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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

East Africa has a high burden of poverty-related infectious diseases and is at risk of outbreaks of Ebola and other viral haemorrhagic infections. The prevalence of TB, HIV/AIDS and malaria is high and co-infections are common; drug resistance is a growing threat.

Several countries in East Africa have well-established clinical research bases and strong links to European research collaborations. Networking provides opportunities to coordinate activities, share experiences, and build the capacities of less well-developed research sites. 

The EACCR was established in 2009 with EDCTP funding, initially with 17 institutions in five countries. Its core focus was on capacity building, through long-term (master’s and PhD) and short-term training, as well as strengthening of laboratory capacities. Following needs assessments, the EACCR completed infrastructure upgrades at more than 20 sites. It enabled more than 200 researchers to attend ten short-term courses, conducted a wide range of research skills workshops, and supervised 30 postgraduate research fellows. 

The EACCR also developed an innovative reciprocal monitoring scheme, generating a pool of experienced clinical trial monitors able to provide independent high-quality oversight of clinical trial activities. Trainee monitors are paired with experienced monitors so that they gain hands-on experience of clinical trial monitoring, raising awareness of quality management and increasing the pool of expertise able to perform monitoring activities in the region.  

In follow-up EACCR2 funding, the network is expanding to cover neglected infectious diseases as well as Ebola. It has grown in size, now encompassing 23 African institutions in six countries and eight European partners from five countries. EACCR is also a part of the two EDCTP-funded epidemic preparedness consortia, ALERRT and PANDORA-ID-NET.

Thematic nodes of excellence have been established for malaria, TB, HIV/AIDS and neglected infectious diseases (primarily focusing on dengue, schistosomiasis, leishmaniasis, cysticercosis and Ebola), with a cross-cutting training node. Each area has a strong focus on collection of epidemiological, entomological and clinical data that will provide necessary background information to support interventional studies.

The network is also continuing its reciprocal monitoring scheme. It has reached agreement with projects being carried out at EACCR2 institutions to carry out monitoring activities. Network members and other partner institutions have successfully applied for additional EDCTP support, for example for the EXIT-TB study which is promoting new approaches to identify cases of TB that are currently being missed. The EACCR is also supporting four PhD projects associated with the Weltel trial, exploring the impact of weekly phone messaging on retention in a prevention of mother-to-child transmission trial. 

Each node is coordinating needs assessments and upgrading of infrastructure for clinical trial sites, and exploring opportunities for development of joint research protocols, including multi-disease studies to examine the impact of co-morbidities. The network is also continuing to organise a wide range of training opportunities for researchers and research support staff at all levels.

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.

The EACCR2 project is supporting the development of clinical research capacity across a wide area in East Africa, and coordinating the development of joint multicentre research proposals. It is upgrading clinical research skills and infrastructure, and enabling a wider range of institutions to contribute to research into the poverty-related infectious diseases affecting East Africa.

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