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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 Global Program for the Elimination of Lymphatic Filariasis has been operational since 2000 with 5-6 rounds of effective annual mass drug administration (MDA). The treatment regimen is ivermectin (IVM) in combination with diethylcarbamazine (DEC) or albendazole (ALB). The objective is to eliminate the disease by 2020,

In Ghana, MDA has been done since 2001. While the disease has been eliminated in many areas, its transmission has persisted in some implementation areas that had experienced 15 or more rounds of MDA. In some settings of high transmission intensity, alternative intervention strategies, including twice-yearly MDA and sleeping under insecticidal nets, have significantly accelerated transmission interruption. The challenge is to identify new intervention strategies that eliminate the residual infection in areas of persistent transmission and speed up the LF elimination process.

Two cluster randomised trials will be implemented in LF endemic communities in Ghana. The interventions will be yearly or twice-yearly MDA delivered to entire endemic communities. Allocation to study group will be by clusters identified using the prevalence of LF. Clusters will be randomised to one of two groups: receiving either (1) annual treatment with IVM+ALB; (2) annual MDA with IVM+ALB, followed by an additional MDA 6 months later. The primary outcome measure is the prevalence of LF infection, assessed by four cross-sectional surveys. Entomological assessments will also be undertaken to evaluate the transmission intensity of the disease in the study clusters. Costs and cost-effectiveness will also be evaluated. Among a random subsample of participants, microfilaria prevalence will be assessed longitudinally. A nested process evaluation, using semi-structured interviews, focus group discussions and a stakeholder analysis, will investigate the community acceptability, feasibility and scale-up of each delivery system.

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.

Establishing an acceptable, feasible and cost-effective alternative intervention strategy (i.e. biannual treatment of LF endemic communities) to support the Global Program for the Elimination of Lymphatic Filariasis, would accelerate the interruption of LF transmission.

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