Nevirapine results quickly put into practice.

A randomized controlled trial conducted in the late 1990s in Kampala, Uganda, (1) helped to create--at an unprecedented pace--a standard for preventing mother-to-child transmission of HIV in the developing world.

The rate of HIV transmission from mother to child in developing countries is estimated to be as high as 43 percent, (2) with most cases occurring late in pregnancy or during labor and delivery. (3) Recognizing the urgent need to reduce these transmission rates, the international HIV Network for Prevention Trials (HIVNET), established by the National Institute of Allergy and Infectious Diseases (NIAID) in the United States, supported the Ugandan trial. As trial coordinator, FHI collaborated with Makerere University in Kampala, Johns Hopkins University in Baltimore, MD, USA, the University of Washington and the Fred Hutchinson Cancer Research Center in Seattle, WA, USA, and several other partners to test the safety and efficacy of the antiretroviral nevirapine versus a specific regimen of the antiretroviral zidovudine (AZT) for preventing transmission from more than 600 pregnant, HIV-infected women to their infants.

Half of the women in the trial were randomly assigned to receive a single dose of nevirapine at the onset of labor, and their infants received a single dose within 72 hours of birth. The other half of the women were assigned to receive doses of AZT at the onset of labor and every three hours until delivery, and their infants received twice-daily doses of AZT for a week after birth. Results showed that nevirapine was 47 percent more effective than AZT: Fourteen to 16 weeks after delivery, only 13 percent of infants given nevirapine were infected with HIV, compared with 25 percent of infants given AZT.

The strength of the study findings and their potential for a substantial public health impact--uniquely coupled with other facilitating factors such as political interest and support, strong advocacy, and nevirapine's low cost, readily available supplies, and relatively easy storage and administration--helped propel the findings into practice. In July 1999, interim data were reviewed by the data and safety monitoring board overseeing the study, and the findings were immediately released to the public. In August 1999, nevirapine was included on the agenda of an international working group meeting on mother-to-child transmission of HIV, held by the Joint United Nations Programme on HIV/AIDS (UNAIDS) to develop recommendations for using new antiretroviral regimens. In September 1999, the findings were formally published. By the next year, the Elizabeth Glaser Pediatric AIDS Foundation had raised more than U.S. $15 million to establish a "Call to Action" project to support implementation of the findings.

Approximately 50 nevirapine programs have now been established in at least 17 countries,and this simple regimen is now the standard for preventing mother-to-child transmission of HIV in many parts of the developing world. Recent research has confirmed the safety and effectiveness of nevirapine, (4) which may help governments in other countries adopt the practice.

"We estimate that more than 250,000 women have been offered voluntary HIV counseling and testing through Call to Action programs established by the Elizabeth Glaser Pediatric AIDS Foundation, more than 27,000 HIV-infected women have been identified, and at least half of these women have received nevirapine," says Dr. Willard Cates Jr., president of FHI's institute for Family Health."Thousands of infants have been spared HIV infection as a result of this finding and its utilization."

References

(1) Guay LA, Musoke P, Fleming T, 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; 354(9181):795-802.

(2) The Working Group on Mother-to-Child Transmission of HIV. Rates of mother-to-child transmission of HIV-1 in Africa, America, and Europe: results from 13 perinatal studies. J Acquir Immune Defic Syndr Hum Retrovirol 1995;8(5):506-10.

(3) Rouzioux C, Costagliola D, Burgard M, et al. Estimated timing of mother-to-child human immunodeficiency virus type I (HIV-1) transmission by use era of a Markov model. The HIV Infection in Newborns French Collaborative Study Group. Am J Epidemiol 1995;142(12): 1330-37; Bertolli J, St. Louis ME, Simonds RJ, et al. Estimating the timing of mother-to-child transmission of human immunodeficiency virus in a breast-feeding population in Kinshasa, Zaire. J Infect Dis 1996;174(4):722-26.

(4) Moodley D, Moodley J, Coovadia H, et al. A multicenter randomized controlled trial of nevirapine versus a combination of zidovudine and lamivudine to reduce intrapartum and early postpartum mother-to-child transmission of human immunodeficiency virus type 1. J Infect Dis 2003;187(5):725-35.