Efficacy of vitamin D supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial.

BACKGROUND

HIV-infected adults initiating antiretroviral therapy (ART) in sub-Saharan Africa continue to experience high rates of morbidity and mortality during the initial months of treatment. Observational studies in high-income and resource-limited settings indicate that HIV-infected adults with low vitamin D levels may be at increased risk of mortality, HIV disease progression, and incidence of pulmonary tuberculosis (TB). As a result, vitamin D supplementation may improve survival and treatment outcomes for HIV-infected adults initiating ART.

METHODS/DESIGN: The Trial of Vitamins-4 (ToV4) is an individually randomized, double-blind, placebo-controlled trial of vitamin D (cholecalciferol) supplementation conducted among 4000 HIV-infected adults with low vitamin D levels [25-hydroxyvitamin D (25(OH)D) <30 ng/mL] initiating ART in Dar es Salaam, Tanzania. The two primary aims of the trial are to determine the effect of a vitamin D supplementation regimen on incidence of (1) mortality and (2) pulmonary TB as compared to a matching placebo regimen. The primary safety outcome of the study is incident hypercalcemia. The investigational vitamin D regimen consists of oral supplements containing 50,000 IU vitamin D taken under direct observation at randomization and once a week for 3 weeks (four doses) followed by daily oral supplements containing 2000 IU vitamin D taken at home from the fourth week until trial discharge at 1 year post ART initiation. Trial participants are followed up at weekly clinic visits during the first month of ART and at monthly clinic visits thereafter until trial discharge at 1 year post ART initiation. Secondary aims of the trial are to examine the effect of the vitamin D regimen on CD4 T cell reconstitution, incidence of non-TB comorbidities, body mass index (BMI), depression and anxiety, physical activity, bone health, and immunologic biomarkers.

DISCUSSION

The ToV4 will provide causal evidence on the effect of vitamin D supplementation on incidence of pulmonary TB and mortality among HIV-infected Tanzanian adults initiating ART. The trial will also give insight to whether vitamin D supplementation trials for the prevention of pulmonary TB should be pursued in HIV-uninfected populations.

TRIAL REGISTRATION

ClinicalTrials.gov, NCT01798680 . Registered on 21 February 2013.