ArticlesExtended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials
Introduction
Prevention of mother-to-child transmission of HIV can be achieved through administration of highly active antiretroviral therapy (HAART) to pregnant HIV-infected women.1 In settings where access to HAART is limited, other effective strategies have been developed, including administration of single-dose nevirapine to HIV-infected mothers in labour and to their infants within 72 hours of birth.2, 3 However, breastfeeding continues to pose a significant risk of HIV transmission to infants born to HIV-infected mothers, accounting for about 150 000 infant infections per year, mainly in low-income settings.4 HIV-infected mothers in communities where safe and affordable infant feeding alternatives are available are advised not to breastfeed their infants.5 In resource-limited settings, infants of HIV-infected mothers who are not breastfed are at very high risk for mortality and morbidity, which can exceed the risk associated with HIV infection itself.6, 7 As a result, UNICEF/WHO recommendations advise that infants born to HIV-infected mothers who do not have access to acceptable, feasible, affordable, sustainable, and safe replacement feeding should be exclusively breastfed for at least 6 months.5 Since more than 80% of all HIV-infected mothers are in sub-Saharan Africa and Asia,4 where access to safe and nutritionally adequate alternatives to breast milk are limited, there is a critical need to identify strategies to prevent HIV transmission by breastfeeding. Provision of antiretroviral medications to infants exposed to HIV by breastfeeding is one potential prevention strategy in these settings. A significant risk for breast milk transmission of HIV occurs within the first 6 weeks post partum.8, 9 Therefore, targeting interventions to this early breastfeeding period could be particularly important.
This combined analysis of data from three separate, but coordinated, randomised clinical trials in Ethiopia, India, and Uganda provides an opportunity to determine whether giving low-dose nevirapine to breastfed infants born to HIV-infected mothers in the first 6 weeks of life could prevent more early post-partum HIV transmission than the standard single-dose nevirapine regimen given to mothers and infants alone.
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Participants
Pregnant women who presented to antenatal and delivery facilities in Addis Ababa, Ethiopia, Pune, India, and Kampala, Uganda, who were identified as HIV-infected, were offered the local standard of care for prevention of mother-to-child transmission of HIV and provided infant feeding counselling, consistent with WHO/UNICEF guidelines. Women who indicated an intention to breastfeed their infants and provided informed consent were eligible for study enrolment. Written consent was obtained where
Results
Figure 1 shows the trial profile. 2024 liveborn infants with at least one specimen tested before 6 months of age were randomised (1047 infants in the single-dose group and 977 infants in the extended-dose group). 137 infants were excluded from the modified intention-to-treat population: 36 did not have birth specimens available for testing, eight were of indeterminate HIV infection status at birth or 6 months, and 93 were found to be infected at birth. Inverse variance-weighted HIV infection
Discussion
The results of this study indicate that, among breastfeeding infants who were HIV uninfected at birth, extended use of oral nevirapine 5 mg/day did not significantly reduce the risk of infection with HIV at 6 months compared with single-dose nevirapine. This lack of significance could have been due to a loss of statistical power from underlying HIV transmission rates that were lower than those used for our sample size calculation, particularly in the control group (estimated rate of 18·0% vs
References (32)
- et al.
Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: HIVNET 012 randomised trial
Lancet
(1999) - et al.
Replacement fed infants born to human immunodeficiency virus-infected mothers in India have a high early post-partum rate of hospitalization
J Nutr
(2003) - et al.
Mother-to-child transmission of HIV-1 infection during exclusive breastfeeding in the first 6 months of life: an intervention cohort study
Lancet
(2007) - et al.
Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18 months follow-up of the HIVNET 012 randomised trial
Lancet
(2003) - et al.
Safety profile of nevirapine, a nonucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus infection
Clin Ther
(1998) - et al.
Short postexposure prophylaxis in newborn babies to reduce mother-to-child transmission of HIV-1: NVAZ randomised clinical trial
Lancet
(2003) Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1 infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States
- et al.
Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection
Cochrane Database Syst Rev
(2007) 2006 report on the global AIDS epidemic
Consensus statement. WHO HIV and Infant Feeding Technical Consultation Held on behalf of the Inter-agency Task Team (IATT) on prevention of HIV infections in pregnant women, mothers and their infants
HIV transmission through breastfeeding: a study in Malawi
JAMA
Effect of breastfeeding and formula feeding on transmission of HIV-1: a randomized clinical trial
JAMA
A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1 infected pregnant Ugandan women and their neonates (HIVNET 006)
AIDS
Diagnosis of HIV-1 infection in children younger than 18 months in the United States
Pediatrics
Sample size determination for case-control studies and the comparison of stratified and unstratified analyses
Biometrics
Modern epidemiology
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