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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

Effective monitoring of clinical trials requires that systems are in place to monitor and investigate potential medical safety issues. Such pharmacovigilance activities are also essential when new drugs are introduced and are used by greater numbers of people.

However, many national regulatory agencies in sub-Saharan Africa, which have responsibility for drug safety, lack the expertise, critical mass and infrastructure to monitor drug safety effectively during clinical trials and after licensing.

The PAVIA project is developing a model for strengthening of pharmacovigilance systems in four sub-Saharan African countries – Eswatini, Ethiopia, Nigeria and Tanzania – based on enhanced cross-sectoral collaboration. It is helping to build bridges between disease-focused public health programmes, national regulatory agencies and medical research institutions. This triangular arrangement will create a channel for identifying and investigating potential safety signals, with medical research institutions acting as a source of clinical expertise.

Capacity at national pharmacovigilance centres will be gradually developed, focusing on data collection, analysis, safety signal identification and investigation. The model is being developed with an initial focus on multidrug-resistant TB. A blueprint will be developed to facilitate extension of the model to other national public health programmes, such as those for malaria and HIV, and potentially adoption by other countries. 

National assessments have been undertaken to identify development priorities and to inform country-specific and locally owned capacity-development roadmaps. The project will also work with local ministries of health and other key stakeholders to emphasise the critical importance of pharmacovigilance. Early progress has included the creation of ‘pharmacovigilance triangles’ in each country to enhance coordination across different agencies.

In addition, the project has established an international advisory board to ensure coordination and alignment with regional and global pharmacovigilance initiatives. Links have been established with the EDCTP-funded PROFORMA project, which has similar aims, with the EXIT-TB project and with the East African Network of Excellence (EACCR2). It has also engaged with the African Union Development Agency, AUDA-NEPAD, to promote wider policy coherence.

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 PAVIA project will establish a collaborative cross-sectoral model for pharmacovigilance, with clear roles and responsibilities, as well as enhanced national infrastructures for reporting of drug safety data. With an initial focus on TB, by identifying enablers and barriers to implementation, it will facilitate the expansion of pharmacovigilance systems to other disease areas. In doing so, it will enhance the capacity of health systems to absorb new interventions for poverty-related infectious diseases.

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