Generic tritherapy can be used as a basic treatment for AIDS

Sep 5 2004

Access to antiretroviral therapies for people living with HIV in the developing countries is a major world health priority.

One of the strategies adopted consists in utilizing combinations of fixed doses of generic antiretrovirals, involving three medicinal drugs of two different classes in the same tablet. These combinations, however, have never been fully evaluated and therefore raise questions as to their efficacy and safety.

A clinical trial, conducted in Cameroon by IRD researchers working with other organizations and supported by the ANRS, has demonstrated that one of the most common combinations currently deployed in Africa, using nevirapine, stavudine and lamivudine, satisfies these criteria. The full results, published and discussed in the journal The Lancet, confirmed that this generic tritherapy can be used as a basic treatment in the developing countries.

WHO's objective is to enable 3 million people living with HIV to have access to antiretroviral treatments by 2005. The development of simple and inexpensive generic fixed-dose combined therapies appears the most suitable solution for making possible this access to treatments in developing countries with meagre resources.

The tritherapies that associate two different classes of antiretrovirals (two nucleoside reverse transcriptase inhibitors and one non-nucleosidic inhibitor of this same viral enzyme), used as a basic treatment, are effective and well tolerated. Their combined form in a single tablet, developed by a firm producing generic drugs, encourages better treatment compliance by the patient and simplifies management of orders and storage of the medicines. Their cost is much lower than that of tritherapies of patented medicines (2). Consequently, these combined generic forms provide the possibility of treating more subjects infected with HIV. However, although prequalified by WHO and available in many developing countries, at present some international aid agencies involved in programmes of access to antiretrovirals do not recognize them. The main reason cited is the absence of full clinical studies that could allow assessment of their effectiveness, safety and quality.

Researchers from the IRD and their partners have just shown, by means of a clinical trial performed in Cameroon, that the generic fixed-dose antiretroviral tritherapy currently most commonly used in Africa satisfied these criteria. This treatment uses a combination of a dose of nevirapine, one of stavudine and one of lamivudine in a single tablet.

The trial was conducted by means of a pilot project of access to the antiretroviral medicines initiated in Yaoundé, the capital of Cameroon. For six months, 60 adults infected by HIV-1 were treated with one tablet twice a day, in two of the city's hospitals. Clinical and biological monitoring of these infected subjects kept a close check on their health status with time and evaluated the effectiveness, the tolerance and treatment compliance. The appearance of resistance and the quality of the different batches of medicines administered as part of the trial were also investigated.

At the end of six months of treatment, the viral load was undetectable (below 400 copies/ml) in 80% of patients. The T CD4 lymphocyte count was increased by 83 cells/µl, indicating a satisfactory level of immunity restoration. The treatment applied thus turned out to be as effective as conventional tritherapies. According to patients' accounts, in 99% of cases the medicines were taken in compliance with prescriptions. This very good compliance with treatment was confirmed by regular measurement of blood concentrations of each of the three antiretrovirals. Out of 60 people in the study, only one case of intolerance was found, necessitating a modification to the treatment. The researchers moreover observed two cases of resistance, one in a person who had not properly followed his prescribed treatment, the other in a woman who, before the start of trial, had received nevirapine in prevention treatment against mother-child HIV transmission.

In parallel, analysis of several tablets from each of seven boxes of generic medicines distributed to patients in the trial verified that these tablets effectively contained the active agents for which they were put on the market, in the expected doses (3).

These results showed that the generic fixed-dose tritherapy studied is at once effective, well tolerated and of high quality. They provide arguments in favour of its use as basic treatment in the developing countries.

The study is currently being continued with the aim of finding long-term confirmation of the results obtained. These are the subject of a publication and discussion in the journal The Lancet of 3 July. They will be presented at the international conference on Aids, to take place in Bangkok, in mid July.