Effect of maternal vitamin D3 supplementation on maternal health, birth outcomes, and infant growth among HIV-infected Tanzanian pregnant women: study protocol for a randomized controlled trial

Abstract Background Vitamin D has significant immunomodulatory effects on both adaptive and innate immune responses. Observational studies indicate that adults infected with HIV with low vitamin D status may be at increased risk of mortality, pulmonary tuberculosis, and HIV disease progression. Growing observational evidence also suggests that low vitamin D status in pregnancy may increase the risk of adverse birth and infant health outcomes. As a result, antiretroviral therapy (ART) adjunct vitamin D3 supplementation may improve the health of HIV-infected pregnant women and their children. Methods/design The Trial of Vitamins-5 (ToV5) is an individually randomized, double-blind, placebo-controlled trial of maternal vitamin D3 (cholecalciferol) supplementation conducted among 2300 HIV-infected pregnant women receiving triple-drug ART under Option B+ in Dar es Salaam, Tanzania. HIV-infected pregnant women of 12–27 weeks gestation are randomized to either: 1) 3000 IU vitamin D3 taken daily from randomization in pregnancy until trial discharge at 12 months postpartum; or 2) a matching placebo regimen. Maternal participants are followed-up at monthly clinic visits during pregnancy, at delivery, and then with their children at monthly postpartum clinic visits. The primary efficacy outcomes of the trial are: 1) maternal HIV disease progression or death; 2) risk of small-for-gestational age (SGA) births; and 3) risk of infant stunting at 1 year of age. The primary safety outcome of the trial is incident maternal hypercalcemia. Secondary outcomes include a range of clinical and biological maternal and child health outcomes. Discussion The ToV5 will provide causal evidence on the effect of vitamin D3 supplementation on HIV progression and death, SGA births, and infant stunting at 1 year of age. The results of the trial are likely generalizable to HIV-infected pregnant women and their children in similar resource-limited settings utilizing the Option B+ approach. Trial registration ClinicalTrials.gov identifier: NCT02305927 . Registered on 29 October 2014.