Title of article :
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
Abstract :
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 weeksʹ gestation, followed by oral intrapartum dosing and by 7 daysʹ 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% Cl 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% Cl 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