Bone mineral density changes among people living with HIV who have started with TDF-containing regimen: A five-year prospective study.

There are limited data regarding long-term BMD changes over time among treatment-naïve people living with HIV (PLHIV) after initiating combined antiretroviral therapy (cART) in Asia. We aimed to study bone mineral density (BMD) changes among treatment-naïve PLHIV started treatment with tenofovir disoproxil fumarate (TDF)- or non-TDF-containing regimen and HIV-uninfected controls in an Asian setting. The study was a five-year prospective study. BMD at lumbar spine (LS) (L1 to L4), total hip (TH), and femoral neck (FN) were measured by dual energy X-ray absorptiometry (DEXA) scans at baseline, months 12, 24 and 60. Multivariate logistic regression models were used to explore factors associated with mean BMD ≥5% reduction after 5 years of cART. A total of 106 PLHIV (75 and 31 started TDF- and non-TDF-containing regimen, respectively) and 66 HIV-uninfected individuals were enrolled. The mean percent changes of BMD were significantly different longitudinally between TDF and non-TDF users (p<0.001 for LS, p = 0.006 for TH and p = 0.02 for FN). HIV-positive status and on TDF-containing regimen was independently associated with BMD loss ≥5% at month 60 (adjusted odds ratio [aOR] 7.0, 95% confidence interval [95%CI] 2.3-21.0, P = 0.001 for LS; aOR 4.9, 95%CI 1.7-14.3, P = 0.003 for TH and aOR 4.3, 95%CI 1.6-11.2, P = 0.003 for FN) compared to HIV-uninfected individuals. In a multivariate model for PLHIV only, TDF use (vs. non-TDF, P = 0.005) and pre-treatment CD4+ count <350 cells/mm3 (vs. ≥350 cells/mm3, P = 0.02) were independently associated with ≥5% BMD loss in TH at month 60. Treatment-naïve PLHIV initiating treatment with TDF-containing regimen have higher BMD loss in a Thai cohort. TDF use and low pre-treatment CD4 count were independently associated with BMD loss at month 60 at TH. Earlier treatment initiation and interventions to prevent bone loss could improve skeletal health among PLHIV. Clinicaltrials.gov: NCT01634607.

Linkages to HIV confirmatory testing and antiretroviral therapy after online, supervised, HIV self-testing among Thai men who have sex with men and transgender women.

INTRODUCTION: Online, supervised, HIV self-testing has potential to reach men who have sex with men (MSM) and transgender women (TGW) who never tested before and who had high HIV-positive yield. We studied linkages to HIV confirmatory test and antiretroviral therapy (ART) initiation among Thai MSM and TGW who chose online and/or offline platforms for HIV testing and factors associated with unsuccessful linkages. METHODS: MSM and TGW were enrolled from Bangkok Metropolitan Region and Pattaya during December 2015 to June 2017 and followed for 12 months. Participants could choose between: 1) offline HIV counselling and testing (Offline group), 2) online pre-test counselling and offline HIV testing (Mixed group) and 3) online counselling and online, supervised, HIV self-testing (Online group). Sociodemographic data, risk behaviour and social network use characteristics were collected by self-administered questionnaires. Linkages to HIV confirmatory testing and/or ART initiation were collected from participants who tested reactive/positive at baseline and during study follow-up. Modified Poisson regression models identified covariates for poor retention and unsuccessful ART initiation. RESULTS: Of 465 MSM and 99 TGW, 200 self-selected the Offline group, 156 the Mixed group and 208 the Online group. The Online group demonstrated highest HIV prevalence (15.0% vs. 13.0% vs. 3.4%) and high HIV incidence (5.1 vs. 8.3 vs. 3.2 per 100 person-years), compared to the Offline and Mixed groups. Among 60 baseline HIV positive and 18 seroconversion participants, successful ART initiation in the Online group (52.8%) was lower than the Offline (84.8%) and Mixed groups (77.8%). Factors associated with unsuccessful ART initiation included choosing to be in the Online group (aRR 3.94, 95% CI 1.07 to 14.52), <17 years old at first sex (aRR 3.02, 95% CI 1.15 to 7.92), amphetamine-type stimulants use in the past six months (aRR 3.6, 95% CI 1.22 to 10.64) and no/single sex partner (aRR 3.84, 95%CI 1.36 to 10.83) in the past six months. CONCLUSIONS: Online, supervised, HIV self-testing allowed more MSM and TGW to know their HIV status. However, linkages to confirmatory test and ART initiation once tested HIV-reactive are key challenges. Alternative options to bring HIV test confirmation, prevention and ART services to these individuals after HIV self-testing are needed.

Antiretroviral-naïve HIV-infected patients had lower bone formation markers than HIV-uninfected adults.

There are limited studies regarding bone health among people living with HIV (PLHIV) in Asia. We compared bone mineral density (BMD), serum 25-hydroxyvitamin D (25(OH)D) status and bone turnover markers (serum procollagen type1 N-terminal propeptide (P1NP), osteocalcin (OC) and C-terminal cross-linking telopeptide of type1 collagen) among 302 antiretroviral therapy (ART) naive PLHIV compared to 269 HIV-uninfected controls from Thailand. People aged ≥30 years, with and without HIV infection (free of diabetes, hypertension, and active opportunistic infection) were enrolled. BMD at the lumbar spine, total hip, and femoral neck were measured using Hologic DXA at baseline and at 5 years. We analyzed BMD, serum 25(OH)D levels, and bone turnover markers at the patients' baseline visit. PLHIV were 1.5 years younger and had lower BMI. PLHIV had higher mean serum 25(OH)D level and similar BMD to the controls. Interestingly, PLHIV had significantly lower bone formation (serum P1NP and OC), particularly those with low CD4 count. Only a few participants had low bone mass. ARV naïve middle-aged PLHIV did not have lower BMD or lower vitamin D levels compared to the controls. However, PLHIV had lower bone formation markers, particularly those with low CD4 count. This finding supports the benefit of early ART.

An Integrated Approach to HIV Disclosure for HIV-Affected Families in Thailand.

Disclosure of HIV status to family members could improve communication, relationship, and cohesion. We evaluated the impact of a family-centered program designed to increase the readiness/willingness of parents to disclose HIV status to their children. People living with HIV (PLWH) with children ≥8 years were surveyed regarding HIV knowledge, family relationship, attitudes, willingness/readiness to disclose, and they were then invited to participate in group education and family camps. Of 367 PLWH surveyed, 0.8% had disclosed, 14.7% had not yet disclosed but were willing/ready to disclose, 50.4% were willing but not ready, and 33.2% did not wish to disclose. The educational sessions and camps led to significant improvements of HIV knowledge and disclosure techniques, and readiness/willingness to disclose. Given the benefits of group education and family camps in supporting PLWH to improve their communication with their families and disclose their HIV status, these supporting activities should be included in HIV programs.

Characterization of Cellular Immune Responses in Thai Individuals With and Without HIV-Associated Neurocognitive Disorders.

HIV-associated neurocognitive disorder (HAND) remains a challenge despite antiretroviral therapy (ART), and has been linked to monocyte/macrophage (M/M) migration to the brain. Due to the potential impact of T cell effector mechanisms in eliminating activated/HIV-infected M/M, T cell activation may play a role in the development of HAND. We sought to investigate the relationship between cognition and both CD8+ T cell activation (HLA-DR+/CD38+) and HIV-specific CD8+ T cell responses at the time of HIV diagnosis and 12 months postinitiation of ART. CD8+ T cell activation was increased in HAND compared to cognitive normal (NL) individuals and correlated directly with plasma viral load and inversely with the cognitive status. In addition, Gag-specific cytolytic activity (CD107a/b+) was decreased in HAND compared with NL individuals and correlated with their neurological testing, suggesting a potential role of cytotoxic CD8+ T cells in the mechanism of HAND development.

Neuronal-Glia Markers by Magnetic Resonance Spectroscopy in HIV Before and After Combination Antiretroviral Therapy.

OBJECTIVE: Combination antiretroviral therapy (cART) can suppress plasma HIV RNA to undetectable levels; yet reports indicate persistent HIV-associated neurocognitive disorders (HAND) among treated individuals. We sought to investigate imaging correlates of incomplete cognitive recovery among individuals with chronic HIV. METHODS: We used single voxel proton magnetic resonance spectroscopy in 4 regions of the brain to measure changes in neuronal and glia biomarkers in cART-naive subjects before (n = 59, 27 with HAND) and after 12 months of cART. RESULTS: At baseline, we observed elevated total choline (CHO) in the basal ganglia (BG, P = 0.002) and in the posterior cingulate gyrus (PCG, P = 0.022) associated with HIV infection. Myo-inositol (MI) was elevated in the frontal white matter (FWM, P = 0.040). N-acetylaspartate was elevated in the BG (P = 0.047). Using a mixed model approach among all HIV-infected individuals, at 6 months, we observed decreased n- acetylaspartate in FWM (P = 0.031), decreased creatine in PCG (P = 0.026) and increased MI in frontal gray matter (FGM, P = 0.023). At 12 months, we observed an increase in BG MI (P = 0.038) and in FGM (P = 0.021). Compared to those with normal cognition, HAND cases had higher FGM MI (P = 0.014) at baseline. At 12 months, individuals that remained cognitively impaired compared with those without HAND exhibited elevated CHO in the PCG (P = 0.018) and decreased glutamate in both FWM (P = 0.027) and BG (P = 0.013). CONCLUSIONS: cART started during chronic HIV is associated with reduced neuronal-glia and inflammatory markers. Alterations in CHO are noted among individuals who remain impaired after 12 months of cART.

Distal leg epidermal nerve fiber density as a surrogate marker of HIV-associated sensory neuropathy risk: risk factors and change following initial antiretroviral therapy.

Distal leg epidermal nerve fiber density (ENFD) is a validated predictor of HIV sensory neuropathy (SN) risk. We assessed how ENFD is impacted by initiation of first-time antiretroviral therapy (ART) in subjects free of neuropathy and how it is altered when mitochondrial toxic nucleoside medications are used as part of ART. Serial changes in proximal thigh and distal leg ENFD were examined over 72 weeks in 150 Thai subjects randomized to a regimen of stavudine (d4T) switching to zidovudine (ZDV) at 24 weeks vs ZDV vs tenofovir (TDF) for the entire duration of study, all given in combination with nevirapine. We found individual variations in ENFD change, with almost equal number of subjects who decreased or increased their distal leg ENFD over 72 weeks and no relationship to nucleoside backbone or to development of neuropathic signs or symptoms. Lower baseline distal leg ENFD and greater increases in mitochondrial oxidative phosphorylation complex I (CI) activity were associated with larger increases in distal leg ENFD over 72 weeks. Distal leg ENFD correlated with body composition parameters (body surface area, body mass index, height) as well as with blood pressure measurements. Assessed together with a companion cross-sectional study, we found that mean distal leg ENFD in all HIV+ subjects was lower than in HIV- subjects but similar among HIV+ groups whether ART-naïve or on d4T with/without neuropathy/neuropathic symptoms. The utility of ENFD as a useful predictor of small unmyelinated nerve fiber damage and neuropathy risk in HIV may be limited in certain populations.

Epidermal nerve fiber density, oxidative stress, and mitochondrial haplogroups in HIV-infected Thais initiating therapy.

OBJECTIVE: We explored associations between mitochondrial DNA (mtDNA) haplogroups, epidermal nerve fiber density (ENFD), and HIV-associated sensory neuropathy (HIV-SN) in a randomized trial of Thai patients initiating antiretroviral therapy (ART). DESIGN: The South East Asia Research Collaboration with Hawaii 003 study evaluated toxicity of nucleoside reverse transcriptase inhibitors (stavudine vs. zidovudine vs. tenofovir). We present secondary analyses of mtDNA haplogroups and ENFD changes. METHODS: ENFD, peripheral blood mononuclear cell mitochondrial complex I and IV, and 8-oxo-deoxyguanine (8-oxo-dG) were quantified. Peripheral blood mononuclear cell mtDNA sequences were obtained for haplogroup determination. Multivariate regression of ENFD change was performed. RESULTS: Paired ENFD was available from 118 patients. Median age, CD4 cell count, and height at entry were 34 years, 172 cells/µl, and 162 cm, respectively. Major haplogroups included M (42%), F (21%), and B (16%). Baseline ENFD, CD4 cell count, randomized ART, and biomarkers did not differ by haplogroup. Haplogroup B patients were older (P=0.02) at baseline, and had an increase in median ENFD (+1.5 vs. -2.9 fibers/mm; P=0.03) and 8-oxo-dG break frequency (+0.05 vs. 0.00; P=0.05) compared to other haplogroups. In a multivariate model, haplogroup B was associated with increased ENFD (ß=3.5, P=0.009) at week 24, whereas older age (P=0.02), higher baseline CD4 cell count, (P=0.03), higher complex I level (P=0.03), and higher ENFD (P<0.001) at baseline were all associated with decreased ENFD. Three of the six HIV-SN cases were haplogroup B (P=0.05). CONCLUSIONS: Thai persons belonging to mtDNA haplogroup B had increased ENFD and 8-oxo-dG on ART, and were more likely to develop HIV-SN. These results suggest that mtDNA variation influences early oxidative damage and ENFD changes.

A 72-week randomized study of the safety and efficacy of a stavudine to zidovudine switch at 24 weeks compared to zidovudine or tenofovir disoproxil fumarate when given with lamivudine and nevirapine.

BACKGROUND: Due to superior long-term toxicity profiles, zidovudine (AZT) and tenofovir disoproxil fumarate (TDF) are preferred over stavudine (d4T) for first-line antiretroviral regimens. However, short-term d4T use could be beneficial in avoiding AZT-induced anaemia. METHODS: We randomized (1:1:1) 150 treatment-naive Thai HIV-infected adults with CD4(+) T-cell count <350 cells/mm(3) to arm 1 (24-week GPO-VIR S30(®) [d4T plus lamivudine (3TC) plus nevirapine (NVP)] followed by 48-week GPO-VIR Z250(®) [AZT plus 3TC plus NVP]), arm 2 (72-week GPO-VIR Z250(®)) or arm 3 (72-week TDF plus emtricitabine [FTC] plus NVP). Haemoglobin (Hb), dual energy x-ray absorptiometry, neuropathic signs, estimated glomerular filtration rate (eGFR), CD4(+) T-cell count, plasma HIV RNA and adherence were assessed. RESULTS: In an intention-to-treat analysis, mean Hb decreased from baseline to week 24 in arm 2 compared with arm 1 (-0.19 versus 0.68 g/dl; P=0.001) and arm 3 (0.48 g/dl; P=0.010). Neuropathic signs were more common in arm 2 compared with arm 3 (20.4 versus 4.2%; P=0.028) at week 24. There were no differences in changes in peripheral fat and eGFR from baseline to weeks 24 and 72 among arms. CD4(+) T-cell count increased more in arm 1 than arms 2 and 3 from baseline to week 24 (168 versus 117 and 118 cells/mm(3); P=0.01 and 0.02, respectively) but the increase from baseline to week 72 was similar among arms. CONCLUSIONS: A 24-week d4T lead-in therapy caused less anaemia and greater initial CD4(+) T-cell count increase than initiating treatment with AZT. This strategy could be considered in patients with baseline anaemia or low CD4(+) T-cell count. If confirmed in a larger study, this may guide global recommendations on antiretroviral initiation where AZT is more commonly used than TDF.

Acceptability of male circumcision for the prevention of HIV among high-risk heterosexual men in Thailand.

Limited data are available on circumcision prevalence and acceptability among Thai men to prevent human immunodeficiency virus. Of 408 high-risk heterosexual men, 12.3% were circumcised. 14.2% and 24.9% expressed willingness to be circumcised before and after circumcision education, respectively. Neonatal circumcision acceptability was relatively high. One participant underwent circumcision at 3-month follow-up.

The prevalence of Helicobacter pylori infection in patients with gastrointestinal symptoms in Chon Buri, Thailand.

The prevalence of Helicobacter pylori infection varies between different geographic locations. The objectives of this study were to determine the prevalence of H. pylori infection in patients with gastrointestinal (GI) symptoms and to describe the association of H. pylori infection with demographic data, clinical diagnosis, and previous histories of patients. The study was carried out at the gastroenterology unit of Queen Sawang Wattana Memorial Hospital, Chon Buri, Thailand. The diagnosis of H. pylori infection was done by culture and rapid urease test on the gastric biopsy specimens of 112 patients. The overall prevalence of H. pylori infection by the gastric biopsy-based method was 58%. The prevalence of H. pylori infection in duodenal ulcer (DU) patients (75%) was significantly higher than in gastric ulcer (GU) patients (56.4%) and patients with gastritis (44.1%). A reverse correlation was observed between H. pylori infection and household income. The prevalence of H. pylori infection in patients who usually consumed unboiled water was 61.6%, which was significantly higher than in those who consumed boiled water (30.8%). We conclude that the prevalence of H. pylori infection in patients with GI symptoms is relatively high, and H. pylori infection is associated with DU disease. The data suggests that the household income and not boiling drinking water are related to the high H. pylori infection in our study.