ArticlesShort postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial
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.
Section snippets
Participants
The NVAZ study was done in six clinics in the Blantyre area of Malawi between April, 2000, and January, 2002. We assessed women of unknown HIV status who presented for delivery. Women in advanced labour (cervical dilatation >6 cm, strong and regular uterine contractions, second stage of labour, or an estimate that delivery would occur within 2 h of admission), and those delivering immediately after arrival and before vaginal examination was done could not receive intrapartum nevirapine. Time
Results
From April, 2000, to January, 2002, we screened 12 355 women for participation in the study (figure). Of these, 11 236 did not meet eligibility requirements; most were HIV negative. A total of 1119 women were enrolled, and 562 babies were randomly allocated nevirapine and zidovudine and 557 were allocated nevirapine only. Women were enrolled on the basis of results of a rapid HIV test done in the postnatal ward (confirmatory HIV ELISA tests were not available until later). 13 women (seven who
Discussion
We assessed the efficacies of short postexposure prophylaxis antiretroviral regimens in babies of women who presented late for delivery in Malawi. In babies born to mothers who did not receive intrapartum nevirapine, a combination of one oral dose of nevirapine and zidovudine, orally twice daily for 7 days, given immediately after birth was efficacious in lowering mother-to-child transmission of HIV at 6–8 weeks compared with a regimen of nevirapine only. We estimate that the nevirapine and
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