Effect of maternal vitamin D 3 supplementation on maternal health, birth outcomes, and infant growth among HIV-infected Tanzanian pregnant women: study protocol for a randomized controlled trial

• Published in: Trials Vol. 18; no. 1; p. 411
• Main Authors: Sudfeld, Christopher R, Manji, Karim P, Duggan, Christopher P, Aboud, Said, Muhihi, Alfa, Sando, David M, Al-Beity, Fadhlun M Alwy, Wang, Molin, Fawzi, Wafaie W
• Format: Journal Article
• Language: English
• Published: England 04.09.2017
• Subjects: Age Factors; Anti-HIV Agents - adverse effects; Anti-HIV Agents - therapeutic use; Birth Weight; Child Development; Cholecalciferol - administration & dosage; Cholecalciferol - adverse effects; Clinical Protocols; Dietary Supplements - adverse effects; Double-Blind Method; Female; HIV Infections - diagnosis; HIV Infections - drug therapy; HIV Infections - mortality; HIV Infections - virology; Humans; Infant; Infant, Newborn; Infant, Small for Gestational Age; Maternal Health; Maternal Health Services; Maternal Mortality; Pregnancy; Pregnancy Complications, Infectious - diagnosis; Pregnancy Complications, Infectious - drug therapy; Pregnancy Complications, Infectious - mortality; Pregnancy Complications, Infectious - virology; Research Design; Tanzania; Time Factors; Treatment Outcome; Vitamin D Deficiency - blood; Vitamin D Deficiency - diagnosis; Vitamin D Deficiency - drug therapy; Vitamin D Deficiency - mortality
• ISSN: 1745-6215
• DOI: 10.1186/s13063-017-2157-3

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 D supplementation may improve the health of HIV-infected pregnant women and their children. The Trial of Vitamins-5 (ToV5) is an individually randomized, double-blind, placebo-controlled trial of maternal vitamin D (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 D 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. The ToV5 will provide causal evidence on the effect of vitamin D 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. ClinicalTrials.gov identifier: NCT02305927 . Registered on 29 October 2014.