Phase III study influences WHO to change guidelines for HIV-infected women receiving nevirapine

Oct 18 2010

Findings from a study, which appear in the Oct. 14, 2010 New England Journal of Medicine, helped influence the World Health Organization (WHO) to change its guidelines this year for the treatment of HIV-infected women who receive a single dose of the antiretroviral drug nevirapine to prevent HIV transmission to their babies. The study demonstrated that the single dose of nevirapine used to prevent mother-to-child transmission of HIV can hamper the drug's effectiveness if it is also used later as part of a regimen to treat these same individuals.

The Phase III study, called Optimal Combination Therapy after Nevirapine Exposure (OCTANE), enrolled 745 women at 10 sites in seven African countries to address the critical question around nevirapine resistance. The drug nevirapine is inexpensive and accessible, and is widely used in resource-constrained settings for both treating HIV and preventing mother-to-child transmission (PMTCT).

The Adult AIDS Clinical Trials Group conducted the study with funding from the National Institute of Allergy and Infectious Diseases (NIAID), part of the U.S. National Institutes of Health. The U.S. Military HIV Research Program's (MHRP) network site in Kericho, Kenya, the Kenya Medical Research Institute/Walter Reed Project, and another partner site in Eldoret, Kenya, participated in the study and enrolled 74 participants.

"This is very exciting news indeed!" said Dr. Fred Sawe, MHRP partner and the local principal investigator for the OCTANE study in Kericho. "We now have a definite answer to a problem that has continued to haunt us for the last 10 years. Given the infrastructure we have so far built in PMTCT programs, we can now minimize use of single dose only nevirapine-based interventions, increase access to more efficacious regimens, and provide better care to women who have been exposed to single-dose nevirapine without slowing down the progress of eliminating pediatric AIDS: a win-win situation of great public health importance."

An interim review of the study in 2008 found that exposing HIV-infected women to a single dose of nevirapine for PMTCT may lead these women to develop nevirapine-resistant HIV. The development of drug resistance compromises the effectiveness of HIV treatment regimens that include nevirapine. Based on this information, the study leadership advised women who were previously exposed to nevirapine and were taking nevirapine as part of the study protocol to consult with their clinicians about how to proceed with HIV treatment.

One of the additional findings in the study was that the negative effect of previous exposure to nevirapine appears to decrease with time. Researchers also found that the negative effect appears to decrease when more time elapses between taking single-dose nevirapine and starting treatment. The study also found that for those women without prior exposure to nevirapine, the drug has similar efficacy to another regimen, which included ritonavir-boosted lopinavir.

The 2010 WHO guidelines now advise that HIV-infected women who take single-dose nevirapine for PMTCT should not be treated for their own infection with a drug regimen that includes nevirapine as well as other drugs in the same class (known as non-nucleoside reverse transcriptase inhibitors, or NNRTIs), if treatment begins fewer than 12 months later and if the women were not given other antiretroviral drugs to prevent the development of nevirapine-resistant HIV.

Source: Henry M. Jackson Foundation for the Advancement of Military Medicine