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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

People with advanced HIV disease are at high risk of death. Cryptococcal infections are a particular challenge, accounting for up to a quarter of deaths of people with HIV.

Early screening for cryptococcal infections, followed by prompt treatment with fluconazole for those testing positive, has been shown to be a highly effective way at reducing mortality in those with advanced HIV disease. In the EDCTP-funded REMSTART trial, cryptococcal screening plus home visits for four weeks to encourage adherence to treatment reduced mortality by 28%.

Findings from this trial informed WHO guidelines on management of late-stage HIV infection in Africa. Even so, take up of cryptococcal screening and home support has been limited.

To promote greater uptake, the REMSTART team is undertaking an implementation study in Tanzania, based on a modified version of the approach used in the original REMSTART trial. Although economic analyses suggested that the REMSTART model would be cost-effective, travel for home visits represented a major proportion of the costs of the intervention and could be logistically challenging. Text messaging could represent an even more cost-effective alternative.

The TRIP study is evaluating the implementation of cryptococcal screening and fluconazole treatment plus text messaging – weekly for the first month then monthly for the next three months – at 24 rural and urban sites in Tanzania. It will generate key data on lives saved when the intervention is introduced into routine practice in these two settings, on its cost-effectiveness, and on the practical barriers to its introduction.

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 project has maintained close contact with the Ministry of Health in Tanzania and a range of implementing partners, including UNITAID’s Clinton Health Access Initiative (CHAI). The project’s experience has informed the development of a national plan for cryptococcal screening, which is now being implemented at additional sites by the Ministry of Health, CHAI (which has taken over the TRIP project’s study sites) and other implementing partners.

The project also contributed to the Global Advanced HIV Disease Toolkit, which will support the introduction of the tools evaluated by the TRIP project in other countries. Through UNITAID’s CHAI project, the intervention is already being implemented in seven countries in Africa. The project is therefore helping to reduce the burden of one of the leading causes of death in people with HIV infections.

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