ArticlesIntrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial
Introduction
In 2002, an estimated 800 000 children became infected with HIV-1 through mother-to-child transmission,1 with more than 90% residing in resource-poor countries. In more-developed countries, mother-to-child transmission has been dramatically lowered through use of the Paediatric AIDS Clinical Trials Group (PACTG) 076 zidovudine regimen, given to the mother during pregnancy and labour and to the infant for 6 weeks after birth.2 However, this regimen is too complex and expensive for use in resource-poor countries.
The knowledge that most mother-to-child transmission occurs late in pregnancy or during labour and delivery3, 4 led to shorter zidovudine regimens being given to women a few weeks before and during labour as prophylaxis. This strategy was shown to decrease mother-to-child HIV-1 transmission by 37–38% in breastfeeding populations and by 50% in non-breastfeeding populations.5, 6, 7 However, these regimens, while simpler and less expensive, still remain problematic for implementation in some resource-poor countries, and transmission of HIV-1 postnatally via breast milk remains a problem.8, 9, 10
Because antiretroviral prophylaxis of the neonate during HIV-1 exposure at birth is thought to be an important mechanism for prophylaxis efficacy,11 provision of antiretroviral therapy to the woman at onset of labour and for a short period postnatally to the infant was thought to be sufficient to decrease vertical transmission during the intrapartum and early breastfeeding period. This might offer a less complex and more affordable prophylaxis regimen for HIV-1 infected pregnant women in less-developed countries. The HIVNET 012 study team reported in 199912 that a single-dose intrapartum and neonatal nevirapine regimen significantly decreased the risk of transmission of HIV-1 from mother to child by 47% compared with a short intrapartum/neonatal zidovudine regimen when 87% of babies in the trial had reached age 14–16 weeks. We report on the safety and efficacy of the nevirapine regimen in all study mothers through 6 weeks postpartum and all babies through to 18 months of age.
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Participants and procedure
The HIVNET 012 study protocol was approved by institutional review boards (IRBs) in Uganda and the USA, and informed consent was obtained from all study participants before study enrolment. The study was originally designed to be a 1500 patient randomised placebo-controlled study assessing two intrapartum and neonatal postpartum regimens, one zidovudine and the other nevirapine. However, after demonstration of the efficacy of a short antepartum/intrapartum zidovudine regimen in Thailand7 and
Results
Enrolment began Nov 3, 1997, and ended on April 30, 1999. The last infant was born on June 19, 1999, and the last infant visit was done on Jan 22, 2001. 645 women were enrolled of whom 626 were randomly assigned zidovudine or nevirapine, with 313 in each group; 19 mothers were randomly assigned placebo (figure 1).
Characteristics of women who gave birth in the two treatment groups did not differ significantly at enrolment (table 1). Nine of 75 caesarean sections were listed as elective. 37
Discussion
In our initial report of the results of HIVNET 012, a single dose of nevirapine given to the mother intrapartum and to the baby postnatally lowered the risk of perinatal transmission by 47% compared with an intrapartum and 1 week postnatal regimen of zidovudine.12 The current report is an 18-month follow-up and indicates persistent efficacy of the single-dose nevirapine regimen in breastfeeding babies. The nevirapine regimen achieved an absolute reduction of 8·2% in HIV-1 transmission at age
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