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OBJECTIVE To evaluate associations between hair antiretroviral hair concentrations as an objective, cumulative adherence metric, with self-reported adherence and virologic outcomes. DESIGN Analysis of cohort A of the ACTG-A5288 study. These patients in resource-limited settings were failing second-line protease inhibitor-based antiretroviral therapy (ART) but were susceptible to at least one nucleoside reverse transcriptase inhibitor (NRTI) and their protease inhibitor, and continued taking their protease inhibitor-based regimen. METHODS Antiretroviral hair concentrations in participants taking two NRTIs with boosted atazanavir (n = 69) or lopinavir (n = 112) were analyzed at weeks 12, 24, 36 and 48 using liquid-chromatography--tandem-mass-spectrometry assays. Participants' self-reported percentage of doses taken in the previous month; virologic failure was confirmed HIV-1 RNA at least 1000 copies/ml at week 24 or 48. RESULTS From 181 participants with hair samples (61% women, median age: 39 years; CD4+ cell count: 167 cells/μl; HIV-1 RNA: 18 648 copies/ml), 91 (50%) experienced virologic failure at either visit. At 24 weeks, median hair concentrations were 2.95 [interquartile range (IQR) 0.49-4.60] ng/mg for atazanavir, 2.64 (IQR 0.73--7.16) for lopinavir, and 0.44 (IQR 0.11--0.76) for ritonavir. Plasma HIV-1 RNA demonstrated inverse correlations with hair levels (rs -0.46 to -0.74) at weeks 24 and 48. Weaker associations were seen with self-reported adherence (rs -0.03 to -0.24). Decreasing hair concentrations were significantly associated with virologic failure, the hazard ratio (95% CI) for ATV, LPV, and RTV were 0.69 (0.56-0.86), 0.77 (0.68-0.87), and 0.12 (0.06-0.27), respectively. CONCLUSION Protease inhibitor hair concentrations showed stronger associations with subsequent virologic outcomes than self-reported adherence in this cohort. Hair adherence measures could identify individuals at risk of second-line treatment failure in need of interventions.

BACKGROUND: The RV144 phase 3 vaccine trial in Thailand demonstrated that ALVAC-HIV (vCP1521) and AIDSVAX® B/E administration over six months resulted in a 31% efficacy in preventing HIV acquisition. In this trial, we assessed the immunologic impact of an additional vaccine boost to the RV144 regimen at varying intervals between the priming vaccine series and the boost. METHODS: RV306 is a double-blind, placebo-controlled, randomized clinical trial conducted in three clinical sites in Thailand. HIV-uninfected volunteers aged 20–40 randomly received the primary RV144 vaccine series at months 0, 1, 3, and 6, with no additional boost (Group I), additional AIDSVAX® B/E and ALVAC-HIV (vcp1521) at month 12 (Group II), AIDSVAX® B/E alone at month 12 (Group III), AIDSVAX® B/E and ALVAC-HIV at month 15 or 18 (Groups IVa or IVb), or placebo and were followed for 24 months. A randomization schedule was centrally generated with fixed sized strata for RIHES Chiang Mai (n=60) and combined Bangkok clinics (n=300). Primary outcomes were to assess the safety and tolerability of these vaccination regimens and characterize and compare cellular and humoral immune responses between the RV144 series alone and late boosts at different timepoints. Safety and tolerability outcomes were assessed by evaluating local and systemic reactogenicity and adverse events in all participants. Primary immunogenicity outcomes were evaluated by comparing peak humoral responses (HIV-specific IgG and IgA ELISA) and cellular responses (HIV-specific intracellular cytokine staining and polyfunctionality) two weeks post final vaccination among per-protocol participants who completed all vaccinations. This trial is registered at (ClinicalTrials.gov (NCT01931358); clinical follow up is now complete. FINDINGS: Between 28 October 2013 and 29 April 2014, 367 participants were enrolled, of whom 27 were assigned active vaccination in Group I, 102 in Group II, 101 in Group III, 52 in Group IVa, 51 in Group IVb, and 34 combined placebo across all groups. Late boosting did not induce vaccine-related serious adverse events. There were no significant differences in the occurrence or severity of local or systemic reactogenicity across active groups. Groups with late boosts (Groups II, III, IVa, and IVb) had increased peak plasma IgG binding antibody levels against gp70 V1V2 relative to Group I vaccine recipients with no late boost (gp70V1V2 92TH023 adjusted p < 0·02 for each; gp70V1V2 Case A2 adjusted p month 15 (Group IVa) > month 12 (Groups II+III) > no late boost (Group I). Groups with late boosts had increased both functionality and polyfunctionality scores relative to vaccine recipients with no late boost (all adjusted p < 0·05, except for polyfunctionality score in Group I vs in Group IVb p < 0·01). INTERPRETATION: Taken together, these results suggest that additional boosting of the RV144 regimen with longer intervals between the primary vaccination series and late boost improved immune responses and may improve the efficacy of preventing HIV acquisition. FUNDING: US National Institute of Allergy and Infectious Diseases (NIAID) and U.S. Department of the Army.

Background Human papilloma virus (HPV) load has been linked to cellular abnormalities of the uterine cervix, and proposed as predictors of HPV persistence and progression of dysplasia to cervical cancer. However, the association of HPV viral load and anal dysplasia and cancer has not been as thoroughly investigated. Objectives To examine the association of the viral loads of high-risk HPV types 16, 18, and 52, with the cytologic severity grading in anal-swab specimens of MSM with and without HIV-1 co-infection. Study design A cross-sectional study recruited 200 MSM in northern Thailand from July 2012 to January 2013. Real-time qPCR amplified portion of the HPV E6E7 gene, as well as the human β-globin gene to validate adequacy of the anal specimens and to normalize interpatient viral-load comparisons. Genotyping by linear-array assay identified and distinguished types 16, 18, and 52. Results HPV-16, and -18 viral loads increased with respect to the abnormality of the cytologic diagnoses ( p p p =0.006). HPV-16 viral loads ≥10 2.24 copies per 5000 anal cells, and HPV-18 loads ≥10 3.15 , were independently associated with abnormal cytology on logistic regression ( p =0.022, p =0.041, respectively). Positive predictive values were 85.2% (23/27) and 80.0% (44/55) for the high viral load of a particular HPV-16 and the combined HPV-16, -18 and -52 types, respectively. Conclusions High viral loads of HPV types 16 and 18 appear to be associated with anal cytologic abnormalities. The clinical utility of HPV viral loads to predict risk for anal cancer remains to be determined by a larger prospective cohort with sufficient frequency of high-grade dysplasia.

Introduction: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. Objective: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. Methods: 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350–550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation. Results: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. Conclusions: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.

HIV Prevention Trials Network (HPTN) 052 demonstrated that antiretroviral therapy (ART) prevents HIV transmission in serodiscordant couples. HIV from index-partner pairs was analyzed to determine the genetic linkage status of partner infections. Forty-six infections were classified as linked, indicating that the index was the likely source of the partner’s infection. Lack of viral suppression and higher index viral load were associated with linked infection. Eight linked infections were diagnosed after the index started ART: four near the time of ART initiation and four after ART failure. Linked infections were not observed when the index participant was stably suppressed on ART.

Background: Single nucleotide polymorphism of the hepatic cytochrome P450 isoenzyme 2B6 (CYP2B6) gene is a cause of variation in plasma efavirenz (EFV) concentrations. We aimed to determine the allelic distribution of CYP2B6 gene, plasma levels of EFV, the prevalence of clinical depression, and their correlations in northern Thai population. Methods: This was a cross-sectional study of HIV-infected patients on EFV-containing antiretroviral regimens for ≥48 weeks. A single blood specimen was collected for determination of the mid-dose plasma EFV concentration and CYP2B6- 516G>T polymorphism. The presence and severity of depression were assessed. Results: One hundred patients were enrolled [mean age (± SD) was 41.81 ± 8.44 years, mean CD4 lymphocyte count 462 ± 193 cells/ul]. The genotype CYP2B6-516 guanine/guanine (G/G), guanine/thymidine (G/T), and T/T were found in 49%, 37%, and 14% of patients, respectively. The allele frequency of CYP2B6-516 G to T replacement was 32.5%. The median plasma EFV concentration was 2,616 ng/mL (IQR 1,851-3,742); 79% had EFV plasma concentrations from 1,000 to 4,000 ng/mL. The mean EFV concentrations for those with G/G, G/T and T/T genotypes were 2,082±630, 3,166±1,074, and 11,196±6,265 ng/mL, respectively (p T polymorphism was the only factor associated with high plasma EFV levels. Nineteen patients had depression; 13 of 18 (72%) with mild and one with major depression had normal plasma EFV level. A weak correlation between plasma EFV concentrations and depression scores was observed (p=0.009, R2=0.059). Conclusions: The prevalence of CYP2B6-516G>T polymorphism in northern Thai population is high and strongly associated with inter-individual drug levels variation.

In late 2009, the Thai Ministry of Public Health provided two million doses of the monovalent pandemic influenza H1N1 2009 vaccine (Panenza®, Sanofi Pasteur), which was the only vaccine formulation available in Thailand, to persons at risk of more severe manifestations of the disease including HIV infection. Several studies have shown poorer immune responses to the 2009 H1N1 vaccines in HIV-infected individuals. There are limited data in this population in resource-limited countries.At day 28 post-vaccination, seroconversion was found in 32.0% (95%CI 24.5 - 40.2) of the HIV-infected group and 35.0% (95%CI 15.4- 59.2) of the healthy controls (p = 0.79). Seroprotection rate was observed in 33.3% (95%CI 25.8-41.6) and 35.0% (95%CI 15.4-59.2) of the HIV-infected group and the control group, respectively (p = 0.88). Among HIV-infected participants, the strongest factor associated with vaccine response was age 42 y or younger (p = 0.05).We evaluated the immunogenicity of a single, 15µg/0.5ml dose of a monovalent, non-adjuvanted 2009 H1N1 vaccine in 150 HIV-infected Thai adults and 20 healthy controls. Immunogenicity was measured by hemagglutination inhibition assay (HI) at baseline and 28 d after vaccination. Seroconversion was defined as 1) pre-vaccination HI titer1:10 and post-vaccination HI titer ≥ 1:40, or 2) pre-vaccination HI titer ≥ 1:10 and a minimum of 4-fold rise in post-vaccination HI titer. Seroprotection was defined as a post-vaccination HI titer of ≥ 1:40.A low seroconversion rate to the 2009 H1N1 vaccine in both study groups, corresponding with data from trials in the region, may suggest that the vaccine used in our study is not very immunogenic. Further studies on different vaccines, dosing, adjuvants, or schedule strategies may be needed to achieve effective immunization in HIV-infected population.

Background: HPV infection is common and may cause cancer among men who have sex with men (MSM). Anal HPV infection (HPV+) was found in 85% of HIV-positive (HIV+) and 59% of HIV-negative (HIV-) MSM in Bangkok, central Thailand. As little is known about HPV in this group in northern Thailand, we studied MSM subgroups comprised of gay men (GM), bisexual men (BM), and transgender women (TGW). Methods: From July 2012 through January 2013, 85 (42.5% of 200) GM, 30 (15%) BM, and 85 (42.5%) TGW who practiced receptive anal intercourse were recruited after informed consent, followed by self-assisted computer interview, HIV testing, and anal swabs for HPV genotyping. Results: Of 197 adequate specimens, the overall prevalence of any HPV was 157 (80%). Prevalence was 89% (76/85) in GM, 48% (14/29) in BM, and 81% (67/83) in TGW. The most common high-risk types were HPV16 (27% of 197), HPV58 (23%), and HPV51 (18%). Prevalence of high-risk types was 74% in 85 GM, 35% in 29 BM, and 71% in 83 TGW. Prevalence of any HPV type, or high-risk type, was 100% and 94%, respectively, among 48 HIV+ MSM, 70% and 54% among 120 HIV- MSM. Of the 197 specimens, 36% (70) had HPV types 16 and/or 18 in the bivalent vaccine, compared to 48% (95) with ?1 of types 16/18/06/11 in the quadrivalent, 56% (111) for 16/18/31/33/45/52/58 in the 7-valent, and 64% (126) for 16/18/31/33/45/52/58/06/11 in the 9-valent. HIV+, GM, and TGW were independently associated with HPV infection. Conclusions: We found higher rates of both any HPV and high-risk types than previous studies. Among the heretofore unstudied TGW, their equivalent HPV rates were comparable to GM. Current and investigational HPV vaccines could substantially protect GM, BM, and TGW from the serious consequences of HPV infection especially among HIV + MSM., PLOS ONE, 10(5), e0124499; 2015