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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

Genetic factors can have a significant impact on responses to drugs – predisposing to harmful side effects or affecting the efficacy of standard dosing regimens. Greater attention to genetic factors is ushering in an era of ‘precision medicine’, with treatments more tailored to patients’ genetic make-up.

Africa is the most genetically varied continent on Earth, yet relatively little is known about how genetic diversity in Africa affects drug responses. Notably, genetic factors affecting drug responses may be unique to Africa, emphasising the importance of research in African settings.

Professor Collen Masimirembwa is one of Africa’s leading experts in pharmacogenomics. Following his scientific training, he spent 10 years working in industry in Europe before returning to Africa. He set up the African Institute of Biomedical Science and Technology to promote drug discovery and drug development in Africa. In 2018, Professor Masimirembwa was awarded the HUGO African Prize for his contribution to genetics in Africa.

Professor Masimirembwa carried out some of the earliest pharmacogenomics studies in Africa, identifying genetic factors influencing responses to anti-parasitic drugs and antiretrovirals, including African-specific variants of drug-metabolising enzymes. His work has important implications for the safe use of the antiretroviral drug efavirenz.

In his Senior Fellowship project, Professor Masimirembwa will be building on this unique experience to develop new training schemes and research opportunities in pharmacogenomics for early-career researchers. Building on existing and new international links, he is establishing a five-week course in clinical pharmacogenomics and an 18-month master’s course in genomic medicine, in association with the University of Zimbabwe. The project will also support the training of two PhD students in the field of pharmacogenomics in the treatment of HIV and schistosomiasis.

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.

Professor Masimirembwa’s Senior Fellowship will enable him to establish a platform for the training of the next generation of pharmacogenomics researchers in Africa – a field that will become increasingly important as more insights are gained into the genetic diversity of African populations and their implications for drug responses. A new master’s programme will be established at the University of Zimbabwe during the fellowship, to ensure sustainability and continuity of training for young researchers.

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