Vitamin D3 supplementation during pregnancy and lactation for women living with HIV in Tanzania: A randomized controlled trial

Randomized, placebo-controlled trial among pregnant women living with HIV in urban Dar es Salaam, Tanzania, recruited from 5 public antenatal care clinics and followed through 12 months postpartum. In the Vitamin D3 arm, 1,148 participants were randomized in a 1:1 design against placebo; all women were adults on antiretroviral therapy.

Daily oral vitamin D3 (cholecalciferol) 3,000 IU was started at randomization in the second trimester and continued through pregnancy, lactation, and until 1 year postpartum. The active regimen was compared with a matching daily oral placebo.

Vitamin D3 supplementation did not improve the main maternal or infant outcomes. Maternal HIV progression or death occurred in 166/1,148 vs 141/1,151 women (hazard ratio 1.21, 95% CI 0.97 to 1.52; p = 0.09), small-for-gestational-age birth was 21.4% vs 21.6% (relative risk 1.03, 0.87 to 1.22; p = 0.70), and infant stunting at 1 year was 46.9% vs 47.4% (relative risk 1.00, 0.92 to 1.10; p = 0.95). Vitamin D3 increased maternal and infant 25(OH)D concentrations and did not increase maternal hypercalcemia. Secondary findings suggested possible increases in preterm birth (26.2% vs 22.1%; relative risk 1.17, 1.00 to 1.36; p = 0.04) and a shorter gestation by 0.36 weeks, but these signals may be due to chance.

The trial showed no benefit on the prespecified primary outcomes, and some secondary findings were based on post hoc analyses, increasing the likelihood of chance findings. Interpretation is also limited by multiple comparisons and by generalizability to women living with HIV on antiretroviral therapy in urban Tanzania rather than broader populations.