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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

Fortunately, large numbers of HIV-infected children now reach adolescence and then transition to adult HIV services because of the widespread use of ART in sub-Saharan Africa. Unfortunately, longstanding treatment of HIV infection is associated with damage to the heart and vasculature. Currently, there is a high burden of cardiac abnormalities in children and adolescents with perinatal HIV infection in sub-Saharan Africa. Cardiovascular disease risk is also related to alterations in vascular structure and function.

These problems, however, have not been systematically investigated in children and adolescents with a perinatal HIV infection. Moreover, most adolescents in sub-Saharan Africa have had a delayed diagnosis or initiation of ART. The impact of delayed ART on the vascular system is not known.

In this project, Dr Edith Majonga hypothesises that adolescents who have had an early start of ART will have better vascular characteristics compared to those who start ART much later. Therefore, those with a delayed start of ART start will have a higher risk of developing atherosclerosis. The study will cross-sectionally assess vascular characteristics, i.e. carotid intima-media thickness, flow-mediated dilation, pulse wave velocity and endothelial peripheral arterial tonometry, lipid profiles, insulin resistance and systemic inflammatory biomarkers. These characteristics will be compared to those of HIV-uninfected controls.

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.

A better understanding of cardiovascular disease epidemiology and risk factors in adolescents with perinatal HIV will leverage the extensive investments in the existing HIV care system by reducing cardiovascular disease morbidity and mortality. At an institutional level, the fellowship would contribute to new research collaborations, capacity building and the establishment of the first Cardiovascular Assessment Centre at the Biomedical Research and Training Institute in Zimbabwe, This will enable clinical assessments and research on cardiovascular disease.

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