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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

Sleeping sickness progresses in two stages, the early stage with parasites in blood and the late stage in which parasites invade the central nervous system. Drug treatment for both early- and late-stage disease differs. Therefore, it is mandatory to first determine the disease stage.

However, the current staging criterion using cerebrospinal fluid relies on an invasive lumbar puncture that is also required to monitor treatment efficacy. Since initial disease diagnosis is done using blood, identification of plasma biomarkers to replace current criteria for the evaluation of stage and treatment efficacy is of utmost urgency. The challenge is to establish the clinical utility of several plasma biomarkers.

Previously, novel plasma biomarkers were identified with proteomics methods. The markers discriminate late stage from early-stage patients for Trypanosoma brucei rhodesiense. The clinical utility of these biomarkers is not yet known and it is not clear if these markers would also apply to T. b. gambiense.

In this study, Dr Kato and his team propose to carry out a clinical validation of these novel plasma biomarkers as stage diagnostic markers. We shall conduct a retrospective study using archived samples from the trypanosomiasis biobank at Makerere University to assess disease staging potential. Patient samples will be selected that were recruited at Lwala hospital (North Eastern Uganda) for T. b. rhodesiense, and Omugo (West Nile) for T. b. gambiense. Through proteomics methods, he aims to find out whether markers identified for T. b. rhodesiense also apply to T. b. gambiense. Clinical validation of identified markers will involve analysis as a single biomarker and as a panel of two or more analytes to determine the best predictor of late-stage disease.

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.

Successful identification of biomarkers will form a basis for translation into field-based dipstick assays for disease staging and inform policy regarding disease staging. This will greatly improve patient management through the abolition of the mandatory requirement of an invasive lumbar puncture which is painful to patients.

Furthermore, the successful execution of this project will build capacity at Makerere University by offering training of critical skills to junior researchers.

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