL in responders (p=0.20). Median PVL in non-responders was 64,800 copies/mL vs. 15500 copies/mL in responders (p=0.04). Participants with pre-vaccination plasma IgG >1550 mg/dL and PVL >10,000 copies/mL were almost always non-responsive (p<0.01). CONCLUSIONS HIV infection was associated with poor vaccine responses. High plasma viral load, elevated pre-vaccination total serum IgG and elevated pre-vaccination IgG1 are associated with poorer response to vaccination among HIV-infected MSM. In this group, the combination of high PVL and pre-vaccination total IgG is highly predictive of vaccine failure.

Loss to follow-up and bias assessment among a cohort of Thai men who have sex with men in Bangkok, Thailand

Minimising loss to follow-up is essential to obtain unbiased results. This study aimed to assess factors associated with loss to follow-up and effects on biasing exposure-outcome associations in a cohort of men who have sex with men in Bangkok. We enrolled sexually-active Thai men who have sex with men, at least 18 years old, in a study with four-monthly follow-up visits. At each visit, men answered HIV risk behaviour questions using audio computer-assisted self-interview. Logistic regression was used to evaluate factors associated with loss to follow-up and bias between exposures and prevalent HIV infection were estimated using adjusted relative odds ratios. From 2006 to 2010, we enrolled 1744 men who have sex with men; as of April, 2014, 1256 (72%) had completed at least the month-36 visit; loss to follow-up was 9.6%. Factors independently associated with loss to follow-up were age (18–21 years), education (primary level or less, secondary or vocational education), living outside Bangkok and vicinity, sexual orientation (bisexual, heterosexual), previous HIV testing, HIV infection, and behaviour in the past 4 months (recreational drug use, reporting group sex). An effect of loss to follow-up on factors of prevalent HIV infection was found by sexual orientation (transgender) and unprotected anal intercourse (receptive/insertive). These findings highlight the need to strengthen post-HIV test counselling. Directed counselling for HIV care should be given to young men who have sex with men and recreational drug users.

Randomized Controlled Trial to Compare Immunogenicity of Standard-Dose Intramuscular Versus Intradermal Trivalent Inactivated Influenza Vaccine in HIV-Infected Men Who Have Sex With Men in Bangkok, Thailand

BACKGROUND Individuals infected with human immunodeficiency virus (HIV) are at increased risk for severe influenza, yet immune responses to standard-dose intramuscular (IM) influenza vaccine are suboptimal in this population. Intradermal (ID) delivery of influenza vaccine might improve immune response through enhanced stimulation of dendritic cells. METHODS We conducted a randomized, double-blind, controlled trial to compare the immunogenicity of off-label standard-dose (15 µg) ID vs standard-dose (15 µg) IM inactive influenza vaccine in HIV-infected men in Bangkok, Thailand. The primary study outcome was seroconversion (minimum titer of 1:40 and ≥4-fold rise in antibody titer) at 1 month postvaccination based on serum hemagglutination inhibition antibody titers against each vaccine strain. Adverse events (AEs) in the 7 days following vaccination were also assessed. RESULTS We enrolled 400 HIV-infected participants; 200 were randomly assigned to receive IM and 200 ID vaccine. Vaccine arms were well-balanced with respect to age, CD4 cell count, HIV RNA load, and antiretroviral treatment. Percentage of seroconversion to all (ID 14% vs IM 15%; P = .8) or at least 1 (ID 69% vs IM 68%; P = .7) of the 3 vaccine strains did not differ significantly between ID vs IM vaccine recipients. A higher proportion of participants who received ID vaccine had mild injection-site AEs compared with participants who received IM vaccine (77% vs 27%). CONCLUSIONS There were no significant differences in the immunogenicity of standard-dose ID vs IM influenza vaccine in this HIV-infected population in Thailand. Additional strategies to enhance immune responses to influenza vaccine among HIV-infected persons are needed. CLINICAL TRIALS REGISTRATION NCT01538940.

The finding of casual sex partners on the internet, methamphetamine use for sexual pleasure, and incidence of HIV infection among men who have sex with men in Bangkok, Thailand: an observational cohort study

BACKGROUND The finding of casual sex partners on the internet and methamphetamine use have been described as risk factors for HIV infection in men who have sex with men (MSM). However, the interplay between these factors has not been studied prospectively in one design. This study aims to determine the associations between finding casual sex partners on the internet and incident methamphetamine use and HIV infection. METHODS In this observational cohort study of Thai MSM, we recruited Bangkok residents aged 18 years or older with a history of penetrative male-to-male sex in the past 6 months. Baseline and follow-up visits were done at a dedicated study clinic in central Bangkok. Men were tested for HIV infection at every study visit and for sexually transmitted infections at baseline. Baseline demographics and HIV risk behaviour information were collected at every visit by audio computer-assisted self-interview. We used a descriptive model using bivariate odds ratios to elucidate the order of risk factors in the causal pathway to HIV incidence and methamphetamine use. We used Cox proportional hazard regression analysis to evaluate covariates for incident methamphetamine use and HIV infection. FINDINGS From April 6, 2006, to Dec 31, 2010, 1977 men were screened and 1764 were found eligible. 1744 men were enrolled, of whom 1372 tested negative for HIV and were followed up until March 20, 2012. Per 100 person-years of follow-up, incidence of methamphetamine use was 3·8 (128 events in 3371 person-years) and incidence of HIV infection was 6·0 (212 events in 3554 person-years). In our descriptive model, methamphetamine use, anal sex, and various other behaviours cluster together but their effect on HIV incidence was mediated by the occurrence of ulcerative sexually transmitted infections. Dual risk factors for both incident methamphetamine use and HIV infection were younger age and finding casual sex partners on the internet. Having ever received money for sex was predictive for incident methamphetamine use; living alone or with a housemate, recent anal sex, and ulcerative sexually transmitted infections at baseline were predictive for incident HIV infection. INTERPRETATION In MSM in Bangkok, casual sex partner recruitment on the internet, methamphetamine use, and sexually transmitted infections have important roles in sustaining the HIV epidemic. Virtual HIV prevention education, drug use harm reduction, and biomedical HIV prevention methods, such as pre-exposure prophylaxis, could help to reduce or revert the HIV epidemic among MSM in Bangkok. FUNDING US Centers for Disease Control and Prevention and the Johns Hopkins Fogarty AIDS International Training and Research Program.

Screening for Chlamydia trachomatis and Neisseria gonorrhoeae infection among asymptomatic men who have sex with men in Bangkok, Thailand:

We report positivity rates of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infection at each anatomic site among asymptomatic men who have sex with men (MSM). We calculated the number needed to screen (NNS) to detect CT and NG infection at each anatomic site. From 2006 to 2010, we enrolled Thai MSM, age ≥ 18 years into the Bangkok MSM Cohort Study. Participants underwent physical examination and had rectal, urethral, and pharyngeal screening for CT and NG infection using nucleic acid amplification tests (NAATs). Of 1744 enrollees, 1696 (97.2%) had no symptoms of CT and NG infection. The positivity rates of CT and NG infection at any site were 14.3% (rectum, urethra, pharynx) and 6.4% (rectum, urethra), respectively. The NNS to detect rectal CT and rectal NG infections was 10 and 16, respectively (p < 0.05). For urethral infection, the NNS of CT was lower than the NNS of NG (22, 121: p < 0.05). The lowest NNS found for rectal CT infection was in HIV-infected MSM (6, 5–8). Asymptomatic CT and NG infection were common among MSM in Bangkok, Thailand and frequently detected in the rectum. In setting where screening in all specimens using NAAT is not feasible, rectal screening should be a priority.