Combination therapy with three generic antiretroviral drugs in a single tablet has been validated for the first time in an open clinical study in a developing country. Follow-up of 60 patients treated in Yaoundé, Cameroon, has demonstrated the excellent efficacy and safety of a generic fixed-dose combination.
The results of this clinical trial (ANRS 1274) have been published in The Lancet by a team of researchers from the Institut de recherche pour le développement (IRD), Cameroon and Médecins sans Frontières (MSF) Switzerland.
Generic fixed-dose combinations (FDCs) of antiretrovirals are a key factor in access to treatment of HIV/AIDS infection in the developing world. FDCs combine three antiretroviral drugs in a single tablet and have the twofold advantage of being simple to use and substantially cheaper than brand name drugs.
Lack of scientific evidence for the efficacy of FDCs has until now caused some international AIDS donors to refuse to fund the use of these treatments, even though they have recently been prequalified by the WHO.
ANRS 1274 is the first trial to provide scientific evidence for the efficacy and safety of an FDC in a clinical study. The results were published in the 3 July 2004 issue of The Lancet.
ANRS trial 1274 was conducted in two hospital centers in Yaoundé (Central Hospital and Military Hospital) within the framework of the Cameroon AIDS Control Program by a team of researchers from the IRD, Cameroon and MSF/Switzerland. Of the 60 HIV-infected patients included, 92% had full-blown AIDS. The patients were treated with Triomune®, an FDC combining generic versions of three antiretroviral drugs from two different classes: lamivudine, stavudine and nevirapine. The treatment regimen was one tablet morning and evening.
Triomune® is produced by the Indian pharmaceutical company Cipla. This generic combination is now one of the most used in first-line treatment in the developing world.
"This trial demonstrates in a perfectly rigorous manner that FDCs can be prescribed in first-line treatment in the developing countries", explained Eric Delaporte of the IRD/University of Montpellier, who coordinated the study with Sinata Koulla-Shiro of the Central Hospital and Eitel Mpoudi-Ngole of the Military Hospital of Yaoundé. The results recorded after six months of follow-up showed that viral load was undetectable in 80% of patients.
Immune reconstitution was significant, with a median increase of 83 CD4 lymphocytes/mm3 after six months. Treatment safety was excellent, with a single discontinuation of therapy due to adverse drug reactions.
A pharmacological study showed that plasma antiretroviral concentrations were fully satisfactory and equivalent to those observed in patients treated with brand name drugs.
"This generic fixed-dose combination gives results comparable to those seen in the developed world using triple-drug therapy comprising brand name drugs", noted Eric Delaporte. "Thanks to these findings it is now no longer possible to raise scientific uncertainty as an objection to the widespread utilization of FDCs in the developing countries ". Nevertheless, "the study must be pursued to confirm these excellent results over the longer term" commented the Minister of Public Health in Cameroon, Mr. Urbain Olanguena Awono.
In Cameroon, where antiretroviral therapy is state-subsidized, the monthly cost of Triomune® treatment is 20 US dollars, compared with 35 dollars for equivalent triple-drug therapy with brand name drugs. Cost differences could vary by as much as 100% in other countries. The demonstrated efficacy of generic FDCs means that from now on more HIV-infected people should be able to access to treatment.