AIDS drug combo recommended by who comes under fire

A new analysis of research evidence suggests that one of the AIDS drug regimens increasingly used in developing countries and recommended by the World Health Organization (WHO), may have an unacceptably high risk of failure and rate of drug resistance in patients. The study, led by the Stanford University School of Medicine, appears in the March 15 print issue of the journal Clinical Infectious Diseases. In an editorial, eminent researchers call for a clinical trial of the tenofovir/lamivudine/nevirapine combination to decide whether it should stay on the WHO recommended list. In 2010, the WHO revised its treatment guidelines for HIV, replacing some older, more toxic treatments with four new regimens. All four regimens include the antiretroviral drug tenofovir, in combination with either lamivudine or emtricitabine, plus one or other of another pair, nevirapine or efavirenz. The WHO guidelines are important because most developing countries rely on them when devising their own treatment guidelines. Such regions contain the majority of the 5 million people worldwide who are currently receiving life-saving HIV treatment based on antiretroviral drug combinations. Principal investigator Dr Robert Shafer, a professor in the Department of Medicine, in the Division of Infectious Diseases, at Stanford University in California, and colleagues, sifted through 1,800 journal papers and conference abstracts and found 33 studies that had studied the efficacy of the four new drug combinations newly recommended by WHO. The least expensive of the four drug combinations recommended by the WHO is one that combines tenofovir with lamivudine and nevirapine. Shafer and colleagues could find only three studies covering this combination. Two of the studies were of trials that had to stop early because of high failure rates in the first three to four months. And the third was a retrospective study of antiretroviral therapies received by 9,000 patients in Nigeria, that showed the tenofovir/lamivudine/nevirapine combination had the highest failure rate. Shafer told the press that they followed "multiple lines of evidence", all of which "strongly suggested" this particular therapy poses a risk to successful treatment: "It's not just that it appeared inferior [compared to other alternatives] but among patients with treatment failure, drug resistance developed quickly," he added. The WHO-recommended tenofovir/lamivudine/nevirapine combination is increasingly being used in sub-Saharan Africa, said Shafer, where monitoring is too sparse to spot treatment failures. In such regions, virus load testing is not done as frequently, and resistance testing is often not done at all, said Shafer, noting it "could take several years to pick up problems". Shafer goes on to explain that unless a prospective study (one that follows people from the beginning) is set up, it will take a lot of retrospective data to confirm the concerns that he and colleagues have raised: that the tenofovir/lamivudine/nevirapine combination may have a failure rate that is unacceptable, compared to other treatments recommended by WHO. Researchers from Harvard Medical School, the University of Zimbabwe and the University of Witwatersrand in South Africa write in an accompanying editorial that they share these concerns. They urge international organizations, and drug manufacturers, to carry out a randomized clinical trial of the tenofovir/lamivudine/nevirapine combination's safety and effectiveness as a treatment for HIV, to decide whether it should stay on the WHO-recommended list.