Maternal or Infant Antiretroviral Drugs to Reduce HIV-1 Transmission

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

From the University of North Carolina Project, Lilongwe, Malawi (C.S.C., D.K., M.C.H., F.M., G.T., D.D.K., Z.K., A.S., I.A.M., M.C., D.S.S.); the University of North Carolina (M.G.H., M.C.H., D.D.K., I.F.H., S.A.F., P.K., I.A.M., C.M.H.) and Principia (R.J.K.) — both in Chapel Hill; and the Centers for Disease Control and Prevention, Atlanta (D.J.J., A.P.K., Y.I.A., S.R.E., J.B.W.).
¹Members of the Breastfeeding, Antiretrovirals, and Nutrition (BAN) study group are listed in the Appendix.

The findings and conclusions of this study are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.

Supported by grants from the Prevention Research Centers Special Interest Project of the Centers for Disease Control and Prevention (SIP 13-01 U48-CCU409660-09 and SIP 26-04 U48-DP000059-01), the National Institute of Allergy and Infectious Diseases, the University of North Carolina Center for AIDS Research (P30-AI50410), the NIH Fogarty AIDS International Training and Research Program (DHHS/NIH/FIC 2-D43 Tw01039-06), Abbott Laboratories, GlaxoSmithKline, Boehringer Ingelheim, Roche Pharmaceuticals, Bristol-Myers Squibb, the Elizabeth Glaser Pediatric AIDS Foundation, the United Nations Children's Fund, the World Food Program, the Malawi Ministry of Health and Population, Johnson & Johnson, and the U.S. Agency for International Development.

Dr. Van der Horst reports receiving grant support from Abbott Laboratories and GlaxoSmithKline; and Dr. Hosseinipour, receiving a lecture fee from Abbott Laboratories. No other potential conflict of interest relevant to this article was reported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

We thank all the women and their infants who participated in this study.

New England Journal of Medicine 362(24):p 2271-2281, June 17, 2010. | DOI: 10.1056/NEJMoa0911486

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.)