Six-Week Course of Antiretroviral Nevirapine Did Not Clearly Reduce Risk of HIV Among Breastfed Infants, Study Finds

A six-week extended course of the antiretroviral drug nevirapine did not clearly show a reduced risk of mother-to-child HIV transmission among breastfed infants, according to a study published Saturday in the journal Lancet, the New York Times reports. According to the Times, breastfeeding "presents a life-and-death dilemma" for HIV-positive mothers in developing countries. Although using formula can reduce the risk of MTCT, when formula is mixed with dirty water, it can increase the risk of death among infants from causes such as diarrhea and malnutrition. In most developing nations, women will continue to breastfeed because it is traditional, formula is expensive and because using formula "announces" that a woman is HIV-positive, according to the Times. At least 150,000 infants contract HIV through breastfeeding annually, experts estimate.

In an effort to prevent MTCT, researchers have "stumbled into their own terrible dilemma," the Times reports. A single dose of nevirapine can prevent MTCT, but a single dose is not always effective. In addition, nevirapine can have side effects, and some infants develop liver failure, rashes or low white blood cell counts. Resistance to nevirapine also develops quickly, meaning that an infant who receives nevirapine and still contracts HIV will be unable to combination therapies that contain it or any related drug (McNeil, New York Times, 7/29).

For the study, researchers administered nevirapine to infants in Ethiopia, India and Uganda whose mothers were HIV-positive (Britt, Bloomberg, 7/25). The infants were randomly assigned to receive a single dose of the drug, while the other half received a six-week course (Bollinger et al., Lancet, 7/26). The study found that infants who took daily doses of nevirapine for six weeks reduced their risk of MTCT by 15% (Bloomberg, 7/25). "Although a six-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at six weeks of age, the lack of a significant reduction in the primary endpoint -- risk of HIV transmission at six months -- suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breastmilk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high," the researchers wrote (Lancet, 7/26).

However, three members of the research team led by Mrudula Phadke of the Maharshtra University of Health Sciences in Nashik, India, in a letter to the journal wrote that it is "wrong that a drug that has not shown significant benefit and which has serious toxic side effects in 38.4% of babies should be tried for longer." The study's design of six months was based on the 10 to 14 days that it takes nevirapine to build up in infants' blood, the three researchers wrote in the letter, adding that the finding that incidence was lower after six weeks "does not reflect the effect of six weeks of treatment at all." Instead of using nevirapine, HIV/AIDS experts should focus on methods to make infant formula more available and acceptable to HIV-positive mothers in developing countries, the researchers added.

The disagreement among the study's authors is unusual, Lancet editors Pia Pini and Sabine Kleinert wrote in an accompanying commentary. They added that NIH, which funded the study, said there was no "breach of research integrity." They added, "In our opinion, publication of these important data, with complete disclosure, is the best course of action." Jeffrey Stringer and Benjamin Chi from the University of Alabama-Birmingham wrote in an accompanying commentary that "[e]xtended infant prophylaxis with nevirapine is simple enough to be implemented almost anywhere. It represents a long-awaited, if partial, solution to a mother's impossible choice. We should not delay" (Bloomberg, 7/25).

The study is available online. The letter also is available online.