The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

Bringing antiretroviral drugs to children

“
test the safety and efficacy of this new formulation in young children

”

West Africa was badly affected by the 2014–16 Ebola outbreak, and has a high burden of poverty-related infectious diseases. Although HIV is not as prevalent as in other sub-regions, progress in prevention and rollout of antiretroviral therapy has been relatively slow.

Collaboration across research centres in West Africa is challenged by language barriers. However, several strong research institutions exist in West African countries and have established productive relationships with European partners.

The challenge

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.

The project

WANETAM was established in 2009 with EDCTP funding, initially with 14 institutions in seven countries; additional African and European partners joined later. WANETAM’s core focus was on capacity building, organising long-term and short-term training, as well as strengthening of laboratory capacities; stronger institutes in the network developed clinical trial units and secured international accreditation. 

Initial funding also provided an opportunity to establish surveillance activities to provide baseline data for future studies. These included work on physiological measures in human subjects as well as antimalarial drug monitoring.   

In follow-up WANETAM II funding, the network expanded to cover neglected infectious diseases as well as Ebola. Thematic nodes of excellence were established for each area, complemented by a cross-cutting structured training and collaboration programme.

WANETAM I provided a platform for two major international clinical trials in HIV. Progress in WANETAM II has included set up of a controlled human infection model in The Gambia, the first of its kind of West Africa. In addition, the children’s TB team set up a sub-network, the West African Paediatric TB Network (WApTBNet), which has been investigating the diagnostic accuracy of the Xpert Ultra assay. TB studies have also been mapping the epidemiology of drug-resistant TB and discussing the impact of COVID-19 on TB care and control.

Training has covered key areas including project-based training to build research leadership, hands-on clinical studies, platform development to support collaboration, and research support functions. Training has been provided for the full range of staff, including skills development and mentoring for senior staff, master’s-level online courses, and professional development courses and internships.

Training focused on three priority scientific areas: surveillance, diagnostics and resources to support clinical trial activities.

For WANETAM III, the network has grown further, now encompassing 28 institutions in 16 countries. In TB, the focus will again be on TB in children, including evaluation of novel diagnostics, and drug-resistant TB, including the potential use of whole genome sequencing in routine care. The malaria programme will explore the efficacy of malaria treatments and the effectiveness of mass drug interventions. Topics to be explored in the HIV programme will include assessment of viral load assays, development of HIV diagnostics, drug resistance and the impact of COVID-19 on HIV management.

For neglected tropical diseases, the network will be focusing on molecular diagnostic tools for helminth infections as well as the impact of mass drug administration programmes in vulnerable groups, pre-school-age children and pregnant women. A further focus will be on preparedness for emerging infections and COVID-19, including its impact on other infections.

The studies will provide a platform for embedding training of early-career researchers. The network will also aim to continue building its clinical research and laboratory capacity, as well as its data-sharing infrastructure.

To address gender inequities within clinical research, WANETAM developed a gender responsive doctoral fellowship program that would assist women overcome challenges in pursuing post-graduate training. The fellowship program known as TALENT was developed in order to create a gender sensitive platform for clinical research in WANETAM. WANETAM won a grant from UK DHSC to support this program which will train female African scientists at MSc and PhD level in PRDs, emerging infections and cross-cutting disciplines such as bioinformatics, health systems research etc. The TALENT program will also enhance female role models, the supervision and mentorship structure for Ph.D. and researcher development within WANETAM to develop globally competitive female researchers in Lusophone and under-represented countries in current capacity building and research initiatives.

Impact

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.

WANETAM is strengthening clinical research capacities across multiple West African countries, enhancing coordination of activities and helping to overcome language barriers. It will facilitate large-scale multicentre trials on the key infectious disease threats in the sub-region, and enhance coordinated and rapid responses to outbreaks of emerging diseases such as Ebola and COVID-19.