Short-course zidovudine for perinatal HIV-1 transmission in Bangkok, Thailand: a randomised controlled trial

Summary

Background

Many developing countries have not implemented the AIDS Clinical Trials Group 076 zidovudine regimen for prevention of perinatal HIV-1 transmission because of its complexity and cost. We investigated the safety and efficacy of short-course oral zidovudine administered during late pregnancy and labour.

Methods

In a randomised, double-blind, placebo-controlled trial, HIV-1-infected pregnant women at two Bangkok hospitals were randomly assigned placebo or one zidovudine 300 mg tablet twice daily from 36 weeks' gestation and every 3 h from onset of labour until delivery. Mothers were given infant formula and asked not to breastfeed. The main endpoint was babies' HIV-1-infection status, tested with HIV-1-DNA PCR at birth, 2 months, and 6 months. We measured maternal plasma viral concentrations by RNA PCR.

Findings

Between May, 1996, and December, 1997, 397 women were enrolled; 393 gave birth to 395 live-born babies. Median duration of antenatal treatment was 25 days, and median number of doses during labour was three. 99% of women took at least 90% of scheduled antenatal doses. Adverse events were similar in the study groups. Of 392 babies with at least one PCR test, 55 tested positive: 18 in the zidovudine group and 37 in the placebo group. The estimated transmission risks were 9·4% (95% CI 5·2–13·5) on zidovudine and 18·9% (13·2–24·2) on placebo (p=0·006; efficacy 50% [15·4–70·6]). Between enrolment and delivery, women in the zidovudine group had a mean decrease in viral load of 0·56 log. About 80% of the treatment effect was explained by lowered maternal viral concentrations at delivery.

Interpretation

A short course of twice-daily oral zidovudine was safe and well tolerated and, in the absence of breastfeeding, can lessen the risk for mother-to-child HIV-1 transmission by half. This regimen could prevent many HIV-1 infections during late pregnancy and labour in less-developed countries unable to implement the full 076 regimen.

Introduction

Worldwide, more than 500 000 infants, nearly all born in developing countries, are perinatally infected with HIV-1 each year.¹ A clinical trial in the USA and France (AIDS Clinical Trials Group [ACTG] 076) showed that, in the absence of breastfeeding, zidovudine given orally five times daily to HIV-1-infected pregnant women starting at 14–34 weeks' gestation, intravenously during labour, and orally to babies for 6 weeks, lowered the risk for perinatal HIV-1 transmission by two-thirds.2, 3 This regimen was quickly adopted as standard care in the USA⁴ and western Europe, but, because of its complexity and cost, has not been implemented in most developing countries.

Without intervention, 15–30% of babies born to HIV-1-infected mothers are infected in utero or during labour;5, 6 a further 10–15% are infected through breastfeeding.7, 8, 9 Apart from breastfeeding, most perinatal transmission occurs late in pregnancy or during labour and delivery.10, 11, 12 A short, simple intervention late in pregnancy, if proven safe and effective, would have the potential for much wider implementation than the 076 regimen.

In Thailand, about 20 000 of the 1 million births per year are to HIV-1-infected women. The HIV-1 serostatus of most of these women is determined through antenatal HIV-1 counselling and testing programmes.¹³ HIV-1-positive women are counselled about their infection and discouraged from breastfeeding, but before and during our trial, few were offered zidovudine. The Ministry of Public Health of Thailand and Mahidol University collaborated with the US Centers for Disease Control and Prevention to do a randomised, double-blind, placebo-controlled trial to investigate the safety and efficacy of perinatal short-course oral zidovudine. On the advice of the data and safety monitoring board, and to make this information immediately available, preliminary results of the trial were announced in February, 1998.¹⁴ Here, we describe the definitive results of the trial.