In their study of more than 600 women in Uganda, giving one dose of nevirapine, a common HIV-fighting drug, to HIV-positive mothers during labor, and one dose to their newborns, reduced transmission by 41 percent, compared to a multi-dose regimen of the drug zidovudine, commonly called AZT. Africa is home to roughly 30 million HIV-positive people, about 3 million of whom are pregnant women. The report documents all the babies' health at 6 to 8 weeks and at 18 months.
"This use of nevirapine, if widely implemented, has the potential to prevent several hundred thousand new infections every year," says J. Brooks Jackson, M.D., director of pathology at the Johns Hopkins School of Medicine. "This regimen is extremely simple, safe and inexpensive, but access to HIV testing and counseling remains a huge obstacle. Fortunately, the recent availability of funds for HIV prevention and treatment for Africa from the Bush AIDS relief plan will likely make a huge difference in the implementation of this nevirapine regimen."
Because of the drugs' short duration, some babies in both treatment groups subsequently became infected with HIV, most likely through breast feeding, but the nevirapine group still had about 41 percent fewer HIV infections even after a year and a half. In other attempts to reduce mother-to-baby transmission of HIV, the initial gap in infections has gotten smaller over time.
Worldwide, roughly 800,000 babies are infected with HIV each year by mother-to-child transmission of the virus during gestation or birth or by drinking breast milk, according to UNAIDS and the World Health Organization. More than 90 percent of these babies are in resource-poor countries where treatment of HIV infection is not available to mothers, alternatives to breast milk aren't widely available and strategies used elsewhere to prevent mom-to-baby transmission are too expensive.
"In our study, single doses of nevirapine were more effective than a short course of AZT in preventing HIV transmission during birth and in the first weeks after birth," says Jackson, who led the study with Francis Mmiro, F.R.C.O.G., of Makarere University in Kampala, Uganda.
Importantly, no serious adverse events were definitively linked to either drug in the trial, into which the last participants were enrolled in April 1999. Although concerns regarding nevirapine's safety have been raised over the last few years, this and other studies of the drug at this dosage prove it is safe, the researchers say.
"We actually saw more rashes and other adverse events in the AZT group than the nevirapine group, and even though there were a few serious adverse events in both groups, none could be conclusively tied to either study drug," says Jackson.
When nevirapine is used for a long time in high doses, and in combination with other antiretroviral drugs, serious rashes and liver problems are the most common and dangerous side effects. But Jackson emphasizes that the one-time doses used in the mother-to-baby prevention study are just a fraction of those used in treatment.
Nevirapine's manufacturer, Boehringer-Ingelheim, has offered the drug for free to less-developed countries for use in efforts to prevent mother-to-child transmission, but only through agreements with governments, not individual hospitals or clinics.
In the study, 308 mothers and their babies received AZT, and 311 pairs of mothers and infants received nevirapine. Women in the AZT group received 600 milligrams when labor began, and additional doses of 300 milligrams every three hours until delivery. Babies in this group received small, twice daily doses of AZT for a week. Women in the nevirapine group received a single 200 milligram dose of the drug at the beginning of labor, and babies received a small dose within three days of birth.
At 6 to 8 weeks of age, 59 babies in the AZT group were HIV positive, while only 36 babies in the nevirapine group were HIV infected. By 18 months of age, 75 babies in the AZT group and 47 in the nevirapine group were HIV positive. Because infant mortality is quite high in less-developed nations, the researchers also analyzed the data using death or HIV infection as the endpoint, and the gap between the nevirapine and AZT groups was still present (63 babies in the nevirapine group and 92 babies in the AZT group at 18 months had died or were HIV positive). Results will be reported again once all babies reach age 5.
The study was funded by the National Institute of Allergy and Infectious Diseases (NIAID) and funded by and conducted through the HIV Prevention Trials Network, which is principally funded by NIAID and is co-sponsored by the National Institute of Child Health and Human Development (NICHD), the National Institute on Drug Abuse, the National Institute of Mental Health and the National Institutes of Health's Office of AIDS Research. Nevirapine was provided by Boehringer-Ingelheim Pharmaceuticals.
Authors on the paper are Jackson, Laura Guay, Joseph Sherman, Constance Ducar and Corey Duefield of Johns Hopkins; Mmiro, Philippe Musoke, Paul Bakaki, Maxensia Owor, Danstan Bagenda and Clemensia Nakabiito of Makarere University, Kampala, Uganda; Thomas Fleming, Martina Deseyve, Lynda Emel and Anthony Mwatha of the Fred Hutchinson Cancer Research Center, Seattle; Melissa Allen, Family Health International, Durham, NC; Mark Mirochnick, Boston University; Mary Glenn Fowler and Paolo Miotti, NIAID; Lynne Mofenson, NICHD; Maria Gigliotti, Boehringer-Ingelheim Pharmaceuticals, Ridgefield, CT; and Dorothy Bray, Glaxo-Wellcome, London.
Jackson has received a one-time consulting fee from Glaxo-Wellcome, and Jackson and Guay have received honoraria from Boehringer-Ingelheim, the maker of nevirapine. For full disclosure on all authors, refer to the scientific paper.
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