Prenatal HIV prevention combo reduces resistance

NEW YORK (Reuters Health) - The addition of a single dose of a two-drug combination can prevent the development of resistance in pregnant HIV-infected women who receive a short-course regimen of nevirapine (Viramune) to prevent transmission of the virus to their infant.

HIV-positive women who have not been treated with anti-HIV drugs, or who had not been aware they were infected, can be given a short course of nevirapine when they go into labor that can prevent the transmission of HIV to the newborn.

This approach was initially developed for use in areas with very limited resources and where anti-HIV drugs were not available. Although exposure to nevirapine in the short-course regimen is brief, there have been reports that drug resistance can develop in these women.

Treating HIV infection with a single drug is known to induce resistance to that drug as well as to the entire class of drugs, limiting a patient's further treatment options. This is why drug combinations are always used to treat HIV infection.

Previous reports have suggested that up to 69 percent of pregnant women treated with nevirapine will develop resistance to the drug and to other nonnucleoside reverse transcriptase inhibitors (NNRTIs). While there is evidence that the gene mutations causing resistance are only temporary, their long-term impact on future anti-HIV therapy is unclear. Therefore, the goal has been to avoid their development in the first place.

Now, investigators report that adding a single dose of tenofovir (Viread) and emtricitabine (Emtriva) to nevirapine can prevent the development of resistance to nevirapine and NNRTIs. The combination of tenofovir and emtricitabine is also available in one pill (Truvada).

Still, according to the authors, the regimen may require certain refinements. "Despite its effectiveness, this intervention might need modification to provide the optimum protective effect," lead author Dr. Benjamin H. Chi and colleagues state.

"Nevertheless, it is an important adjunct to regimens that incorporate (the NNRTI) nevirapine and should be considered in settings where drug combinations to be taken over several days might be impractical for patients or for local health infrastructure," they add.

The results, which appear in The Lancet, are based on a study of 400 HIV-infected pregnant women in Zambia who were randomly assigned to receive tenofovir/emtricitabine or no study drug in combination with nevirapine.

Eighty-one percent of the women also received a short course of zidovudine (Retrovir), also known as AZT. Standard blood tests showed that all of the women had relatively intact immune systems when the study began.

Compared with the placebo group, those in the tenofovir/emtricitabine group were 53 percent less likely to have a gene mutation that confers resistant to NNRTIs after 6 weeks.

Adding tenofovir/emtricitabine to nevirapine and zidovudine therapy is "a new, effective, and feasible approach to reducing maternal nevirapine resistance, and one that should be seriously considered for implementation," Dr. Shahin Lockman, from Brigham and Women's Hospital in Boston, and Dr. James Alasdair McIntyre, from the University of Witwatersrand in Johannesburg, South Africa, comment in a related editorial.

SOURCE: Lancet, November 7th online issue 2007.