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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

Natural immune responses are able to control viral replication from peak viraemia to viral set point in acute HIV-1 infection. However, these natural immune responses have not been fully characterised. Immune correlates of protection from HIV acquisition and progression to AIDS are not known, neither are the phenotypes of cells needed to be induced by HIV vaccines to confer protection.

Defining the precise correlates of the cellular immune response to HIV-1 that are associated with control of HIV-1 replication in acute infection, has been the focus of intense study over the past two decades. The identification of such correlates has been pursued as part of a rational strategy to produce an HIV-1 vaccine capable of best mimicking the cellular immune response associated with control of HIV-1 viraemia. Once defined, such correlates will also help establish the necessary benchmarks for candidate vaccine down selection and efficacy testing.

In this study, Dr Obuku will attempt to delineate the different T cell phenotypes (including lymph node resident memory T cells) and their ability to inhibit viral replication. He will characterise the CD8 T cell phenotypes, before peak viraemia, at peak viraemia, at set point and post set point from blood and lymph nodes. He will also investigate the cell death pathways associated with the death of CD8 T cells from peak viraemia to set point. Moreover, he will compare the ability of the different CD8 T cell phenotypes to inhibit HIV-1 replication in a viral inhibition assay and identify the most potent phenotypes of CD8 T cells at controlling HIV-1 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 results of this study will contribute to the body of research that aims to determine how HIV vaccines can induce the immune system to confer protection.

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