Combination Therapy Might Be Better Choice Than Nevirapine Alone To Prevent Vertical HIV Transmission, Researchers Say
Antiretroviral drug combination therapy might be more effective in preventing mother-to-child HIV transmission and less likely to foster drug resistance among pregnant women than single-dose nevirapine, according to data presented this week at the 12th Conference on Retroviruses and Opportunistic Infections in Boston, the Washington Post reports. Single-dose nevirapine has been administered to about 500,000 HIV-positive pregnant women in developing countries over the past five years, and some studies have suggested that this method has cut the rate of vertical HIV transmission by 50%. However, some studies also have shown that single-dose nevirapine might foster drug resistance in many women who take the drug, effectively "clos[ing] off" future treatment options, according to the Post.
However, studies presented at the conference show that the provision of one or two other antiretrovirals in addition to nevirapine around the time of delivery has "clear benefits," including reducing vertical transmission rates to as low as 2% and decreasing the risk of drug resistance among pregnant women, the Post reports. One study involved nearly 1,200 pregnant women in Botswana, some of whom received zidovudine beginning at 34 weeks gestation and a single dose of nevirapine during labor and some of whom received only zidovudine. In both groups, newborns received a single dose of nevirapine after birth and one month of zidovudine therapy. The study found that both groups had vertical transmission rates around 6%, according to the Post (Brown, Washington Post, 2/25). In another study conducted in Cote d'Ivoire, 329 pregnant women began taking Combivir -- which contains zidovudine and lamivudine -- at eight months gestation and a single dose of nevirapine at the beginning of labor. The women also took Combivir for three days following delivery, and their newborns were given zidovudine for one week and a single dose of nevirapine two days after delivery. The researchers found that 4.7% of infants tested HIV-positive six weeks after delivery, and 1.1% of women had developed resistance to nevirapine (Smith, Boston Globe, 2/25). Previous studies have shown that about 20% of women who take single-dose nevirapine develop drug resistance and about 12% of infants born to women who took single-dose nevirapine contract HIV, according to the Post.
According to other data presented at the conference, the 1.1% drug-resistance rate observed in the Cote d'Ivoire study might be an underestimate because extremely sensitive tests demonstrate that as many as 40% of blood samples that test negative for nevirapine resistance actually harbor resistant strains in "very small quantities," the Post reports. "We need to see what happens when those women start therapy. We don't know yet whether it will make a difference," Mary Fowler, a CDC pediatrician who heads the agency's efforts to reduce vertical HIV transmission, said. Charles Gilks, head of the World Health's Organization's 3 by 5 Initiative -- which aims to treat three million HIV-positive people with antiretrovirals by the end of this year -- said that the agency plans to convene a panel within the next few months to review its recommendations on nevirapine use. James McIntyre, a South African physician who specializes in pediatric HIV/AIDS, said, "I think we're leaving at the end of this week with a different world view" (Washington Post, 2/25).
Other AIDS advocates and researchers said that until combination therapy is more widely available, single-dose nevirapine should continue to be administered "even in the face of concerns about resistance," according to the Globe (Boston Globe, 2/25). The Elizabeth Glaser Pediatric AIDS Foundation in a release said that it is "essential to preserve single-dose nevirapine as an option" because even "simple interventions like nevirapine are still available to less than 10% of the women who need them worldwide. Therefore, we must continue to aggressively expand access to [mother-to-child transmission prevention] services and improve our ability to offer the most effective drug regimens in all instances" (EGPAF release, 2/23). The cost of combination therapy also might be "prohibitive" in the developing world, according to the AP/Las Vegas Sun. Some combinations could cost more than twice as much as the $8 it costs to administer single-dose nevirapine to a pregnant woman and her infant, the AP/Sun reports (Donn, AP/Las Vegas Sun, 2/24). EGPAF Vice President Mark Isaac said the group, which works at more than 600 sites in 19 countries, will move toward using treatment strategies other than single-dose nevirapine when possible, according to the Post (Washington Post, 2/25) .