HIV-1-infected cells presenting envelope glycoproteins (Env) in the CD4-bound conformation on their surface are preferentially targeted by antibodydependent cellular-mediated cytotoxicity (ADCC). HIV-1 has evolved sophisticated mechanisms to avoid the exposure of Env ADCC epitopes by downregulating CD4 and by limiting the overall amount of Env on the cell surface. In HIV-1, substitution of large residues such as histidine or tryptophan for serine 375 (S375H/W) in the gp120 Phe 43 cavity, where Phe 43 of CD4 contacts gp120, results in the spontaneous sampling of an Env conformation closer to the CD4-bound state. While residue S375 is well conserved in the majority of group M HIV-1 isolates, CRF01_ AE strains have a naturally occurring histidine at this position (H375). Interestingly, CRF01_AE is the predominant circulating strain in Thailand, where the RV144 trial took place. In this trial, which resulted in a modest degree of protection, ADCC responses were identified as being part of the correlate of protection. Here we investigate the influence of the Phe 43 cavity on ADCC responses. Filling this cavity with a histidine or tryptophan residue in Env with a natural serine residue at this position (S375H/W) increased the susceptibility of HIV-1-infected cells to ADCC. Conversely, the replacement of His 375 by a serine residue (H375S) within HIV-1 CRF01_AE decreased the efficiency of the ADCC response. Our results raise the intriguing possibility that the presence of His 375 in the circulating strain where the RV144 trial was held contributed to the observed vaccine efficacy.

AM in HIV-infected Thai women was 47.3 years, which is significantly earlier than the findings of a previous AM report on non-HIV-infected women. Postmenopausal HIV-infected women had more vasomotor and sexual symptoms. More studies are needed to investigate the cause and appropriate interventions for accelerated menopause in HIV-infected women.

Healthy Choices, a four-session motivational interviewing-based intervention, reduces risk behaviors among US youth living with HIV (YLWH). We randomized 110 Thai YLWH (16–25 years) to receive either Healthy Choices or time-matched health education (Control) over 12 weeks. Risk behaviors were assessed at baseline, 1, and 6 months post-session. The pilot study was not powered for between-group differences; there were no statistical differences in sexual risks, alcohol use, and antiretroviral adherence between the two groups at any visit. In within-group analyses, Healthy Choices group demonstrated decreases in the proportion of HIV-negative partners (20 vs 8.2 %, P = 0.03) and HIV sexual risk scores (4.3 vs 3.3, P = 0.04), and increased trends in the proportion of protected sex (57 vs 76.3 %, P = 0.07) from baseline to 1 month post-session. These changes were not sustained 6 months later. No changes were observed in Control group. Healthy Choices has potential to improve sexual risks among Thai YLWH.

In this cohort of children with low baseline CD4, half achieved immune recovery after 96 weeks of HAART. The predictors for immune recovery are younger children, female gender, high baseline CD4%, and long-term virologic suppression.

BackgroundThere are limited data of immunologic and virologic failure in Asian HIV-infected children using non-nucleoside reverse transcriptase inhibitor (NNRTI)-based highly active antiretroviral therapy (HAART). We examined the incidence rate of immunologic failure (IF) and virologic failure (VF) and the accuracy of using IF to predict VF in Thai HIV-infected children using first-line NNRTI-based HAART.MethodsAntiretroviral (ART)-naïve HIV-infected children from 2 prospective cohorts treated with NNRTI-based HAART during 2001-2008 were included. CD4 counts were performed every 12 weeks and plasma HIV-RNA measured every 24 weeks. Immune recovery was defined as CD4%≥25%. IF was defined as persistent decline of ≥5% in CD4% in children with CD4%<15% at baseline or decrease in CD4 count ≥30% from baseline. VF was defined as HIV-RNA>1,000 copies/ml after at least 24 weeks of HAART. Clinical and laboratory parameter changes were assessed using a paired t-test, and a time to event approach was used to assess predictors of VF. Sensitivity and specificity of IF were calculated against VF.Results107 ART-naive HIV-infected children were included, 52% female, % CDC clinical classification N:A:B:C 4:44:30:22%. Baseline data were median (IQR) age 6.2 (4.2-8.9) years, CD4% 7 (3-15), HIV-RNA 5.0 (4.9-5.5) log10copies/ml. Nevirapine (NVP) and efavirenz (EFV)-based HAART were started in 70% and 30%, respectively.At 96 weeks, none had progressed to a CDC clinical classification of AIDS and one had died from pneumonia. Overall, significant improvement of weight for age z-score (p = 0.014), height for age z-score, hemoglobin, and CD4 were seen (all p < 0.001). The median (IQR) CD4% at 96 weeks was 25 (18-30)%. Eighty-nine percent of children had immune recovery (CD4%≥25%) and 75% of children had HIV-RNA <1.7log10copies/ml.Thirty five (32.7%) children experienced VF within 96 weeks. Of these, 24 (68.6%) and 31 (88.6%) children had VF in the first 24 and 48 weeks respectively.Only 1 (0.9%) child experienced IF within 96 weeks and the sensitivity (95%CI) of IF to VF was 4 (0.1-20.4)% and specificity was 100 (93.9-100)%.ConclusionImmunologic failure, as defined here, had low sensitivity compared to VF and should not be recommended to detect treatment failure. Plasma HIV-RNA should be performed twice, at weeks 24 and 48, to detect early treatment failure.Trial RegistrationClinicaltrials.gov identification number NCT00476606

With disproportionately higher rates of HIV/AIDS among youth and increasing access to antiretroviral therapy (ART) in Thailand, there is a growing urgency in understanding the challenges to medication adherence confronting this population and in developing theory-based interventions to address these challenges. One potentially relevant model, the information-motivation-behavioral skills (IMB) model of adherence, was developed in Western settings characterized by a more individualistic culture in contrast to the more collectivistic culture of Thailand. We explored the application and adaptability of IMB on ART adherence among HIV-positive Thai youth through the analysis of qualitative data from a pilot motivational interviewing study. Twenty-two interview sessions from 10 HIV-positive Thai youth (17-24 years) were analyzed; 6 youth were on ART. Data support the utility of IMB as a potential framework for understanding ART adherence in this population. However, data indicate a consideration to expand the motivation construct of IMB to incorporate youths' perceived familial and social responsibilities and the need to adhere to medications for short-and long-term well-being of self, family, and society in a context of Buddhist values. These modifications to IMB could be relevant in other cultural settings with more collectivistic worldviews.

Motivational interviewing (MI) has been shown to reduce sexual risks among HIV-positive men who have sex with men (HMSM) in the U.S. We conducted a randomized trial of Healthy Choices, a 4-session MI intervention, targeting sexual risks among 110 HIV-positive youth ages 16–25 years in Thailand. Risk assessments were conducted at baseline, 1 month, and 6 months post-intervention. This report presents the analysis of 74 HMSM in the study. There were 37 HMSM in the Intervention group and 37 in the control group. The proportions of participants having anal sex and having sex with either HIV-uninfected or unknown partners in past 30 days were significantly lower in Intervention group than in control group at 6 months post-intervention (38% vs. 65%, p = .04; and 27% vs. 62%, p < .01, respectively). There were no significant differences in general mental health scores and HIV stigma scores between the two groups at any study visit. Thirty-five (95%) HMSM in the Intervention group vs. 31 (84%) in control group attended ≥3 sessions. Loss to follow-up was 8% and 30%, respectively (p = .04). Healthy Choices for young Thai HMSM was associated with sexual risk reduction. Improvements in mental health and HIV stigma were noted in Intervention group. Healthy Choices is a promising behavioral intervention and should be further developed to serve the needs of young HMSM in resource-limited countries.

Background Low bone mineral density (BMD) has been reported among 10–54% of HIV-infected adolescents in developed countries. We studied the prevalence and predictors of low BMD among HIV-infected Thai adolescents receiving antiretroviral therapy. Methods A cross-sectional study of lumbar spine (L2–L4) BMD as measured by dual-energy X-ray absorptiometry (DXA) in Thai HIV-infected adolescents aged 12–20 years was performed. The BMD Z-score was analyzed using age-matched healthy Thai children as a reference. Serum 25-hydroxyvitamin D (25-OHD) was performed. Osteopenia was defined as BMD Z-score≤ −2. Results From October 2010 to February 2011, 101 adolescents, 50% male, with a median age of 14.3 (range, 13.0–15.7) years were enrolled. The median (IQR) current CD4 T-cell count was 646 (506–796) cells/mm3 and 90% had plasma HIV-1 RNA <50 copies/ml. The mean BMD among HIV-infected adolescents and controls were 0.855 and 0.980 g/cm2(P<0.001). The median (IQR) L2–L4 spine BMD Z-score was −1.0 (−1.9 to −0.1), of which 24% had BMD Z-score ≤ −2.0. The median (IQR) of 25-OHD level was 24.8 (20.0–31.4) ng/ml, of which 25% had vitamin D level < 20 ng/ml. In multivariate analysis, the height for age Z-score <−1.5 (adjusted odds ratio (aOR) 6.2; 95% CI 2.2–17.7) and history of WHO clinical stage 4 prior to ART (aOR 3.7; 95%CI 1.3–10.7) were significantly associated with osteopenia. Conclusion One-fourth of HIV-infected Thai adolescents have osteopenia. Children with history of advanced- staging or having low height for age are at risk of osteopenia. Preventive measures to prevent osteopenia should be incorporated in routine care for these adolescents.