Generic Fixed-Dose Combination Antiretroviral Drug Triomune as Effective as Brand-Name Treatment, Study Says
The generic fixed-dose combination antiretroviral drug Triomune is just as effective as brand-name antiretroviral drugs, according to the first clinical study of the drug in a developing country, Reuters reports (Hirschler, Reuters, 7/2). Researchers from the Universite Montpellier Institut de Recherche pour le Developement, the Agence National de Recherches sur la Sida and Medicines Sans Frontieres tracked 60 HIV-positive people in Cameroon for 24 weeks. The study is published in the July 3 issue of the Lancet. All participants received one Triomune tablet twice a day (Laurent et al., Lancet, 7/3). Triomune combines generic versions of stavudine, lamivudine and nevirapine into one pill that is taken twice a day and costs as little as $140 per person per year. A regimen of the same three drugs purchased separately from patent holders GlaxoSmithKline, Bristol-Myers Squibb and Boehringer-Ingelheim requires six pills a day and costs about $562 per patient per year (Kaiser Daily HIV/AIDS Report, 4/9). Almost all study participants were in advanced stages of AIDS, according to the New York Times (McNeil, New York Times, 7/2). At the start of the study, participants' median CD4+ cell count was 118 cells per microliter and participants had a median viral load of 104,736 copies per milliliter (Lancet, 7/3). Researchers found that after 24 weeks of treatment, 80% of participants had undetectable viral load levels -- less than 400 copies per milliliter, Reuters reports (Reuters, 7/2). Most participants also saw increases in their CD4+ cell counts, according to the Times (New York Times, 7/2). Study coordinator Eric Delaporte said that Triomune "gives results comparable to those seen in the developed world using triple-drug therapy comprising brand-name drugs."
Some international HIV/AIDS donors -- including the United States -- previously had refused to fund the use of generic FDCs because of a lack of scientific evidence supporting their efficacy, according to Reuters (Reuters, 7/2). The World Health Organization has established a prequalification review system with standards for safety and efficacy and has approved certain generic drugs -- including Triomune -- for use in developing countries. The United States recently announced plans for a new FDA fast-track review program to speed the delivery of low-cost antiretroviral drugs -- including generic and brand-name FDCs -- to countries covered under the President's Emergency Plan for AIDS Relief. U.S. officials wanted to ensure that the drugs would not contribute to the development of drug-resistant HIV strains through widespread or improper distribution and use (Kaiser Daily HIV/AIDS Report, 6/15). Dr. Mark Dybul, medical adviser to Ambassador Randall Tobias, head of the State Department Office of the Global AIDS Coordinator, said that although no generic drug companies so far have applied to the fast-track program, several "are expected to soon," according to the Times (New York Times, 7/2). Delaporte said that with the study results, it is "no longer possible to raise scientific uncertainty as an objection to the widespread utilization of FDCs in developing countries" (Reuters, 7/2).
Global Fund to Fight AIDS, Tuberculosis and Malaria Executive Director Richard Feachem said that the findings are "extremely good news," adding that the results "giv[e] strong scientific support for the procurement policies the Global Fund has been pursuing for 18 months" (New York Times, 7/2). Rachel Cohen of MSF's Access to Essential Medicines Campaign in the United States said, "I'm not naive. I know this won't change the purchasing policy" of the United States, but the study "makes it impossible to argue that such drugs aren't safe and effective." She added that the "bottom line is that a controlled study wasn't necessary" because the treatment was "already proven efficacious and safe" under the WHO prequalification program, but "given the political and ideological arguments being waged, investigators thought it necessary to carry out the study" (Chase, Wall Street Journal, 7/2). N. Kumarasamy of the YRG Centre for AIDS Research and Education in Chennai, India, said in an accompanying Lancet editorial that the study shows generic FDCs have a "major role to play" in WHO's 3 by 5 Initiative, which aims to treat three million people in developing countries with antiretroviral drugs by 2005, according to Reuters (Reuters, 7/2). However, Kumarasamy said that adherence to the drug treatment regimens, the high cost of "second-line combinations" with protease inhibitors, immunological and virological monitoring of patients taking antiretrovirals and the high incidence of opportunistic infections among patients taking antiretrovirals also show that doctors should be "trained properly before we scale up antiretroviral programs" in developing countries. He concluded, "We need to emphasize that physicians should adhere strictly to standard treatment guidelines to avoid antiretroviral failure and resistance which will be a future public health challenge in the presence of increasing use of generic antiretroviral drugs" (Kumarasamy, Lancet, 7/3).
The July 3 issue of the Lancet is a special feature focusing on HIV/AIDS in advance of the XV International AIDS Conference that will be held in Bangkok, Thailand, July 11-16. The issue includes commentary on the epidemic and articles on treatment, research, and the connection between health and human rights. The complete issue can be viewed online (Lancet, 6/3).