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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

Prevention of mother-to-child transmission has markedly reduced the number of infants with HIV infections. However, a million infants are exposed to HIV in sub-Saharan Africa each year, and this exposure appears to have harmful impacts on their health. For example, they are at greater risk of other infections, including lower respiratory tract infections, malaria and diarrhoeal disease, which account for more than 40% of childhood deaths.

There is some evidence that the BCG vaccine for TB has non-specific immune stimulatory effects that protect against other infections. In addition, the timing of BCG vaccination might also influence its ability to stimulate immune responses – later vaccination could generate more powerful immune responses but might leave infants vulnerable in the high-risk period before vaccination. Furthermore, most data are from observational studies rather than well-controlled clinical trials.

In her Senior Fellowship, Dr Victoria Nankabirwa aims to generate rigorous clinical trial data on the protective effect of BCG vaccination on serious infections in HIV-exposed infants.  Dr Nankabirwa has been running a clinical trial comparing the risk of serious infections in infants receiving BCG vaccine either within 24 hours of birth or at 14 weeks. Because the number of infections has been much lower than anticipated at study sites, the number of infants recruited needs to be doubled, which will be facilitated by EDCTP fellowship funding.

Dr Nankabirwa is an experienced clinical researcher who has worked in the UK, USA and Bangladesh, as well as at WHO headquarters in Geneva. She is committed to developing up and coming talent and is Director of the Distance Education Master of Public Health programme at Makerere University in Uganda. Through her fellowship, she plans to establish an innovative ‘clinical trials teaching clinic’ – the first of its kind in the region – to provide hands-on training for graduates and post-graduates within the context of ongoing clinical trials. The clinic will help to bridge the gap between the mainly theoretical teaching that students currently receive, enabling them to apply their learning in a practical context.

During her fellowship, Dr Nankabirwa will directly supervise at least five graduate students and at least three PhD students. She will also be developing an online graduate-level course on randomised controlled trial methodology for low-resource settings, which will contribute to clinical research capacity development across the whole of sub-Saharan Africa.

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.

Dr Nankabirwa’s research will provide rigorous trial data on an important but controversial area of medicine, the potential non-specific effects of BCG. The results will have immediate public health relevance and the potential to shape national vaccination policies. In addition, her educational initiatives will play an important role in developing clinical research capacity in the region.

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