Efficacy of three short-course regimens of zidovudine and lamivudine in preventing early and late transmission of HIV-1 from mother to child in Tanzania, South Africa, and Uganda (Petra study): a randomised, double-blind, placebo-controlled trial.

BACKGROUND

Large reductions in transmission of HIV-1 from mother to child have been achieved in more-developed countries due to the use of antiretrovirals. Short-course regimens, suitable for resource-poor countries, have also been shown to significantly reduce peripartum HIV-1 transmission. We assessed the efficacy of short-course regimens with zidovudine and lamivudine in a predominantly breastfeeding population.

METHODS

We did a randomised, double-blind, placebo-controlled trial in South Africa, Uganda, and Tanzania. Between June, 1996, and January, 2000, HIV-1-infected mothers were randomised to one of four regimens: A, zidovudine plus lamivudine starting at 36 weeks' gestation, followed by oral intrapartum dosing and by 7 days' postpartum dosing of mothers and infants; B, as regimen A, but without the prepartum component; C, intrapartum zidovudine and lamivudine only; or placebo. From Feb 18, 1998, onward, women were only randomised to one of the active treatment groups. Primary outcomes were HIV-1 infection and child mortality at week 6 and month 18 after birth. Analysis was by intention to treat of those randomised before Feb 18, 1998.

FINDINGS

1797 HIV-1-infected women were identified. Week 6 HIV-1 transmission rates were 5.7% for group A, 8.9% for group B, 14.2% for group C, and 15.3% for the placebo group. Respective relative risks for HIV-1 transmission in the treatment groups compared with placebo were 0.37 (95% CI 0.21-0.65), 0.58 (0.36-0.94), and 0.93 (0.62-1.40). For the combined endpoint of HIV-1 infection and infant mortality at week 6 rates were 7.0%, 11.6%, 17.5%, and 18.1%, respectively, with relative risks of 0.39 (0.24-0.64), 0.64 (0.42-0.97), and 0.97 (0.68-1.38). 1081 (74%) of the women analysed initiated breastfeeding. Based on an interval-censored survival analysis, HIV-1 infection rates at month 18 were 15% (95% CI 9-23), 18% (12-26), 20% (13-30) and 22% (16-30), respectively.

INTERPRETATION

Although at week 6 after birth, regimens A and B were effective in reducing HIV-1 transmission, benefits have diminished considerably after 18 months of follow-up. Introduction of short-course regimens to prevent mother-to-child transmission of HIV-1 in less-developed countries should be accompanied by interventions to minimise the risk of subsequent transmission via breastfeeding.