Olivier DARGOUGE

Generic combination HIV/AIDS drugs formulated into a single pill are "at least as [effective] as highly active antiretroviral therapy in industrialised countries", according to research published in this week's issue of The Lancet.

Christian Laurent, of the French Institut de Recherche pour le Développement (IRD) and his colleagues took advantage of a pilot project on access to antiretroviral drugs in Yaoundé, the capital of Cameroon, to test the efficacy, safety and quality of one of the most commonly used fixed-dose combination (FDC) therapies used in Africa.

The drug is a single pill combining fixed dosages of three active ingredients (nevirapin, stavudin and lamivudine) and is made by the Indian pharmaceutical company Cipla. According to the World Health Organisation (WHO), it is not yet on their list of prequalified products — a list of medicines that meet WHO standards for the treatment of HIV/AIDS, malaria and tuberculosis — but a similar product is very close to being added.

Olivier Gross, of the prequalification office at the WHO told SciDev.Net that he was not surprised at the result, but added, "It is interesting to have a study proving the efficacy 'in the field' of the fixed dose combination."

Drugs on the prequalified list are assessed on the basis of a dossier, then tested in WHO-contracted labs. In some cases, and this one in particular, drugs can be put on the list based on a 'bioequivalency' application — showing equivalence to an approved product.

Laurent and his colleagues monitored 60 HIV positive adults for six months. The patients, who had never taken antiretrovirals before, were given one pill twice a day.

At the end of the six months, the researchers found that the amount of virus present in the patient blood plasma samples was undetectable in 80 per cent of patients. In addition, the number of CD4 cells — the cells HIV targets — had increased to a level indicative of a satisfactory restoration of the patients' immune systems.

This, they say, demonstrates that the treatment is as efficient as therapies used in developed countries.

Nathan Ford, of Médecins Sans Frontières (MSF) UK, told SciDev.Net: "This study confirms the safety and efficacy of the simplest and most affordable treatment regimen. This fixed-dose therapy is used widely by MSF. As of May 2004, 76 per cent of new patients within MSF projects started treatment on the one-pill-twice-a-day regimen. The FDCs reduce the pill burden, encouraging adherence and facilitating drug supply."

Part of the difficulty in treating patients in developing countries is making sure they adhere to their drug regimens. This task is made easier by single-pill treatments.

"There is an urgent need for new and alternative first-line FDCs to be developed," adds Ford. "So far, however, originator companies have been unwilling to co-operate to produce fixed-dose combinations due to competing patents on individual products, and these are only available from generic producers."

The study also looked at the quality of the generic drugs. The researchers analysed the composition of several pills from each batch distributed to patients and found that they did indeed contain the correct active ingredients in the advertised dosages.

These results come just ten days prior to the launch of the 15th International AIDS Conference in Bangkok on 11 July. It is expected that the matter of generic HIV/AIDS therapies will be a focus of the debates there, particularly in the light of the criticism that the US government has received for its lack of support for generic HIV/AIDS drugs.

"In the past the US government has opposed the use of this combination (FDCs)," says Ford. "However, given the overwhelming evidence and experience of the safety and effectiveness of this regimen, all donors should vigorously encourage and support their use."

Laurent's research was the result of a collaborative project. Primary collaborators were the IRD, the National AIDS Program (Yaoundé), the central and military hospitals in Yaoundé, and MSF (though Nathan Ford, quoted above, was not an investigator on the project).

Reference: The Lancet 246, 29 (2004)

Link to full research paper by Laurent et al in The Lancet*

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