Vitamin D3 Supplementation Increases Spine Bone Mineral Density in Adolescents and Young Adults With Human Immunodeficiency Virus Infection Being Treated With Tenofovir Disoproxil Fumarate: A Randomized, Placebo-Controlled Trial.

Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized that vitamin D3 (VITD3) would increase BMD in youth receiving TDF. Methods: This was a randomized, double-blind, placebo-controlled trial of directly observed VITD3 vs placebo every 4 weeks for 48 weeks in youth aged 16-24 years with HIV, RNA load <200 copies/mL, taking TDF-containing combination antiretroviral therapy (TDF-cART) for ≥180 days. Participants (N = 214) received a daily multivitamin containing VITD3 400 IU and calcium 162 mg, plus monthly randomized VITD3 50000 IU (n = 109) or placebo (n = 105). Outcome was change from baseline to week 48 in lumbar spine BMD (LSBMD). Data presented are median (Q1, Q3). Results: Participants were aged 22.0 (21.0, 23.0) years, 84% were male, and 74% were black/African American. At baseline, 62% had 25-hydroxy vitamin D (25-OHD) <20 ng/mL. Multivitamin adherence was 49% (29%, 69%), and VITD3/placebo adherence 100% (100%, 100%). Vitamin D intake was 2020 (1914, 2168) and 284 (179, 394) IU/day, and serum 25-OHD concentration was 36.9 (30.5, 42.4) and 20.6 (14.4, 25.8) ng/mL at 48 weeks in VITD3 and placebo groups, respectively (P < .001). From baseline to week 48, LSBMD increased by 1.15% (-0.75% to 2.74%) in the VITD3 group (n = 99; P < .001) and 0.09% (-1.49% to 2.61%) in the placebo group (n = 89; P = .25), without between-group difference (P = .12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17% [-.82% to 2.90%]; P = .004) and ≥20 ng/mL (0.93% [-.26% to 2.15%]; P = .033). Conclusions: For youth taking TDF-cART, LSBMD increased through 48 weeks with VITD3 plus multivitamin, but not with placebo plus multivitamin, independent of baseline vitamin D status. Clinical Trials Registration: NCT01751646.

The Feasibility and Acceptability of Using Technology-Based Daily Diaries with HIV-Infected Young Men Who have Sex with Men: A Comparison of Internet and Voice Modalities.

This study delivered a daily diary to 67 HIV-infected men who have sex with men (MSM) between 16 and 24 years old for 66 days to measure HIV-risk behaviors and other psychosocial variables via two diary modalities: internet (accessible via any web-enabled device) and voice (accessible via telephone). Participants were randomized to complete one diary modality for 33 days before switching to the second modality for 33 days. The study was implemented in three urban HIV health care centers in the United States where participants were receiving services. Through diary data and qualitative interview data, we examined the feasibility and acceptability of the dairies and identified barriers and facilitators of dairy compliance. Results show high participant retention in the daily diary (93.4 %) and high compliance for the number of dairies completed (72.4 %). Internet diaries were preferred by 92 % of participants and completed at a significantly higher rate (77.5 %) than voice diaries (67.7 %). Facilitators included opportunities for self-reflection and cathartic sharing, monetary compensation, relationships with study staff, and daily reminders. Barriers included being busy or not having privacy at the time of reminders, forgetting, and falling asleep. Participants also described barriers and facilitators unique to each modality. Overall, both modalities were feasible and acceptable for use with our sample of HIV-infected MSM.

Tenofovir disoproxil fumarate appears to disrupt the relationship of vitamin D and parathyroid hormone.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) increases serum parathyroid hormone (PTH) and 1,25 dihydroxy vitamin D (1,25-(OH)2D), and decreases bone mineral density (BMD). Optimal treatment of TDF-associated BMD loss requires an understanding of the primary cause of these abnormalities. METHODS: Secondary review of data from two studies of TDF use in youth, comparing the relationship of PTH, 25-hydroxy vitamin D (25-OHD) and 1,25-(OH)2D in three groups with varying exposures to TDF: youth without HIV enrolled in a trial of TDF/emtricitabine (FTC) for HIV pre-exposure prophylaxis (PrEP) at baseline (no TDF exposure) and after 12 weeks of TDF (short-term TDF exposure); and youth with HIV treated with TDF-containing combination antiretroviral therapy (cART) for at least 6 months at study entry (long-term TDF exposure). Relationships were evaluated by correlation analyses. RESULTS: Participants ranged in age from 17 to 24 years and >50% were Black/African American. In persons not treated with TDF, PTH had the physiologically appropriate negative correlation with 25-OHD (r=-0.3504, P=0.004). Correlations between PTH and 25-OHD in groups treated with TDF were weaker or absent. With longer term TDF treatment in persons with HIV, 25-OHD and 1,25-(OH)2D had the positive correlation similar to that found in vitamin D deficiency. CONCLUSIONS: TDF changes the relationship of 25-OHD to PTH, suggesting that in persons using TDF for PrEP or cART, a higher than usual target for serum 25-OHD concentration might be needed to reduce PTH and optimize bone health. CLINICAL TRIALS REGISTRATION: NCT01751646 (ATN 109) and NCT01769469 (ATN 117).

Immune Reconstitution but Persistent Activation After 48 Weeks of Antiretroviral Therapy in Youth With Pre-Therapy CD4 >350 in ATN 061.

BACKGROUND: Measures of immune outcomes in youth who initiate combination antiretroviral therapy (cART) early in HIV infection are limited. DESIGN: Adolescent Trials Network 061 examined changes over 48 weeks of cART in T-cell subsets and markers of T-cell and macrophage activation in subjects with pre-therapy CD4 > 350 cells/mm. All subjects had optimal viral suppression from weeks 24 through 48. METHODS: Subjects (n = 48) initiated cART with tenofovir/emtricitabine plus ritonavir-boosted atazanavir. Data were collected at baseline and weeks 12, 24, and 48. Trends were compared to uninfected controls. RESULTS: Significant increases over 48 weeks were noted in all CD4 populations, including total, naive, central memory (CM), and effector memory RO (EM RO) and effector memory RA (EM RA), whereas numbers of CM and EM RO CD8 cells declined significantly. By week 48, CD4 naive cells were similar to controls, whereas CM CD4 cells remained significantly lower and EM RO and EM RA subsets were significantly higher. CD38 and HLA DR expression, both individually and when co-expressed, decreased over 48 weeks of cART on CD8 cells but remained significantly higher than controls at week 48. In contrast, markers of macrophage activation measured by sCD14 and sCD163 in plasma did not change with cART and were significantly higher than controls. CONCLUSIONS: In youth initiating early cART, CD4 cell reconstitution is robust with decreases in CD8 cells. However, CD8 T-cell and macrophage activation persists at higher levels than uninfected controls.

A comparison of network-based strategies for screening at-risk Hispanic/Latino adolescents and young adults for undiagnosed asymptomatic HIV infection.

PURPOSE: Hispanic/Latino adolescents and young adults are disproportionately impacted by the HIV/AIDS epidemic; yet little is known about the best strategies to increase HIV testing in this group. Network-based approaches are feasible and acceptable means for screening at-risk adults for HIV infection, but it is unknown whether these approaches are appropriate for at-risk young Hispanics/Latinos. Thus, we compared an alternative venue-based testing (AVT) strategy with a social and sexual network-based interviewing and HIV testing (SSNIT) strategy. METHODS: All participants were Hispanics/Latinos aged 13-24 years with self-reported HIV risk; they were recruited from 11 cities in the United States and Puerto Rico and completed an audio computer-assisted self-interview and underwent HIV screening. RESULTS: A total of 1,596 participants (94.5% of those approached) were enrolled: 784 (49.1%) through AVT and 812 (50.9%) through SSNIT. HIV infection was identified in three SSNIT (.37%) and four AVT (.51%) participants (p = .7213). CONCLUSIONS: Despite high levels of HIV risk, a low prevalence of HIV infection was identified with no differences by recruitment strategy. We found overwhelming support for the acceptability and feasibility of AVT and SSNIT for engaging and screening at-risk young Hispanics/Latinos. Further research is needed to better understand how to strategically implement such strategies to improve identification of undiagnosed HIV infection.