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Original article

Vitamin D supplementation decreases immune activation and exhaustion in HIV-1-infected youth

Allison Ross Eckard, Mary Ann O’Riordan, Julia C Rosebush, Seungeun Thera Lee, Jakob G Habib, Joshua H Ruff, Danielle Labbato, Julie E Daniels, Monika Uribe-Leitz, Vin Tangpricha, Ann Chahroudi, Grace A McComsey

Corresponding author name: Allison Ross Eckard
Corresponding author e-mail: eckarda@musc.edu

Citation: Antiviral Therapy 2018; 23:315-324
doi: 10.3851/IMP3199

Date accepted: 24 September 2017
Date published online: 10 October 2017

Abstract

Background: Heightened immune activation and exhaustion drive HIV disease progression and comorbidities. Vitamin D has pleiotropic immunomodulatory effects, but little is known about the effects of supplementation in HIV. Our study investigates changes in immune activation and exhaustion markers after 12 months of supplementation in virologically suppressed HIV-infected youth with vitamin D insufficiency.

Methods: This is a randomized, active-control, double-blind trial investigating with three different vitamin D3 doses (18,000 [standard/active-control dose], 60,000 [moderate dose] and 120,000 IU/month [high dose]) in 8–25-year-old HIV-infected youth on combination antiretroviral therapy with baseline serum 25-hydroxyvitamin D (25(OH)D) concentrations ≤30 ng/ml. Only subjects (n=51) who maintained an undetectable HIV-1 RNA over the 12-month study period were included in this analysis.

Results: Baseline serum 25(OH)D concentrations and immune activation/exhaustion markers were not different between groups. By 12 months, 25(OH)D increased significantly within each dosing group with the greatest increase and most sustained concentrations ≥30 ng/ml in the high-dose group. Overall, all measured markers decreased with CD4 activation (CD4+CD38+HLA-DR+), CD8 activation (CD8+CD38+HLA-DR+), CD4 exhaustion (CD4+CD38+HLA-DR+PD1+) and inflammatory monocytes (CD14+CD16+) reaching statistical significance. When analysed separately, there were no significant decreases in the moderate- or standard-dose groups, but CD4 and CD8 activation and inflammatory monocytes decreased significantly in the high-dose group.

Conclusions: Vitamin D supplementation decreased markers of T-cell activation/exhaustion and monocyte activation in HIV-infected youth, with subjects given the highest dose (120,000 IU/month) showing the greatest decreases. These data suggest that high-dose vitamin D supplementation may attenuate immune activation and exhaustion, and serve as adjuvant therapy to antiretroviral therapy in HIV. ClinicalTrials.gov identifier: NCT01523496.

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