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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

The 2014–16 Ebola outbreak, which claimed the lives of at least 11,000 people, illustrated the devastating impact of emerging infections. Recently, African has experienced multiple other outbreaks, including yellow fever, plague and Ebola-related viral infections. In addition, given the growth in international air travel, Africa is at risk of importing emerging infections from other regions, such as Middle East respiratory syndrome coronavirus (MERS-CoV). Finally, there is an ongoing risk that entirely new infections will jump species from animals to humans, with potentially devastating consequences.

Central to the control of emerging and re-emerging infections is early detection and rapid response, to treat those affected and to initiate measures to halt further spread of infection. Countries therefore need to be prepared for outbreaks, with effective epidemiologic surveillance for infections and mechanisms in place for rapid responses when new outbreaks are detected. As infectious diseases are no respecters of national borders, international cooperation is essential.

PANDORA-ID-NET is a major new international consortium that is strengthening outbreak response capabilities across Africa, in partnership with national governments and other key stakeholders in Africa and Europe. Given the intimate relationship between humans, livestock and wild animals, and the potential for transmission through animal and environmental reservoirs, the consortium has adopted a ‘one health’ approach, with key input from both human medicine and veterinary science.

Its work with national governments and public health bodies will promote a wider awareness of the importance of infectious disease control and outbreak preparedness. It is establishing rapid response teams that can be mobilised within days in all four African regions. It is also developing capacity for research on emerging infections, before and during outbreaks.

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.

PANDORA-ID-NET has already been called into action, following a formal request from the Republic of the Congo for help with control of an Ebola outbreak in 2018. The consortium provided advice on local surveillance activities and diagnostic tools, and organised training on the rapid and rigorous review of research proposals in emergency situations. In the longer term, together with a complementary EDCTP-funded initiative, the African Coalition for Epidemic Research, Response and Training (ALERRT), PANDORA-ID-NET will help to ensure that African regions are better prepared to prevent, respond to and minimise the impact of infectious disease outbreaks.

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