BACKGROUND: In response to the 2015-2016 Zika virus (ZIKV) outbreak and the causal relationship established between maternal ZIKV infection and adverse infant outcomes, we conducted a cohort study to estimate the incidence of ZIKV infection in pregnancy and assess its impacts in women and infants. METHODOLOGY/PRINCIPAL FINDINGS: From May 2018-January 2020, we prospectively followed pregnant women recruited from 134 participating hospitals in two non-adjacent provinces in northeastern Thailand. We collected demographic, clinical, and epidemiologic data and blood and urine at routine antenatal care visits until delivery. ZIKV infections were confirmed by real-time reverse transcriptase polymerase chain reaction (rRT-PCR). Specimens with confirmed ZIKV underwent whole genome sequencing. Among 3,312 women enrolled, 12 (0.36%) had ZIKV infections, of which two (17%) were detected at enrollment. Ten (83%, 3 in 2nd and 7 in 3rd trimester) ZIKV infections were detected during study follow-up, resulting in an infection rate of 0.15 per 1,000 person-weeks (95% CI: 0.07-0.28). The majority (11/12, 91.7%) of infections occurred in one province. Persistent ZIKV viremia (42 days) was found in only one woman. Six women with confirmed ZIKV infections were asymptomatic until delivery. Sequencing of 8 ZIKV isolates revealed all were of Asian lineage. All 12 ZIKV infected women gave birth to live, full-term infants; the only observed adverse birth outcome was low birth weight in one (8%) infant. Pregnancies in 3,300 ZIKV-rRT-PCR-negative women were complicated by 101 (3%) fetal deaths, of which 67 (66%) had miscarriages and 34 (34%) had stillbirths. There were no differences between adverse fetal or birth outcomes of live infants born to ZIKV-rRT-PCR-positive mothers compared to live infants born to ZIKV-rRT-PCR-negative mothers. CONCLUSIONS/SIGNIFICANCE: Confirmed ZIKV infections occurred infrequently in this large pregnancy cohort and observed adverse maternal and birth outcomes did not differ between mothers with and without confirmed infections.

PURPOSE: To examine how recent sex work is identified and the HIV risk factors and service needs among Thai cisgender men who have sex with men (MSM) and transgender women (TGW) who exchange sex. METHODS: MSM and TGW in Bangkok and Pattaya who exchanged sex in the last year (n= 890) were recruited through social media, outreach, and word-of-mouth. Recent sex exchange was based on the primary question, "in the last 30 days, have you sold or traded sex"; secondary questions (regarding income source and client encounters) were also investigated. RESULTS: Overall, 436 (48%) participants engaged in sex work in the last 30 days; among those, 270 (62%) reported exchanging sex by the primary question, and 160 (37%) based on secondary questions only. Recent sex exchange was associated with gonorrhea, syphilis, discussing PrEP with others, and using condoms, alcohol, methamphetamine, amyl nitrate, and Viagra®. Exchanging sex based on secondary questions only was associated with being in a relationship, social media recruitment, less recent anal intercourse, and not discussing PrEP. CONCLUSIONS: Thai MSM and TGW who exchange sex need regular access to HIV/STI prevention, testing, and treatment services, and multiple approaches to assessing sex work will help identify and serve this diverse and dynamic population.

To reach its goal of ending AIDS by 2030, Thailand has adopted antiretroviral treatment as prevention and HIV pre-exposure prophylaxis for men who have sex with men (MSM) and transgender women (TGW) as its core HIV control strategy. However, in the absence of reliable epidemiologic indicators, the impact of these policies on the course of the HIV epidemic in these groups remains unknown. To help answer this question, we formulated an HIV epidemic consensus initiative for Bangkok, Thailand, to analyze epidemiologic and program data and reach agreement between experts and stakeholders on the evolving state of the HIV epidemic among MSM and TGW. A customized Delphi process was used to consult and consolidate viewpoints of experts and stakeholders. Experts presented and discussed HIV prevalence and incidence data from recent and ongoing studies among MSM and TGW in Bangkok (2014 to 2018) during a meeting with stakeholders representing government, donors, and civil society. Agreement about the course of the HIV epidemic among MSM and TGW was attained by voting consensus. Based on presented data, meeting participants agreed that HIV prevalence and incidence had decreased among Bangkok MSM from 2014 to 2018. Despite these declines, HIV prevalence and incidence were found to remain high. This was particularly the case among younger MSM. Participants agreed that there was no evidence for a decrease in HIV prevalence and incidence among Bangkok TGW. Introduction of antiretroviral treatment as prevention and HIV pre-exposure prophylaxis may have contributed to these declines. However, HIV prevalence and incidence remained high, and no signs of a decrease were reported among Bangkok TGW. At the current rate of new HIV infections in MSM and TGW, Thailand will not reach its goal of ending AIDS by 2030. This HIV consensus initiative may serve as a model for building agreement and advocacy on epidemiologic and program data and their implications for a large metropolitan city.

We assessed HIV and syphilis infection among MSM and TGW attending Silom Community Clinic from 2017 to 2019. Walk-in and referral clients completed a registration application including a question on gender identity. We compared the prevalence of HIV, syphilis, and HIV and syphilis coinfection among TGW and MSM. In a total of 1050 clients, 276 (26.3%) were TGW and 774 (74.7%) were MSM. Among TGW clients, HIV prevalence was 29.8%, syphilis prevalence was 38.4%, and coinfection prevalence was 18.5%. Comparing prevalence among TGW to MSM, the adjusted prevalence ratio (aPR) for HIV was 1.8 (95% CI:1.4-2.3), for syphilis was 1.2 (95% CI:1.0-1.4), and for HIV and syphilis coinfection was 2.1 (95% CI:1.4-2.9). The prevalence of syphilis was higher than HIV among TGW, with a PR of 1.3 (95% CI:1.1-1.6), and among MSM, with a PR of 1.4 (95% CI:1.2-1.7). TGW age 15-21 years had an HIV prevalence of 16.9% and syphilis prevalence of 30.8%. After adjusting for age, referral, and sexual behaviors, TGW remain significantly associated with HIV and syphilis prevalence. There is a substantial burden of HIV and HIV/syphilis co-infection among TGW. HIV/STI prevention are needed for TGW, including linkage to HIV care.

The HIV epidemic in Thailand is concentrated in key populations, with the highest rates in men who have sex with men (MSM) and transgender women (TG). Previous studies of HIV incidence in these groups have been limited mostly to Bangkok. We measured HIV incidence in MSM and TG in four provinces and evaluated factors associated with incident infections to inform public health prevention efforts. An analysis was conducted using data collected during a prospective observational cohort study during April 2015-May 2018 in outpatient clinics in five hospitals across four provinces in Thailand. MSM and TG aged ≥18 years, who were not known to be HIV-infected, and who reported anal intercourse with a male or TG without a condom in the past six months were enrolled. Participants were followed-up every 6 months for 18 months with questionnaires and HIV testing. A total of 40 HIV seroconversions occurred during follow-up, resulting in an HIV incidence of 3.5 per 100 person-years (95% CI 2.5, 4.8). Multivariate analyses indicated that identifying as gay (adjusted hazard ratio [AHR] 4.9; 95% CI 1.7-14.2), having receptive anal sex in the past six months (AHR 3.6; 95% CI 1.4-9.5), using alcohol (AHR 3.3; 95% CI 1.3-8.3), and taking alkyl nitrites (AHR 4.4; 95% CI 1.7-11.2) in the past six months were all independently associated with HIV infection. Overall this study found a lower HIV incidence in the highest risk population in Thailand compared with similar studies in Bangkok. Accelerated prevention efforts are needed to make the goal of 'zero new infections' possible in Thailand.

OBJECTIVES: We assessed HIV-1 infection among men who have sex with men (MSM) attending Silom Community Clinic (SCC) in Bangkok, Thailand from 2005-2018. Since 2014, Thailand increased implementation of HIV prevention strategies including pre-exposure prophylaxis and Treatment as Prevention. METHODS: MSM attending SCC were tested for HIV using rapid tests. We assessed trends in HIV prevalence, incidence and compared incidence before and after 2014. RESULTS: From 2005-2018, 14,034 clients attended SCC for HIV testing. The HIV prevalence increased from 19.2% in 2005-2006 to 34.0% in 2010, remained stable until 2016 and decreased to 17.2% in 2018 (p < 0.0001). The HIV incidence was 4.1 per 100 person-years (PY), with an inverted U-shape trend and a peak in 2009 (p < 0.0001). Incidence among young MSM aged 13-21 years remained high at 10.0 per 100 PY. Among those aged 22-29 years, lower incidence was found from Q 3 2016, with a relative risk reduction of 46.2% (p <0.001); and a similar reduction among those aged >/= 30 years from Q4 2014, corresponding to scale up of HIV prevention strategies. CONCLUSION: We find a decline in HIV infection among MSM. However, incidence remained high among young MSM.

In Thailand, pre-exposure prophylaxis (PrEP) is recommended for human immunodeficiency virus (HIV) prevention among at-risk men who have sex with men (MSM). We modeled the impact of PrEP and condom use as independent and combined interventions on the estimated number of HIV infections among a hypothetical population of 10,000 MSM in Bangkok, Thailand. Our model demonstrated a 92% (95% confidence interval 89.7, 94.2) reduction in HIV infections among Thai MSM who took daily PrEP and self-reported using condoms correctly and consistently (100% condom use). Increased use of PrEP and condoms likely would have a substantial impact on the HIV epidemic in Thailand.

We analyzed the incidence and predictors of symptomatic repeat Neisseria gonorrhoeae (NG) infection among men who have sex with men (MSM) enrolled in the Bangkok MSM Cohort Study. Thai MSM aged ≥18 years were enrolled during 2006–2010 and followed every four months. At baseline, participants were screened for rectal and urethral NG and Chlamydia trachomatis (CT) infections using nucleic acid amplification testing (NAAT), rectal and pharyngeal NG by culture, and pharyngeal CT by NAAT. During follow-up, symptomatic participants were tested for NG infection by NAAT and Gram stain of rectal or urethral specimens. Among 1464 participants without NG infection at the baseline visit and having at least one follow-up visit, 11.2% (164/1464) developed symptomatic NG infection, for a total of 251 infections. Symptomatic repeat NG infection occurred in 28.0% (46/164) of participants. The incidence rate was 3.9 cases per 100 person-years. Baseline predictors of repeat symptomatic NG were as follows: unknown human immunodeficiency virus (HIV) status despite history of HIV testing, previous sexually transmitted infection diagnosis by physician, insertive-only anal intercourse without a condom, amyl nitrate use at baseline, CT infection at baseline, age 18–24 years, and being a student; HIV infection at baseline or during the study period was also associated with repeat symptomatic NG infection. © The Author(s) 2020.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is highly effective in the prevention of HIV acquisition, particularly for men who have sex with men (MSM). Questions remain on the benefits of PrEP and implementation strategies for those at occupational risk of HIV acquisition in sex work, as well as on methods to support adherence among young people who initiate PrEP. OBJECTIVE: The Combination Prevention Effectiveness study for young cisgender MSM and transgender women (TGW) aims to assess the effectiveness and cost-effectiveness of a combination intervention among HIV-uninfected young MSM and TGW engaged in sex work in Thailand. METHODS: This open-label, nonrandomized assessment compares the relative effectiveness of a combination prevention intervention with and without daily oral emtricitabine and tenofovir disoproxil fumarate (Truvada) PrEP with SMS-based adherence support. HIV-uninfected young MSM and TGW aged 18 to 26 years in Bangkok and Pattaya who self-report selling/exchanging sex at least once in the previous 12 months are recruited by convenience sampling and peer referral and are eligible regardless of their intent to initiate PrEP. At baseline, participants complete a standard assessment for PrEP eligibility and may initiate PrEP then or at any time during study participation. All participants complete a survey and HIV testing at baseline and every 3 months. Participants who initiate PrEP complete monthly pill pickups and may opt-in to SMS reminders. All participants are sent brief weekly SMS surveys to assess behavior with additional adherence questions for those who initiated PrEP. Adherence is defined as use of 4 or more pills within the last 7 days. The analytic plan uses a person-time approach to assess HIV incidence, comparing participant time on oral PrEP to participant time off oral PrEP for 12 to 24 months of follow-up, using a propensity score to control for confounders. Enrollment is based on the goal of observing 620 person-years (PY) on PrEP and 620 PY off PrEP. RESULTS: As of February 2019, 445 participants (417 MSM and 28 TGW) have contributed approximately 168 PY with 95% (73/77) retention at 12 months. 74.2% (330/445) of enrolled participants initiated PrEP at baseline, contributing to 134 PY of PrEP adherence, 1 PY nonadherence, and 33 PY PrEP nonuse/noninitiation. Some social harms, predominantly related to unintentional participant disclosure of PrEP use and peer stigmatization of PrEP and HIV, have been identified. CONCLUSIONS: The majority of cisgender MSM and TGW who exchange sex and participate in this study are interested in PrEP, report taking sufficient PrEP, and stay on PrEP, though additional efforts are needed to address community misinformation and stigma. This novel multilevel, open-label study design and person-time approach will allow evaluation of the effectiveness and cost-effectiveness of combination prevention intervention in the contexts of both organized sex work and exchanged sex. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/15354.

OBJECTIVE: To estimate time of HIV infection in participants from the Bangkok Tenofovir Study (BTS) with daily oral tenofovir disoproxil fumarate (TDF) for pre-exposure prophylaxis (PrEP) and relate infection with adherence patterns. DESIGN: We used the diversity structure of the virus population at the first RNA-positive sample to estimate the date of infection, and mapped these estimates to medication diaries obtained under daily directly observed therapy (DOT). METHODS: HIV genetic diversity was investigated in all 17 PrEP breakthrough infections and in 16 placebo recipients. We generated 10 to 25 HIV env sequences from each participant by single genome amplification, and calculated time since infection (and 95% confidence interval) using Poisson models of early virus evolution. Study medication diaries obtained under daily DOT were then used to compute the number of missed TDF doses at the approximate date of infection. RESULTS: Fifteen of the 17 PrEP breakthrough infections were successfully amplified. Of these, 13 were initiated by a single genetic variant and generated reliable estimates of time since infection (median=47 [IQR=35] days). Eleven of these 13 were under daily DOT at the estimated time of infection. Analysis of medication diaries in these 11 participants showed 100% adherence in five, 90-95% adherence in two, 55% adherence in one, and non-adherence in three. CONCLUSIONS: We estimated time of infection in participants from BTS and found several infections when high levels of adherence to TDF were reported. Our results suggest that the biological efficacy of daily TDF against parenteral HIV exposure is not 100%.

OBJECTIVE: To estimate time of HIV infection in participants from the Bangkok Tenofovir Study (BTS) with daily oral tenofovir disoproxil fumarate (TDF) for pre-exposure prophylaxis (PrEP) and relate infection with adherence patterns. DESIGN: We used the diversity structure of the virus population at the first RNA-positive sample to estimate the date of infection, and mapped these estimates to medication diaries obtained under daily directly observed therapy (DOT). METHODS: HIV genetic diversity was investigated in all 17 PrEP breakthrough infections and in 16 placebo recipients. We generated 10 to 25 HIV env sequences from each participant by single genome amplification, and calculated time since infection (and 95% confidence interval) using Poisson models of early virus evolution. Study medication diaries obtained under daily DOT were then used to compute the number of missed TDF doses at the approximate date of infection. RESULTS: Fifteen of the 17 PrEP breakthrough infections were successfully amplified. Of these, 13 were initiated by a single genetic variant and generated reliable estimates of time since infection (median=47 [IQR=35] days). Eleven of these 13 were under daily DOT at the estimated time of infection. Analysis of medication diaries in these 11 participants showed 100% adherence in five, 90-95% adherence in two, 55% adherence in one, and non-adherence in three. CONCLUSIONS: We estimated time of infection in participants from BTS and found several infections when high levels of adherence to TDF were reported. Our results suggest that the biological efficacy of daily TDF against parenteral HIV exposure is not 100%.

BACKGROUND: We identified correlates of sex-related pre-exposure prophylaxis (PrEP) adherence in HPTN067/ADAPT, a phase 2, open-label feasibility study of daily and nondaily regimens of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF)-based PrEP, among Thai men who have sex with men (MSM), and transgender women (TGW), Bangkok. METHODS: Participants were randomly assigned to one of three self-administered dosing regimens for 24 weeks: daily, time-driven, or event-driven. Demographic and behavioral information was obtained at screening. Pill-container opening was recorded with electronic dose monitoring, and self-reported information on PrEP use, sex events, and substance use was obtained during weekly interviews to confirm dose data. Sex-related PrEP adherence was calculated as the proportion of sex events covered by PrEP use (at least one tablet taken within 4 days before sex and at least one tablet taken within 24 hours after sex) to total sex events. We used multivariate modeling with sex event as the unit of analysis to evaluate correlates associated with sex-related PrEP adherence. RESULTS: Among 178 MSM and TGW, sex-related PrEP adherence was similar in the daily and time-driven arms (P = 0.79), both significantly greater than the event-driven arm (P = 0.02 compared to daily). Sex-related PrEP adherence by those reporting stimulant use (74.2%) was similar to those reporting other nonalcohol drug use (76.3%, P = 0.80), but lower than those reporting no substance use (84.6%, P = 0.04). In a multivariable model, randomization to the event-driven arm, a higher prestudy number of reported sex events, and use of stimulant drugs were associated with significantly lower sex-related PrEP adherence. CONCLUSION: Adherence was influenced by treatment schedule and adversely affected by nonalcoholic substance use. Regardless of these factors, Thai MSM and TGW maintained high adherence levels to oral PrEP dosing regimens and coverage of sexual exposures.

Background: Three consecutive prospective studies were conducted among people who inject drugs (PWID) from May 1995 through June 2012 in Bangkok, Thailand. We examined data from these studies to evaluate HIV incidence and explore trends in risk behaviours. Methods: We used data from a 1995–1998 cohort study, a 1999–2004 HIV vaccine trial, and a 2005–2012 HIV pre-exposure prophylaxis (PrEP) study to examine per-quarter trends in HIV incidence, using a restricted cubic spline function for time in a Poisson regression. We also examined temporal trends in HIV-associated risk behaviours. Findings: HIV incidence declined from 5.7 per 100 person-years during the cohort study, to 2.7 per 100 person-years in the vaccine trial, to 0.7 per 100 person-years among PrEP study placebo recipients. Incidence peaked at 12.1 per 100 person-years in 1996 and declined to < 1.0% during 2005–2012. Reports of injecting drugs and sharing needles also declined from the cohort study to the PrEP study (p < 0.0001). Heroin was the most common drug injected during the cohort study and the vaccine trial, but stimulants (e.g., methamphetamine) and sedatives (e.g., midazolam) were injected more often during the PrEP study. Interpretation: HIV incidence among PWID declined during 2005–2012. Several factors likely contributed to the decline, including decreases in the frequency of injecting and sharing, improved access to HIV testing and antiretroviral therapy, and the use of PrEP. Expanding access to effective HIV prevention tools can hasten control of the HIV epidemic among PWID. Funding: The Bangkok Metropolitan Administration and U.S. Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention.

Background: Approximately 1% of adults in Thailand are infected with hepatitis C virus (HCV). New direct-acting antiviral agents achieve sustained virologic responses in >95% of HCV-infected patients and are becoming available in countries around the world. To prepare for new HCV treatment options in Thailand, this study characterized HCV infections among people who inject drugs (PWID) in Bangkok. Methods: The Bangkok Tenofovir Study (BTS) was a pre-exposure prophylaxis trial conducted among PWID, 2005-2013. Blood specimens were randomly selected from PWID screened for the BTS, to test for anti-HCV antibody and HCV RNA. The HVR1 region was amplified by polymerase chain reaction, using multiplex primer sets with unique identifier sequences; amplification products were pooled in sets of 25; and consensus sequencing was performed to characterize individual HCV genotypes. Results: The median age of 3679 participants tested for anti-HCV antibody was 31 years, 3016 (82.0%) were male and 447 (12.2%) were HIV infected. The prevalence of anti-HCV antibody was 44.3%. The adjusted odds of testing positive for anti-HCV antibody were higher in men (adjusted odds ratio [aOR] 3.2, 95% confidence interval [CI] 2.4-4.3), those aged 40 years or older (aOR 2.7, 95% CI 2.1-3.5), those who had more than a primary school education (aOR 1.7, 95% CI 1.4-2.1), and those who tested HIV positive (aOR 5.2, 95% CI 3.7-7.4). HCV RNA was detected in 644 (81.3%) of the 792 anti-HCV antibody-positive specimens, yielding an HCV RNA-positive prevalence of 36.0% (95% CI 33.8-38.2). Among a random sample of 249 of the 644 specimens, 218 could be characterized, and the most common HCV subtypes were 1a (30.3%), 1b (12.8%), 3a (35.8%), 3b (6.9%) and 6n (8.7%). Conclusion: The prevalence of anti-HCV antibody among PWID was 44.3% and more than one third (36.0%) were HCV RNA positive. Genotypes 1, 3 and 6 accounted for all typable infections. As the government of Thailand considers introduction of direct-acting antiviral medications for people with hepatitis C, it will be important to ensure that the medications target these subtypes.

We describe incident human immunodeficiency virus (HIV) and syphilis trends in men who have sex with men (MSM) and transgender women (TGW) presenting for HIV voluntary counseling and testing (VCT) services and sexually transmitted infection (STI) management at the Silom Community Clinic, Bangkok, Thailand. Clients underwent rapid HIV testing and syphilis rapid plasma reagin (RPR) testing. For incidence analysis, we included clients with >1 follow-up visit. Initial negative HIV with subsequent positive HIV defined incident HIV infection; incident syphilis infection was defined as negative RPR followed by positive RPR (titer >/=1:8) and confirmatory anti- Treponema pallidum antibodies. Calculation of incidence using Poisson regression assumed a uniform probability distribution throughout the seroconversion interval. From 15 September 2005 to 31 December 2015, we tested 10,158 clients for HIV and 10,324 for syphilis. Overall, 7109 clients tested HIV-seronegative and contributed 7157 person-years (PY). Three-hundred forty-seven incident HIV infections resulted in an incidence rate of 4.8 per 100 PY (95% confidence interval [CI] 4.4-5.4). We found an inverted U-shape trend of HIV incidence over time with a peak of 6.4 per 100 PY in quarter 2/2011 ( p < 0.01) (Poisson with RCS function, p = 0.001). Overall, 8713 clients tested seronegative for syphilis and contributed 8623 PY. The incidence of syphilis infection was 4.4 per 100 PY (95% CI 3.9-4.8). Despite an apparent decline in HIV incidence among MSM and TGW attending VCT services, syphilis incidence rose and remained high. Evaluating temporal trends of HIV and syphilis incidence provides an opportunity to evaluate epidemic trajectories and target limited program funding. We recommend focused HIV and STI prevention interventions for MSM in Bangkok.

HIV incidence information is essential for epidemic monitoring and evaluating preventive interventions. However, reliable HIV incidence data is difficult to obtain, especially among marginalized populations, such as young men who have sex with men (YMSM). Here we evaluate the reliability of an alternative HIV incidence assessment method, behavioral imputation, as compared to serologically estimated HIV incidence. Recent HIV incidence among YMSM (aged 18 to 21 and 18 to 24 years) enrolled in a cohort study in Bangkok from 2006 to 2014 was estimated using two mid-point methods for seroconversion: 1) between age of first anal intercourse and first HIV-positive test (without previous HIV-negative test) (behavioral imputation) and 2) between the date of last negative and first positive HIV test (serological estimation). Serologically estimated HIV incidence was taken as the "gold standard" to evaluate between-method agreement. At baseline, 314 YMSM age 18 to 21 years accumulated 674 person-years (PY) of follow-up since first anal intercourse. Considering that 50 men had prevalent HIV infection, the behaviorally imputed HIV incidence was 7.4 per 100 PY. Of the remaining 264 HIV-negative men, 54 seroconverted for HIV infection during the study, accumulating 724 PY of follow-up and a serologically estimated HIV incidence of 7.5 per 100 PY. At baseline, 712 YMSM age 18 to 24 years (including 18 to 21-year-old men analyzed above) accumulated 2143 PY of follow-up since first anal intercourse. Considering that 151 men had prevalent HIV infection, the behaviorally imputed HIV incidence was 7.0 per 100 PY. Of the remaining 561 HIV-negative men, 125 seroconverted for HIV infection during the study, accumulating 1700 PY of follow-up and a serologically estimated HIV incidence of 7.4 per 100 PY. Behavioral imputation and serological estimation are in good agreement when estimating recent HIV incidence in YMSM.

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.

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.

High HIV incidence has been reported in young men who have sex with men (YMSM) in North America and Western Europe, but there are limited data from Southeast Asia suggesting MSM may be the driver of the HIV epidemic in this region. We described HIV incidence and risk factors among 494 YMSM enrolled in a cohort study in Bangkok, Thailand. The HIV incidence was 7.4 per 100 person-years. In multivariable analysis, reporting use of an erectile dysfunction drug in combination with club drugs, having receptive or both insertive and receptive anal intercourse with men, having hepatitis A infection, having rectal Chlamydia trachomatis, having hepatitis B infection prior to HIV seroconversion, and reporting not always using condoms with male steady partners were significantly associated with HIV incidence in YMSM. Reduction in new HIV infections in YMSM are critical to reach targets set by Thailand and the region.

BACKGROUND: Results of the randomised, double-blind, placebo-controlled Bangkok Tenofovir Study (BTS) showed that taking tenofovir daily as pre-exposure prophylaxis (PrEP) can reduce the risk of HIV infection by 49% in people who inject drugs. In an extension to the trial, participants were offered 1 year of open-label tenofovir. We aimed to examine the demographic characteristics, drug use, and risk behaviours associated with participants' uptake of and adherence to PrEP. METHODS: In this observational, open-label extension of the BTS (NCT00119106), non-pregnant, non-breastfeeding, HIV-negative BTS participants, all of whom were current or previous injecting drug users at the time of enrolment in the BTS, were offered daily oral tenofovir (300 mg) for 1 year at 17 Bangkok Metropolitan Administration drug-treatment clinics. Participant demographics, drug use, and risk behaviours were assessed at baseline and every 3 months using an audio computer-assisted self-interview. HIV testing was done monthly and serum creatinine was assessed every 3 months. We used logistic regression to examine factors associated with the decision to take daily tenofovir as PrEP, the decision to return for at least one PrEP follow-up visit, and greater than 90% adherence to PrEP. FINDINGS: Between Aug 1, 2013, and Aug 31, 2014, 1348 (58%) of the 2306 surviving BTS participants returned to the clinics, 33 of whom were excluded because they had HIV (n=27) or grade 2-4 creatinine results (n=6). 798 (61%) of the 1315 eligible participants chose to start open-label PrEP and were followed up for a median of 335 days (IQR 0-364). 339 (42%) participants completed 12 months of follow-up; 220 (28%) did not return for any follow-up visits. Participants who were 30 years or older (odds ratio [OR] 1.8, 95% CI 1.4-2.2; p<0.0001), injected heroin (OR 1.5, 1.1-2.1; p=0.007), or had been in prison (OR 1.7, 1.3-2.1; p<0.0001) during the randomised trial were more likely to choose PrEP than were those without these characteristics. Participants who reported injecting heroin or being in prison during the 3 months before open-label enrolment were more likely to return for at least one open-label follow-up visit than those who did not report injecting heroin (OR 3.0, 95 % CI 1.3-7.3; p=0.01) or being in prison (OR 2.3, 1.4-3.7; p=0.0007). Participants who injected midazolam or were in prison during open-label follow-up were more likely to be greater than 90% adherent than were those who did not inject midazolam (OR 2.2, 95% CI 1.2-4.3; p=0.02) or were not in prison (OR 4.7, 3.1-7.2; p<0.0001). One participant tested positive for HIV, yielding an HIV incidence of 2.1 (95% CI 0.05-11.7) per 1000 person-years. No serious adverse events related to tenofovir use were reported. INTERPRETATION: More than 60% of returning, eligible BTS participants started PrEP, which indicates that a substantial proportion of PWID who are knowledgeable about PrEP might be interested in taking it. Participants who had injected heroin or been in prison were more likely to choose to take PrEP, suggesting that participants based their decision to take PrEP, at least in part, on their perceived risk of incident HIV infection. FUNDING: US Centers for Disease Control and Prevention and the Bangkok Metropolitan Administration.

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.

BACKGROUND: HIV-infected persons are at increased risk for severe influenza, yet immune responses to standard dose intramuscular influenza vaccine are suboptimal in this population. Intradermal 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 (15mcg) intradermal (ID) versus standard dose (15mcg) intramuscular (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 post vaccination based on serum hemagglutination inhibition (HI) antibody titers against each vaccine strain. Adverse events 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 viral load and antiretroviral treatment. Percent seroconversion to all (ID 14% vs. IM 15%; p=0.8) or at least one (ID 69% vs. IM 68%; p=0.7) of the three vaccine strains did not differ significantly between ID versus IM vaccine recipients. A higher proportion of participants who received ID vaccine had mild injection site adverse events compared to participants who received IM vaccine (77% versus 27%). CONCLUSIONS: There were no significant differences in the immunogenicity of standard dose ID versus 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.

Women who inject drugs (WWID) are at higher risk of HIV compared with their male counterparts as a result of multiple factors, including biological, behavioral, and sociostructural factors, yet comparatively little effort has been invested in testing and delivering prevention methods that directly target this group. In this article, we discuss the need for expanded prevention interventions for WWID, focusing on 2 safe, effective, and approved, yet underutilized biomedical prevention methods: opiate agonist therapy (OAT) and oral pre-exposure prophylaxis (PrEP). Although both interventions are well researched, they have not been well examined in the context of gender. We discuss the drivers of women injectors' higher HIV risk, review the effectiveness of OAT and PrEP interventions among women, and explain why these new HIV prevention tools should be prioritized for WWID. There is substantial potential for impact of OAT and PrEP programs for WWID in the context of broader gender-responsive HIV prevention initiatives. Although awaiting efficacy data on other biomedical approaches in the HIV prevention research "pipeline," we propose that the scale-up and implementation of these proven, safe, and effective interventions are needed now.

OBJECTIVE: To describe participant adherence to daily oral tenofovir in an HIV preexposure prophylaxis (PrEP) trial, examine factors associated with adherence, and assess the impact of adherence on the risk of HIV infection. DESIGN: The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial conducted among people who inject drugs, 2005-2012. METHODS: Participants chose daily visits or monthly visits. Study nurses observed participants swallow study drug and both initialed a diary. We assessed adherence using the diary. We examined adherence by age group and sex and used logistic regression to evaluate demographics and risk behaviors as predictors of adherence and Cox regression to assess the impact of adherence on the risk of HIV infection. RESULTS: A total of 2413 people enrolled and contributed 9665 person-years of follow-up (mean 4.0 years, maximum 6.9 years). The risk of HIV infection decreased as adherence improved, from 48.9% overall to 83.5% for those with at least 97.5% adherence. In multivariable analysis, men were less adherent than women (P = 0.006) and participants 20-29 years old (P < 0.001) and 30-39 years old (P = 0.01) were less adherent than older participants. Other factors associated with poor adherence included incarceration (P = 0.02) and injecting methamphetamine (P = 0.04). CONCLUSION: In this HIV PrEP trial among people who inject drugs, improved adherence to daily tenofovir was associated with a lower risk of HIV infection. This is consistent with trials among MSM and HIV-discordant heterosexual couples and suggests that HIV PrEP can provide a high level of protection from HIV infection.

OBJECTIVES: We examined the causes of hospitalization and death of people who inject drugs participating in the Bangkok Tenofovir Study, an HIV preexposure prophylaxis trial. METHODS: The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial conducted during 2005 to 2012 among 2413 people who inject drugs. We reviewed medical records to define the causes of hospitalization and death, examined participant characteristics and risk behaviors to determine predictors of death, and compared the participant mortality rate with the rate of the general population of Bangkok, Thailand. RESULTS: Participants were followed an average of 4 years; 107 died: 22 (20.6%) from overdose, 13 (12.2%) from traffic accidents, and 12 (11.2%) from sepsis. In multivariable analysis, older age (40-59 years; P = .001), injecting drugs (P = .03), and injecting midazolam (P < .001) were associated with death. The standardized mortality ratio was 2.9. CONCLUSIONS: People who injected drugs were nearly 3 times as likely to die as were those in the general population of Bangkok and injecting midazolam was independently associated with death. Drug overdose and traffic accidents were the most common causes of death, and their prevention should be public health priorities.

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 55 per 100 person-years (95% CI 48-63), with an increasing trend (adjusted p=002). 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 53 per 100 person-years (95% CI 47-61), with an increase and then a decline (inverted U-shaped curve, p=00001). 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 229, 95% CI 188-278, p<00001) and BMCS cohorts (199, 150-265, p<00001). Overall, drug use (p=003), drug use to enhance sex (p=00006), use of drugs for erectile dysfunction (p<00001), and 100% condom use (p<00001) increased over time, whereas the proportion of individuals reporting receptive anal intercourse decreased (p=0004). 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.

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 4-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.

The HIV incidence among Thai men who have sex with men (MSM) enrolled in the Bangkok MSM Cohort Study (BMCS) has remained high since its inception in 2006. The purpose of this BMCS analysis was to determine: (1) changes in three HIV-risk behaviors (unprotected anal intercourse (UAI), recreational drug use, and multiple sexual partners i.e., more than four male/transgender partner) over time; and (2) factors associated with each one separately. Thai MSM aged 18 years or older and living in Bangkok were eligible to participate in the BMCS. At each follow-up visit, participants were asked to report their sexual and drug behaviors in the previous 4 months. We conducted a longitudinal analysis using generalized estimating equations logistic regression that included 1,569 MSM who were enrolled from 2006 to 2010 and contributed at least one follow-up visit. For each four-month visit increase, we found a 2, 1, and 1 % decrease in odds for reported UAI, recreational drug use, and multiple sexual partners, respectively. We found significant predictors associated with three HIV-risk behaviors such as binge drinking, participation in group sex, and use of erectile dysfunction drugs. The statistically significant decrease in odds of HIV-risk behaviors among the participants is encouraging; however, continued vigilance is required to address the factors associated with HIV-risk behaviors through currently available interventions reaching MSM.

BACKGROUND: Tenofovir disoproxil fumarate (tenofovir) has been associated with renal dysfunction in people infected with HIV receiving combination antiretroviral treatment. We reviewed data from an HIV pre-exposure 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<0.001) and CKD-EPI (p=0.007) equations, but not MDRD (p=0.12). Creatinine clearance measured when study drug was stopped was lower in the tenofovir than placebo group (p<0.001); but the difference resolved when tested a median of 20 months later (p=0.12). CONCLUSION: 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 pre-exposure prophylaxis.

INTRODUCTION: HIV spread rapidly among people who inject drugs in Bangkok in the late 1980s. In recent years, changes in drug use and HIV-associated risk behaviors have been reported. We examined data from the Bangkok Tenofovir Study, an HIV pre-exposure prophylaxis trial conducted among people who inject drugs, to assess participant risk behavior and drug use, and to identify risk factors for HIV infection. METHODS: The Bangkok Tenofovir Study was a randomized, double-blind, placebo-controlled trial. HIV status was assessed monthly and risk behavior every 3 months. We used generalized estimating equations logistic regression to model trends of injecting, needle sharing, drugs injected, incarceration, and sexual activity reported at follow-up visits; and proportional hazards models to evaluate demographic characteristics, sexual activities, incarceration, drug injection practices, and drugs injected during follow-up as predictors of HIV infection. RESULTS: The proportion of participants injecting drugs, sharing needles, and reporting sex with more than one partner declined during follow-up (p<0.001). Among participants who reported injecting at enrollment, 801 (53.2%) injected methamphetamine, 559 (37.1%) midazolam, and 527 (35.0%) heroin. In multivariable analysis, young age (i.e., 20-29 years) (p = 0.02), sharing needles (p<0.001), and incarceration in prison (p = 0.002) were associated with incident HIV infection. Participants reporting sex with an opposite sex partner, live-in partner, casual partner, or men reporting sex with male partners were not at a significantly higher risk of HIV infection compared to those who did not report these behaviors. CONCLUSION: Reports of HIV-associated risk behavior declined significantly during the trial. Young age, needle sharing, and incarceration were independently associated with HIV infection. Sexual activity was not associated with HIV infection, suggesting that the reduction in HIV incidence among participants taking daily oral tenofovir compared to those taking placebo was due to a decrease in parenteral HIV transmission.