Short postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial

Summary

Background

In sub-Saharan Africa, most women present late for delivery with unknown HIV status, which limits the use of intrapartum nevirapine to prevent mother-to-child transmission of HIV. We aimed to determine whether post-exposure prophylaxis of nevirapine plus zidovudine given to babies only reduced transmission of HIV more than did a regimen of nevirapine alone.

Methods

We randomly assigned 1119 babies of Malawian women with HIV-1 who presented late (ie, within 2 h of expected delivery) to either nevirapine alone or nevirapine and zidovudine. Both drugs were given immediately after birth: one dose of nevirapine (2 mg/kg weight) was given as a single dose; babies in the nevirapine plus zidovudine group also received zidovudine twice daily for 1 week (4 mg/kg weight). Infant HIV infection was determined at birth and at 6–8 weeks. Primary outcome was HIV infection in babies at 6–8 weeks in those not infected at birth. Analysis was by intention to treat.

Findings

The overall rate of mother-to-child transmission at 6–8 weeks was 15·3% in 484 babies who received nevirapine and zidovudine and 20·9% in 468 babies who received nevirapine only (p=0·03). At 6–8 weeks, in babies who were HIV negative at birth, 34 (7·7%) babies who had nevirapine and zidovudine and 51 (12·1%) who received nevirapine only were infected (p=0·03)—a protective efficacy of 36%. This finding remained after controlling for maternal viral load and other factors at baseline. Adverse events were mild and of similar frequency in the two groups.

Interpretation

Postexposure prophylaxis can offer protection against HIV infection to babies of women who missed opportunities to be counselled and tested before or during pregnancy. The nevirapine and zidovudine regimen is safe and easy to implement.

Introduction

Zidovudine and nevirapine have been shown to reduce mother-to-cild transmission of HIV in breastfeeding women in Africa. In Ivory Coast, zidovudine started at 36 weeks' gestation and continued during delivery reduced mother-to-child transmission from 24·9% to 15·7%.¹ Another regimen that included postnatal maternal zidovudine reduced transmission of the disease from 21·8% to 15·1% in Ivory Coast and Burkina Faso.² In the Petra study,³ several zidovudine and lamivudine (3TC) regimens were assessed in a multicentre trial in Uganda, Tanzania, and South Africa. Intrapartum zidovudine and lamivudine plus postpartum zidovudine and lamivudine to mother and baby reduced mother-to-child transmission to 8·9%, compared with 15·3% in placebo recipients.³ In the HIVNET 012 study⁴ in Uganda, one dose of nevirapine to the woman during delivery and one dose of the same drug to the baby within the first 72 h of birth decreased infant HIV infection at age 6–8 weeks from 20·0% in the zidovudine comparison group to 11·8% in the nevirapine group.⁵

Despite the simplicity of the HIVNET 012 regimen, some constraints might limit its wider implementation. Counselling and HIV testing for pregnant women in antenatal clinics are often not available. Most women present to the labour ward only hours before delivery, unaware of their HIV status, and with little time to counsel, do an HIV test, and if infected, to administer nevirapine before delivery. Furthermore, protective concentrations of nevirapine in cord blood are achieved only when intrapartum nevirapine is given 2 h or more before delivery.⁶ In view of these difficulties, another approach to prevent mother-to-child transmission of HIV in women with unknown HIV status at time of delivery is to give HIV counselling and tests to women after they recover from delivery, and to administer antiretroviral drugs to babies as a postexposure prophylaxis. Although HIV counselling and testing immediately before or after delivery are not ideal, the urgency of protecting the baby against HIV infection should be considered.

Results from studies in animals and occupational exposure studies lend support to the rationale for postexposure prophylaxis,7, 8 as do data that show that perinatal HIV transmission is lowered when newborns received zidovudine prophylaxis in the first 48 h of life.⁹ Our clinical trial (the NVP/AZT trial—hence NVAZ) was in babies born to women who arrived too late to the labour room to receive HIV counselling, testing, and administration of intrapartum nevirapine before delivery. We aimed to determine the efficacy of a short neonatal-only postexposure prophylaxis of nevirapine and zidovudine, compared with nevirapine administered immediately after birth in reducing mother-to-child transmission of HIV-1.