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test the safety and efficacy of this new formulation in young children

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Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

Human immunodeficiency virus type 2 (HIV-2) is a retrovirus responsible for an AIDS epidemic localised in West Africa, were the circulation of both HIV-1 and HIV-2 leads to co-infections with both viruses. The HIV-2 infection is characterised by a longer asymptomatic phase and a slower disease progression than HIV-1 infection, as well as the intrinsic resistance of HIV-2 to non-nucleoside reverse transcriptase inhibitors. It is mandatory to differentiate HIV-1 from HIV-2 infection before initiating antiretroviral therapy (ART), but the diagnosis is still challenging, especially for the HIV-1 and HIV-2 dually infected individuals

The challenge is to explore new diagnostic algorithms based on routinely used HIV rapid tests, to ensure the peripheral diagnosis of patients with dual infection in West Africa. The related challenge is to describe the epidemiology of HIV-2 and dual infection in West Africa.

Guidelines for antiretroviral therapy neglect HIV-2 infected patients due to conflicting reports on the epidemic trend of HIV-2 infection and a lack of recent data. Furthermore, the important mortality reported among HIV-2 infected individuals may be the consequence of immune activation and persistence of soluble biomarkers as demonstrated in HIV-1 infection.

Dr Tchounga’s three-year research project relies on the West African HIV-2 cohort, and the related biobank to evaluate a new diagnostic algorithm for HIV-1 and HIV-2 dual infection. The study will also produce more accurate and updated epidemiological data on HIV-2 infection. Finally, it is exploring disease progression and the prognostic role of immunologic and inflammatory markers in HIV-2 infection.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The project aims to provide the much needed accurate epidemiologic data, improved diagnosis of HIV-2 patients and a better understanding of the dynamics and correlates of disease progression. These results may help inform specific guidelines for HIV-2 infection. Capacity development is integrated into the project through training of graduate students in epidemiology, immunology and biostatistics.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact