HIV-Positive Pregnant Women Who Take One Dose of Nevirapine at Delivery Could Develop Drug-Resistant HIV, Study Says

HIV-positive pregnant women who take a single dose of the antiretroviral drug nevirapine at delivery to prevent vertical HIV transmission later could develop drug-resistant HIV, according to a study presented on Monday at the 11th Conference on Retroviruses and Opportunistic Infections, the San Francisco Chronicle reports (Russell, San Francisco Chronicle, 2/10). Health officials since 1999 have suggested that HIV-positive pregnant women receive a single dose of nevirapine during labor and the infant receive nevirapine once within the first three days after birth to reduce the risk of mother-to-child HIV transmission, the New York Times reports. The treatment has been shown to reduce the risk of vertical transmission from 25% or more to 12% (Altman, New York Times, 2/10). The study, led by Dr. Neil Martinson of the National Institute for Communicable Diseases in Johannesburg, South Africa, enrolled at two large hospitals 623 HIV-positive women who were 32 weeks to 38 weeks pregnant. Researchers' findings were based on baseline assessments and follow-up at six weeks postpartum. Researchers examined 456 women at a median time of seven weeks after delivery (Study abstract, 2/9). Researchers found that 8.6% of the infants born to the women were HIV-positive (San Francisco Chronicle, 2/10). According to the results, 39% of the HIV-positive women and 42% of the infants who became infected despite receiving the drug later developed nevirapine resistance, USA Today reports. In addition, researchers found that the drug-resistant HIV persisted in the women and their infants for a minimum of 36 weeks (Sternberg, USA Today, 2/10).

Thai Study
Another study presented at the conference examined the use of zidovudine with a single dose of nevirapine in HIV-positive pregnant women in their third trimester and in their infants during the first week after birth, the Times reports (New York Times, 2/10). Researchers in France, Thailand and Massachusetts enrolled 1,844 HIV-positive pregnant women between January 2001 and March 2003. Participants were divided into three groups. Women and infants in the first group received a single dose of nevirapine, women in the second group were given nevirapine and the infants were given a placebo and both the women and infants in the third group were given a placebo. All of the women received some HIV prophylaxis during the third trimester of pregnancy, and their infants received at least one week of zidovudine following birth and were fed with formula (Study abstract, 2/9). Researchers found that among the women who delivered before an interim analysis was conducted, the estimated HIV transmission rate was 1% in the first group compared with 6% in the third group, leading researchers to abandon the dual placebo protocol, Reuters Health reports (Reuters Health, 2/9). Overall, about 2% of the infants whose mothers received zidovudine and nevirapine became infected, according to Agence France-Presse (Barollier, Agence France-Presse, 2/10). Following delivery, about 25% of the women began taking a triple-drug combination containing nevirapine, which was offered at no cost by the Thai government. After six months on the regimen, researchers examined blood samples from the women, the Washington Post reports. Researchers found that 75% of the women who had not taken nevirapine at delivery had undetectable levels of HIV in their bloodstream, according to the Post. Among women who had taken nevirapine but did not demonstrate drug resistance, 53% had undetectable viral loads, compared with 34% of women who were given nevirapine and who developed drug resistance after delivery.

Reaction
The results of the studies show that even brief exposure to nevirapine gives HIV a chance to develop resistance to the drug, which could "jeopardize the success of antiretroviral combinations containing it," the Post reports. Two of the four drug regimens recommended by the World Health Organization under its plan to treat three million HIV-positive people with antiretroviral drugs by 2005 contain nevirapine, according to the Post. Although the new information regarding nevirapine is "unlikely to put the brakes on the campaign ... over the long run it will make that herculean effort even more difficult," the Post reports. Isabelle de Zoysa, director of HIV prevention for WHO, said, "What remains to be determined is the clinical implications of this resistance, whether in Thailand or Africa or anywhere else," adding, "We don't yet know how many would need to be switched to a second-line regimen. ... The picture is not complete yet" (Brown, Washington Post, 2/10). Dr. Scott Hammer, an AIDS researcher from Columbia University, said that the data should be viewed with caution, noting that vertical HIV transmission rates have been reduced to 1% or below in the United States and other developed countries. "The use of antimicrobial drugs is always associated with the rise of resistance," Hammer said, adding, "The challenge is to see it in context." Elizabeth Glaser Pediatric AIDS Foundation President and CEO Kate Carr said, "Clearly the best course would be to get mothers on combination therapy, but the reality is that with limited resources, we are still going to need to use single-dose nevirapine" (Chase, Wall Street Journal, 2/10). Carr added, "The sad reality is that today, less than 1% of all HIV-positive pregnant women are getting even nevirapine alone. In most resource-poor settings, what will pregnant women have access to?" Dr. Elaine Abrams, an expert on vertical HIV transmission from Columbia University, said, "Single-drug therapy should not be withheld if no other alternative exists" (San Francisco Chronicle, 2/10).