In order to meet these goals we are proposing a "gold standard" investigation with a randomized, double-blind, placebo-controlled trial. Briefly, we wil enroll 4000 adult men and non-pregnant women who are starting ART within the Management and Development for Health (MDH) President's Emergency Plan for AIDS Relief (PEPFAR) treatment program in Dar-es-Salaam, Tanzania. Individuals who consent for enrollment in the trial will be randomized to receive an oral supplement regimen of one of two groups: (a) vitamin D3 oral supplements containing 50,000 IU taken weekly at clinic visits for 4 weeks (weeks 0, 1, 2, 3) followed by maintenance 2,000 IU oral supplements taken daily at home for the remaining trial duration (week 4 and continued through 1 year) or (b) placebo supplements taken weekly at clinic visits for 4 weeks (weeks 0, 1, 2, 3) followed by placebo oral supplements taken daily at home for the remaining trial duration (week 4 and continued through 1 year). We will then follow study participants for 1 year at monthly clinic and home visits to assess our two primary trial endpoints: (a) death and (b) incident pulmonary tuberculosis. Secondarily, we will also assess the effect of vitamin D3 on (i) CD4 T-cell counts, (ii) incidence of comorbidities and complications associated with HIV and/or ART, (iii) markers of bone health in blood, and (iv) weight gain. Evidence from this randomized trial is urgently needed since ART coverage is rapidly expanding globally and treatment programs are in need of interventions to prolong and improve the quality of life for HIV-infected individuals initiating ART during the first months of treatment.
HIV-infected individuals initiating antiretroviral therapy in sub-Saharan Africa experience very high mortality rates during the first year of HIV treatment. This randomized trial may provide evidence that vitamin D3 supplements prolong and improve the quality of life for these individuals, which may result in adding these supplements to standard HIV care.