An Open-Label Pharmacokinetic and Pharmacodynamic Assessment of Tenofovir Gel and Oral Emtricitabine/Tenofovir Disoproxil Fumarate.

The Microbicide Trials Network-017 study was undertaken to characterize the safety, acceptability, pharmacokinetic (PK), and pharmacodynamic profile of the reduced-glycerin (RG) 1% tenofovir (RG-TFV) gel compared to oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). The study was a Phase 2, three-period, randomized sequence, open-label, expanded safety and acceptability crossover study. In each 8-week study period, HIV-1-uninfected participants were randomized to RG-TFV rectal gel daily or RG-TFV rectal gel before and after receptive anal intercourse (RAI) (or at least twice weekly in the event of no RAI), or daily oral FTC/TDF. A mucosal substudy was conducted at sites in the United States and Thailand. Samples were collected to evaluate PK and ex vivo biopsy challenge with HIV-1. A total of 195 men who have sex with men and transgender women were enrolled in the parent study and 37 in the mucosal substudy. As previously reported, both products were found to be safe and acceptable. Systemic TFV concentrations were significantly higher following oral exposure and daily rectal administration compared to RAI-associated product use (p < .001). All three routes of pre-exposure prophylaxis (PrEP) administration resulted in the inhibition of explant infection (p < .05), and there was a significant inverse correlation between explant HIV-1 p24 and tissue concentrations of TFV and FTC (p < .0001). Despite significant differences in systemic and mucosal drug concentrations, all three PrEP regimens were able to protect rectal explants from ex vivo HIV infection. These data suggest that there is a rationale for co-development of oral and topical antiretroviral PrEP for HIV prevention. Clinical Trial Registration number: NCT01687218.

Complete Genome Sequences of Three Neisseria gonorrhoeae Isolates from Thailand with Multidrug Resistance and Multilocus Sequence Type 1903.

Multilocus sequence typing (MLST) sequence type 1903 (ST1903) is the most common ST of ceftriaxone-resistant Neisseria gonorrhoeae Here, we report three completed genome sequences of MLST ST1903 N. gonorrhoeae isolates collected from patients at Faculty of Medicine Siriraj Hospital, a university hospital in Bangkok, Thailand, in 2009 to 2011.

Hepatitis C virus infection among people who inject drugs in Bangkok, Thailand, 2005-2010.

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.

Selling and buying sex in the city: men who have sex with men in the Bangkok men who have sex with men Cohort Study.

We describe participants in the Bangkok Men who have sex with men Cohort Study (BMCS) who sold or bought sex. Men who have sex with men (MSM) and transgender women aged ≥18 years had HIV testing and behavioral data collected at enrollment and every four months. We evaluated report of receiving money or goods for sex (selling sex) or giving money or goods for sex (buying sex) at enrollment using logistic regression models; we also describe sex work over time, and HIV and syphilis incidence among those who report sex work. At enrollment, 511 (29.3%) of 1744 participants reported buying or selling sex. Factors associated with selling sex were young age, lower education, living alone or living with a friend, being unemployed, higher HIV knowledge, binge drinking and club drug use, a higher number of casual male partners, meeting sex partners at specific venues, having a foreign sex partner, and being HSV-1 seropositive. MSM aged 18-21 years who sold sex had an HIV incidence of 11.1 per 100 person-years (95% CI: 6.7-17.4). Almost one-third of participants from BMCS reported sex work at enrollment. Young men who sold sex had high HIV incidence and HIV prevention interventions are needed for this at-risk population in Bangkok, Thailand.

Young Men Who Have Sex with Men at High Risk for HIV, Bangkok MSM Cohort Study, Thailand 2006-2014.

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.

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.

Recalibration of the limiting antigen avidity EIA to determine mean duration of recent infection in divergent HIV-1 subtypes.

BACKGROUND: Mean duration of recent infection (MDRI) and misclassification of long-term HIV-1 infections, as proportion false recent (PFR), are critical parameters for laboratory-based assays for estimating HIV-1 incidence. Recent review of the data by us and others indicated that MDRI of LAg-Avidity EIA estimated previously required recalibration. We present here results of recalibration efforts using >250 seroconversion panels and multiple statistical methods to ensure accuracy and consensus. METHODS: A total of 2737 longitudinal specimens collected from 259 seroconverting individuals infected with diverse HIV-1 subtypes were tested with the LAg-Avidity EIA as previously described. Data were analyzed for determination of MDRI at ODn cutoffs of 1.0 to 2.0 using 7 statistical approaches and sub-analyzed by HIV-1 subtypes. In addition, 3740 specimens from individuals with infection >1 year, including 488 from patients with AIDS, were tested for PFR at varying cutoffs. RESULTS: Using different statistical methods, MDRI values ranged from 88-94 days at cutoff ODn = 1.0 to 177-183 days at ODn = 2.0. The MDRI values were similar by different methods suggesting coherence of different approaches. Testing for misclassification among long-term infections indicated that overall PFRs were 0.6% to 2.5% at increasing cutoffs of 1.0 to 2.0, respectively. Balancing the need for a longer MDRI and smaller PFR (<2.0%) suggests that a cutoff ODn = 1.5, corresponding to an MDRI of 130 days should be used for cross-sectional application. The MDRI varied among subtypes from 109 days (subtype A&D) to 152 days (subtype C). CONCLUSIONS: Based on the new data and revised analysis, we recommend an ODn cutoff = 1.5 to classify recent and long-term infections, corresponding to an MDRI of 130 days (118-142). Determination of revised parameters for estimation of HIV-1 incidence should facilitate application of the LAg-Avidity EIA for worldwide use.

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.

An evaluation of hepatitis B virus diagnostic methods and responses to antiretroviral therapy among HIV-infected women in Thailand.

Coinfection with HIV and hepatitis B virus (HBV) is common in resource-limited settings but is frequently not diagnosed. The authors retrospectively tested specimens for HBV in HIV-infected Thai women who had participated in an antiretroviral therapy (ART) clinical study. A substantial proportion (27 of 211; 13%) of HIV-infected women were HBV coinfected. Among HIV/HBV-coinfected women, the authors observed similar rates of antiretroviral-associated liver toxicity (despite nevirapine [NVP] use) and CD4 count reconstitution as observed in HIV-monoinfected women. Hepatitis B surface antigen (HBsAg) screening detected the majority (81%) of HBV coinfections, including all 5 HBV-coinfected women who did not suppress HBV despite 48 weeks of lamivudine (3TC)-containing ART and could be used to tailor ART for patients diagnosed with HBV coinfection in accordance with World Health Organization guidelines. Although HBsAg screening did not diagnose 5 occult HBV coinfections, these women achieved HBV suppression on 3TC-containing ART, suggesting that not detecting occult HBV coinfection would have limited clinical impact.

Association of Nevirapine Levels with Rash or Hepatotoxicity Among HIV-Infected Thai Women.

BACKGROUND: We performed a nested case-control study of Thai women prescribed nevirapine-based antiretroviral therapy (ART) to determine if development of rash or hepatotoxicity during the first 24 weeks of treatment is associated with plasma nevirapine concentrations. METHOD: From May 2005-January 2007, we enrolled 217 women initiating nevirapine-based ART in Thailand. Cases (n = 54) were women who during the first 24 weeks of treatment with nevirapine developed rash (any grade, n = 42) or hepatotoxicity (≥grade 2, n = 22, [10 had both]). Controls were the next enrolled woman who was confirmed not to meet the case definition during the first 24 weeks. Nevirapine concentrations after the two week lead-in dose of 200 mg once daily were compared between cases and controls by Wilcoxon rank-sum tests. RESULTS: We found no difference in Week 2 pre-dose nevirapine concentrations: cases median = 3,528 ng/mL (n = 24), controls median = 3,150ng/mL (n = 30), p = 0.5. Cases had higher post-dose nevirapine concentrations (median = 6,150 ng/mL, n = 21) than controls (median = 4,746 ng/mL, n = 20, p = 0.02). When limited to cases who developed a rash at Week 2, we found no differences in the pre-dose (median = 3,270 ng/mL, n = 12, p = 0.9) or post-dose nevirapine concentration (median = 5,443 ng/mL, n = 9, p = 0.4) compared with controls. CONCLUSIONS: We cannot conclude definitively that nevirapine concentrations at two weeks of therapy are associated with rash or hepatotoxicity. It is unlikely that therapeutic drug monitoring at that time will improve identification of patients at risk for rash or hepatotoxicity.

Comparison of four reverse transcription-polymerase chain reaction procedures for the detection of dengue virus in clinical specimens.

The sensitivity of dengue virus identification by mosquito inoculation and four reverse transcription-polymerase chain reaction (RT-PCR) procedures (Am. J. Trop. Med. Hyg. 45 (1991) 418 (H); J. Clin. Microbiol. 29 (1991) 2107 (M); J. Clin. Microbiol. 30 (1992) 545 (L); and Southeast Asian J. Trop. Med. Public Health 27 (1996) 228 (Y)) were compared using coded clinical specimens derived from areas in Thailand where all four dengue serotypes circulate. The sensitivity of virus detection in serologically confirmed dengue cases was 54, 52, 60, 79, and 80% for mosquito inoculation, procedures H, M, L and Y, respectively. In comparison to clinical specimens which yielded virus isolates by mosquito inoculation, there was relatively low sensitivity in detecting each of the four dengue serotypes by PCR: procedure H-dengue 4 (25%), procedure M-dengue 3 (73%), procedure L-dengue 1 (70%), and procedure Y-dengue 1 (79%). Dengue virus was detectable by RT-PCR for more days of illness and in the presence of dengue-specific antibody when compared to virus isolated in mosquitoes. Procedures L and Y were more sensitive than mosquito inoculation or procedures H and M in detecting all four dengue serotypes in clinical specimens and may be the RT-PCR methods of choice for virus surveillance or research use.