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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

Respiratory diseases, including TB and lower respiratory tract infections, are major causes of death and ill-health in sub-Saharan children. In addition, it is increasingly recognised that damage to the lungs in childhood increases the risk of TB and other lung diseases in later life.

Cohort and other clinical studies are generating a wealth of data on infectious diseases and risk factors affecting vulnerability to infection or the likelihood of long-term impacts. However, making full use of these data requires expertise in biostatistics, so new approaches to data analysis can be applied.

With a background in biostatistics and modelling, Professor Lesosky has a particular interest in the development of biomarkers to predict disease progression, particularly in TB. It is highly unlikely that single markers will be informative of disease progression, and complex statistical analysis is likely to be needed to dissect complex biological data to identify predictive patterns across multiple markers.

In her EDCTP Senior Fellowship, Professor Lesosky is developing new methods to extract information on key factors affecting childhood lung health. Her work will draw on two ongoing studies that are exploring the longitudinal determinants of TB and lower respiratory tract infections in African children. She is aiming to develop new approaches that will shed light on how factors such as interactions between pathogens, household and environmental pollution, and clinical and demographic factors affect the risk of TB and lower respiratory tract infections.

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 Lesosky’s Senior Fellowship project will provide new insight into the origins of common and important lung infections in children, supporting more effective prevention and identification of those at risk of disease. By training two PhD students and four Master’s students, her project will also build capacity to analyse and extract more information from complex biological datasets.

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