Randomized trial of vitamin supplements in relation to vertical transmission of HIV-1 in Tanzania.

BACKGROUND: Observational studies suggest that poor nutritional status among HIV-infected pregnant women is associated with a higher risk of vertical transmission of HIV. METHODS: We randomized 1083 pregnant women infected with HIV-1 in a double-blind, placebo-controlled trial to examine the effects of supplements of vitamin A and/or multivitamins (excluding vitamin A) using a 2-x-2 factorial design. We report the effects of the supplements on HIV infection defined using polymerase chain reaction (PCR), or death up to 6 weeks postpartum. RESULTS: Of babies in the multivitamin arm 38, (10.1%) were HIV-positive at birth compared with 24 (6.6%) in the no-multivitamin arm (relative risk [RR] = 1.54; 95% CI, 0.94-2.51; p = .08). Of babies born to mothers in the vitamin A arm, 38 (10.0%) were HIV-positive at birth compared with 24 (6.7%) in the no-vitamin A arm (RR, 1.49; 95% CI, 0.91-2.43; p = 0.11). Neither multivitamins nor vitamin A had an effect on HIV status at 6 weeks among those who were HIV-negative at birth (RR = 1.04; 95% CI, 0.65-1.66; p = 0.88) and (RR = 1.30; 95% CI, 0.80-2.09; p = .29, respectively). Similarly, neither supplement was associated with being either HIV-infected or dead at birth (RR, 0.98; 95% CI, 0.76-1.27; p = .89 and RR, 1.01; 95% CI, 0.78-1.31; p = .95, respectively. A beneficial effect of multivitamins on birth weight was limited to babies who were HIV-negative at birth; babies in the multivitamin arm weighed +94 g more compared with those in the no-multivitamin arm (p = .02). Among babies who were HIV-positive at birth, the corresponding difference was -31 g (p = .82). CONCLUSIONS: Vitamin A and multivitamins did not affect the risk of vertical transmission of HIV in utero nor during the intrapartum and early breastfeeding periods. Multivitamins resulted in a significant improvement in birth weight of babies who were HIV-negative at birth but had no effect among those who were HIV-positive. The effect of vitamin supplements on HIV transmission through breastfeeding and on clinical progression of HIV disease is yet to be ascertained.

Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania.

BACKGROUND: In HIV-1-infected women, poor micronutrient status has been associated with faster progression of HIV-1 disease and adverse birth outcomes. We assessed the effects of vitamin A and multivitamins on birth outcomes in such women. METHODS: In Tanzania, 1075 HIV-1-infected pregnant women at between 12 and 27 weeks' gestation received placebo (n=267), vitamin A (n=269), multivitamins excluding vitamin A (n=269), or multivitamins including vitamin A (n=270) in a randomised, double-blind, placebo-controlled trial with a 2x2 factorial design. We measured the effects of multivitamins and vitamin A on birth outcomes and counts of T lymphocyte subsets. We did analyses by intention to treat. RESULTS: 30 fetal deaths occurred among women assigned multivitamins compared with 49 among those not on multivitamins (relative risk 0.61 [95% CI 0.39-0.94] p=0.02). Multivitamin supplementation decreased the risk of low birthweight (<2500 g) by 44% (0.56 [0.38-0.82] p=0.003), severe preterm birth (<34 weeks of gestation) by 39% (0.61 [0.38-0.96] p=0.03), and small size for gestational age at birth by 43% (0.57 [0.39-0.82] p=0.002). Vitamin A supplementation had no significant effect on these variables. Multivitamins, but not vitamin A, resulted in a significant increase in CD4, CD8, and CD3 counts. INTERPRETATION: Multivitamin supplementation is a low-cost way of substantially decreasing adverse pregnancy outcomes and increasing T-cell counts in HIV-1-infected women. The clinical relevance of our findings for vertical transmission and clinical progression of HIV-1 disease is yet to be ascertained.

PIP: Poor micronutrient status has been associated, in HIV-positive women, with faster progression of HIV disease and adverse birth outcomes. This randomized, double-blind, placebo-controlled study assessed the effects of vitamin A and multivitamins on birth outcomes in 1075 HIV-positive pregnant women at 12-27 weeks' gestation from Dar es Salaam, Tanzania. There were no differences in baseline plasma vitamin concentrations between groups. 267 women received a placebo, 269 were given vitamin A, 269 were administered a multivitamin excluding vitamin A, and 270 received a multivitamin including vitamin A. There were 30 fetal deaths in the group of women who received multivitamins (with and without vitamin A) compared with 49 among those not given multivitamins (relative risk (RR), 0.61; 95% confidence interval (CI), 0.39-0.94). Multivitamin supplementation decreased the risk of low birth weight (2500 g) by 44% (RR, 0.56; 95% CI, 0.38-0.82), of preterm birth (prior to 34 weeks gestation) by 39% (RR, 0.61; 95% CI, 0.38-0.96), and of small size for gestational age at birth by 43% (RR, 0.57; 95% CI, 0.39-0.82). Vitamin A had no significant effect on these variables. Multivitamins, but not vitamin A, were associated with significant increases in CD4, CD8, and CD3 counts. The clinical relevance of multivitamin supplementation for vertical transmission of HIV and the progression of disease remain unknown. However, these results indicate such supplementation is a low-cost means of substantially decreasing adverse pregnancy outcomes and increasing T cell counts in HIV-infected women. The observed beneficial effects of multivitamins on birth outcomes may have been mediated through improved maternal immune status.