July 2, 2004 -- The first clinical trial of a generic combination of drugs for AIDS has demonstrated that the generic combination works as well as band name drugs. The trial will be reported in the July 3 issue of the English medical journal The Lancet.
The Lancet report has important implications for American foreign health policy. "This issue is important because the United States has refused to let the $15 billion that President Bush has committed to fighting AIDS in the third world be used for generic drugs, arguing that there is not enough proof they are effective," noted The New York Times.
The generic combination in the trial consisted of nevirapine, stavudine and lamivudine made by Cipla Ltd. of Mumbai, India. The brand names for these drugs are Viramune, Zerit and Epivir, respectively.
A Most Unusual Clinical Trial
The makers of generics normally do not need to carry out trials of their products. They need only prove that their drugs are chemically identical to brand-name drugs. So this clinical trial of generic drugs is most unusual.
The clinical trial was done in Yaounde, the capital of Cameroon in West Africa. Nearly all the patients were in the far advanced stages of AIDS. By the end of the trial, the generic combination pill had driven down the HIV virus to very low levels in 80% of patients. And most of the patients had increases in CD-4 cells, the cells that HIV attacks.
The clinical trial was done by the Cameroon National AIDS Program, Medecins Sans Frontieres (Doctors Without Borders) in Switzerland, and the Institut de Recherche pour le Developpement at the University of Montpellier in France. The research was supported by a grant from the French National Agency for Research on AIDS (ANRS).
What is at stake here is, of course, money. It is prohibitively expensive to use brand-name drugs to treat a poor person with HIV in a developing country. The cost of the generic combination pill is $250 a year.
We have read the original report of this clinical trial which is online in The Lancet. The trial appears to have been very well done and carefully documented.
We agree with the researchers that their "findings lend support to use and funding of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine as first-line antiretroviral treatment in developing countries."
What the response of the Bush administration will be now, we do not know. We hope that it will be positive. The $15 billion that President Bush committed to fighting AIDS in the third world should immediately become available to, among other things, buy generic drugs.
The main continents with developing nations attacked by the AIDS epidemic are Africa and Asia. The prompt implementation of an intelligent policy on AIDS may help the image of the US in Africa and Asia and, we hope, all around the world.
Lancet Report Summary
Background: Generic fixed-dose combinations have been prequalified by WHO to treat HIV-infected patients in resource-limited countries. Despite their widespread use they are, however, not yet recommended by some of the major donor agencies owing to scarcity of clinical data on effectiveness, safety, and quality. We aimed to assess these issues for one of the most frequently prescribed treatments in Africa, a generic fixed-dose combination of nevirapine, stavudine, and lamivudine.
Methods: 60 patients were followed in an open-label, 24-week multicentre trial in Cameroon. All patients received one tablet of the fixed-dose combination drug twice daily. The primary outcome measure was the proportion of patients with viral load less than 400 copies per mL at the end of the study period, in an intention-to-treat analysis.
Findings: At baseline, 92% of patients (n=55) had AIDS; median CD4 count was 118 cells per µL (IQR 78-167) and median plasma HIV-1 RNA was 104 736 copies per mL (40 804-243 787). The proportion of patients with undetectable viral load (<400 copies per mL) after 24 weeks of treatment was 80% (95% CI 68-89). Median (IQR) change in viral load was -3·1 log10 copies per mL (-2·5 to -3·6) and in CD4 count 83 cells per µL (40-178). The probability of remaining alive or free of new AIDS-defining events was 0·85 (95% CI 0·73-0·92). Frequency of disease progression was 32·0 (95% CI 16·6-61·5), severe adverse effects 17·8 (7·4-42·7), and genotypic resistance mutations 7·1 (1·8-28·4) per 100 person-years. Mean reported adherence rate was 99%. Median drug concentrations in tablets were 96% of expected values for nevirapine, 89% for stavudine, and 99% for lamivudine.
Interpretation: Our findings lend support to use and funding of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine as first-line antiretroviral treatment in developing countries.
Source: Effectiveness and safety of a generic fixed-dose combination of nevirapine, stavudine, and lamivudine in HIV-1-infected adults in Cameroon: open-label multicentre trial. Christian Laurent and colleagues. The Lancet 2004; 364: 29-34.