Monthly doses of vitamin D increased bone density in HIV-infected youth who were receiving Viread as part of their combination antiretroviral therapy, or cART, according to study results.
Dr Peter L Havens, HIV programme director at Children’s Hospital of Wisconsin, and colleagues compared the effects of a 50,000 IU dose of vitamin D3 taken every 4 weeks for 48 weeks against placebo in adolescent and young adult patients being chronically treated with Viread (tenofovir disoproxil fumarate [TDF], Gilead Sciences).
According to their results, vitamin D supplementation in these patients improved lumbar spine bone mineral density (LSBMD) within 24 weeks and continued through 48 weeks but not hip or total BMD. TDF, which is widely used in cART and HIV pre-exposure prophylaxis, decreases BMD more than other nucleoside reverse transcriptase inhibitors, Havens and colleagues reported.
“We hypothesised that an ‘adolescent-friendly’ monthly dose of vitamin D3 … would increase BMD and decrease PTH” — or parathyroid hormone, which is increased by TDF – “more effectively than a daily multivitamin containing vitamin D3 (400 IU) and calcium in youth with HIV being chronically treated with TDF-containing cART, independent of baseline vitamin D status,” they wrote.
Between October 2012 and May 2016, Havens and colleagues enrolled 214 patients aged 16 to 24 years with behaviorally acquired HIV-1 infection being treated with TDF-containing cART for at least 180 days and with viral loads below 200 copies/mL within 90 days and at the time of screening. The study was conducted at six International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) sites in the US and Puerto Rico.
They randomly assigned the patients to receive either vitamin D3 or placebo and gave participants in each group a multivitamin containing 400 IU of vitamin D3 and 162 mg of calcium to take each day. They collected urine and blood samples at baseline and weeks 12, 24 and 48 hours after a minimum 8-hour fast.
According to Havens and colleagues, multivitamin adherence was poor – just 49% between the two study groups – bit treatment adherence was 100% in both groups. Among the participants who completed 48 weeks, LSBMD increased by 1.15% (95% CI, –0.75 to 2.74) in the group receiving monthly vitamin D3 (n = 99) and 0.09% (95% CI, –1.49 to 2.61; P = 0.25) in the placebo arm (n = 89).
“A strength of this study was enrollment of youth who had [a] viral load of less than 200 copies/mL for 180 days or more on unchanged cART, an index of good adherence to cART. A ‘youth-friendly’ dosing scheme with directly observed monthly vitamin D3/placebo administration was another key component of our study design,” Havens and colleagues wrote.
“The challenges of adherence with the daily multivitamin in our adolescent/young adult cohort suggest that the total vitamin D3 received dose would have been lower with daily dosing, even if a higher daily dose were used. We note that LSBMD was rising through 48 weeks. Longer follow-up perhaps could have shown a greater difference in BMD between the two treatment groups.”
Background: Tenofovir disoproxil fumarate (TDF) decreases bone mineral density (BMD). We hypothesized vitamin D3 (VITD3) would increase BMD in youth receiving TDF.
Methods: Randomized double-blind placebo-controlled trial of directly observed VITD3 vs. placebo every 4 weeks for 48 weeks in youth ages 16-24 years with HIV, viral 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 50,000 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 age 22.0 (21.0, 23.0) years, 84% male, and 74% 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<0.001). From baseline to week 48, LSBMD increased by 1.15 (-0.75, 2.74)% in the VITD3 group (N=99; P<0.001) and 0.09 (-1.49, 2.61)% in the placebo group (N=89; P=0.25), without between-group difference (P=0.12). VITD3 group changes occurred with baseline 25-OHD <20 ng/mL (1.17 (-0.82, 2.90)%; P=0.004) and ≥20 ng/mL (0.93 (-0.26, 2.15)%; P=0.033).
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.
Peter L Havens, Charles B Stephensen, Marta D Van Loan, Gertrud U Schuster, Leslie R Woodhouse, Patricia M Flynn, Catherine M Gordon, Cynthia G Pan, Brandy Rutledge, D Robert Harris, Georgine Price, Alyne Baker, William A Meyer III, Craig M Wilson, Rohan Hazra, Bill G Kapogiannis, Kathleen Mulligan