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Use of AIDS Medicine Might Be Altered to Avert Drug Resistance

Unavoidably, however, the mother's nevirapine dose also works as a short course of single-drug HIV treatment. AIDS researchers learned more than a decade ago that such antiretroviral "monotherapy" does a person little good in the long run. Its primary effect is to simply make a patient's virus resistant to the drug. Only combinations of antiretrovirals -- at least three, sometimes four -- can suppress virus growth for long periods and possibly prevent the emergence of mutant, drug-resistant strains.

The research presented here this week will not lead to the abandonment of nevirapine. Instead, nevirapine may be used differently or in combination with other drugs.

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A study of 1,200 pregnant, HIV-infected women in Botswana found that if mothers receive AZT from the 34th week of gestation, and their babies get single doses of nevirapine and a month of AZT, then eliminating the mother's nevirapine would not make a difference. By a month after delivery, about 6 percent of the babies were infected, whether or not their mothers had taken nevirapine.

A study in the Ivory Coast showed an even lower transmission rate when women took a single dose of nevirapine along with AZT and lamivudine (which is sold under the trade name Combivir, but is also available as a low-cost generic). Babies got nevirapine and a week of AZT. By six weeks after delivery, only 4.7 percent of the infants were infected.

That strategy also called for women to take Combivir briefly after delivery so that they would effectively continue to be on "triple-therapy" while the nevirapine dose wore off. Nevirapine-resistance was found in only 1 percent of blood samples. That compares with about 20 percent of samples when nevirapine is given alone.

Other data presented here suggest that the rate of resistance may be an underestimate. Very sensitive tests show that perhaps 40 percent of blood samples that show no nevirapine-resistant virus actually harbor resistant strains in very small quantities.

"We need to see what happens when those women start therapy. We don't know yet whether it will make a difference," said Mary Fowler, a pediatrician at the Centers for Disease Control and Prevention who heads that agency's efforts to reduce mother-to-child transmission.

Charles Gilks, who heads the World Health Organization's project to help countries in the developing world put 3 million people on antiretroviral treatment by the end of 2005, said the agency will convene a panel of experts in the next few months to review its recommendations on nevirapine use.

Mark Isaac, a spokesman for the Elizabeth Glaser Pediatric AIDS Foundation, said the organization will now push for strategies that go beyond single-dose nevirapine at more than 600 sites in 19 countries where it works.

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