Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission

Volume 362:2271-2281 June 17, 2010 Number 24

Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission

Charles S. Chasela, Ph.D., Michael G. Hudgens, Ph.D., Denise J. Jamieson, M.D., M.P.H., Dumbani Kayira, M.B., B.S., Mina C. Hosseinipour, M.D., M.P.H., Athena P. Kourtis, M.D., Ph.D., Francis Martinson, M.B., Ch.B., Ph.D., Gerald Tegha, B.Sc., Rodney J. Knight, Ph.D., Yusuf I. Ahmed, B.M., Deborah D. Kamwendo, M.Sc., Irving F. Hoffman, P.A., M.P.H., Sascha R. Ellington, M.S.P.H., Zebrone Kacheche, B.Sc., Alice Soko, R.N., Jeffrey B. Wiener, Ph.D., Susan A. Fiscus, Ph.D., Peter Kazembe, M.B., Ch.B., Innocent A. Mofolo, M.Sc., Maggie Chigwenembe, R.N., Dorothy S. Sichali, B.Sc., Charles M. van der Horst, M.D., for the BAN Study Group


ABSTRACT

Background We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 (HIV-1) in Malawi.

Methods We randomly assigned 2369 HIV-1–positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the Kaplan–Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1–negative 2 weeks after birth. Rates were compared with the use of the log-rank test.

Results Among mother–infant pairs, 5.0% of infants were HIV-1–positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P=0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P=0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction.

Conclusions The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736 [ClinicalTrials.gov] .)



Approximately 200,000 infants worldwide become infected annually with human immunodeficiency virus type 1 (HIV-1) through breast-feeding.1,2 Without treatment, half of these infants will die before their second birthday.3 Although formula feeding decreases the risk of postnatal HIV transmission, it is associated with an increased rate of early death.4,5 Thus, exclusive breast-feeding is recommended by the World Health Organization (WHO) for infants of HIV-1–positive women for the first 6 months of life in resource-limited settings.6
The use of antiretroviral drugs during pregnancy, labor, and delivery effectively reduces intrauterine and intrapartum HIV-1 transmission.7,8 However, without prophylaxis, an additional 9% of HIV-1–negative infants who are born to HIV-1–positive mothers will become infected after 18 months of breast-feeding.9 Several observational or uncontrolled studies that have examined the use of either an extended maternal triple-drug regimen or extended infant prophylaxis have suggested that these interventions reduce postnatal HIV-1 transmission.4,10,11,12,13,14 No studies to date have compared infant and maternal interventions. Two clinical trials have shown that infant prophylaxis with daily nevirapine for either 6 weeks or 14 weeks during breast-feeding reduced early postnatal HIV transmission.15,16

The Breastfeeding, Antiretrovirals, and Nutrition (BAN) study was a randomized, controlled trial evaluating the safety and efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine administered during 28 weeks of breast-feeding in reducing postpartum HIV transmission.

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