Trial of Vitamin D in HIV Progression (TOV4)

The purpose of this study is to determine the efficacy and safety of vitamin D3 (cholecalciferol) supplementation on HIV progression and incidence of pulmonary tuberculosis among HIV-positive Tanzanian adult men and women initiating highly active antiretroviral therapy (HAART).

HIV-infected adults initiating antiretroviral therapy in resource-limited settings experience high mortality, pulmonary tuberculosis, and other comorbidity rates during the first year of HIV treatment. Observational studies have shown low vitamin D is a risk factor for HIV progression and incidence of pulmonary tuberculosis among adults initiating HAART; however, whether this relationship is causal and if vitamin D supplementation starting at HAART initiation can improve health outcomes has not been determined. This study is a randomized, double-blind, placebo-controlled trial conducted to examine the effect of vitamin D3 supplementation on morality and pulmonary tuberculosis for adults initiating HAART. Participants are HIV-positive Tanzanian men and women aged 18 years and older, who are initiating HAART at the time of randomization whose baseline 25-hydroxyvitamin D (25(OH)D) concentration is <30ng/mL. Eligible individuals are randomized to receive a) a vitamin D3 regimen consisting 50,000 IU of vitamin D3 taken orally once per week for 4 weeks (weeks 0, 1, 2, 3) followed by 2,000 IU of vitamin D3 supplements taken orally once per day starting at 4 weeks until study discharge at 12 months or b) placebo pills taken once weekly for 4 weeks (weeks 0, 1, 2, 3) followed by placebo pills taken daily starting at 4 weeks until study discharge. Participants will be followed for 12 months after ART initiation.

Supplements containing 50,000 IU of vitamin D3 (cholecalciferol) taken orally once per week for 4 weeks (weeks 0, 1, 2, 3) followed by 2,000 IU of vitamin D3 (cholecalciferol) supplements taken orally once per day starting at 4 weeks until study discharge at 12 months

Placebo pills taken once weekly for 4 weeks (weeks 0, 1, 2, 3) followed by placebo pills taken orally once per day starting at 4 weeks until study discharge at 12 months

Inclusion Criteria: HIV-positive Men or Women 18 Years of Age or older Initiating HAART at time of randomization 25(OH)D concentration <30 ng/mL at HAART initiation Exclusion Criteria: Pregnant Women Enrolled in another micronutrient trial

Sudfeld CR, Mugusi F, Aboud S, Nagu TJ, Wang M, Fawzi WW. Efficacy of vitamin D3 supplementation in reducing incidence of pulmonary tuberculosis and mortality among HIV-infected Tanzanian adults initiating antiretroviral therapy: study protocol for a randomized controlled trial. Trials. 2017 Feb 10;18(1):66. doi: 10.1186/s13063-017-1819-5.

Muhihi A, Fawzi WW, Aboud S, Nagu TJ, Ulenga N, Wang M, Mugusi F, Sudfeld CR. Cholecalciferol Supplementation Does Not Affect the Risk of HIV Progression, Viral Suppression, Comorbidities, Weight Loss, and Depression among Tanzanian Adults Initiating Antiretroviral Therapy: Secondary Outcomes of a Randomized Trial. J Nutr. 2022 Aug 9;152(8):1983-1990. doi: 10.1093/jn/nxac096.

Sudfeld CR, Mugusi F, Muhihi A, Aboud S, Nagu TJ, Ulenga N, Hong B, Wang M, Fawzi WW. Efficacy of vitamin D3 supplementation for the prevention of pulmonary tuberculosis and mortality in HIV: a randomised, double-blind, placebo-controlled trial. Lancet HIV. 2020 Jul;7(7):e463-e471. doi: 10.1016/S2352-3018(20)30108-9.