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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

More than 500,000 new cases of multidrug-resistant (MDR) TB occur each year, around 10% of which are extremely drug resistant (XDR) TB. Namibia is classified as a high TB burden country, with 11,000 new cases a year; 3.9% of new cases and 8.7% of previously treated cases are MDR-TB.

It is vital that cases of drug-resistant TB are identified in a timely fashion, so that patients can be started on the most appropriate treatment but also to limit the spread of drug-resistant strains. This requires an active case-finding strategy – going out into the community to identify cases rather than waiting them to appear at health facilities.

In her Senior Fellowship, Dr Mareli Claassens aims to develop a clearer picture of drug-resistant TB in Namibia, to investigate the feasibility of targeted case finding to improve TB control, and to develop a TB transmission model to explore the potential impact of case-finding interventions.

Her work will focus on two areas of Namibia thought to be hotspots for transmission of drug-resistant TB, including disadvantaged ethnic minority populations. A wide range of clinical, epidemiological, laboratory and social networking data will be collected to characterise drug-resistant TB cases in these regions and how they are being spread. Through a collaboration with Research Center Borstel in Germany, this work will take advantage of the power of whole genome sequencing to reveal pathways of transmission of drug-resistant TB strains.

These results, plus a systematic review of the literature, will be used to identify a potential strategy for active case finding. Interventions will be tested in a feasibility study focusing on transmission hotspots, households and hospitals.

Data from the drug-resistant TB mapping exercise and from Namibia’s national TB programme will feed into a model of drug-resistant TB transmission, which will be used to explore the potential impact of case-finding interventions. This strand of work will include a health economic component to provide data on the likely cost-effectiveness of targeted case-finding interventions.

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.

Dr Claassens’ research will generate a deeper understanding of drug-resistant TB in Namibia and establish the feasibility and likely costs of locally appropriate case-finding interventions. The findings will contribute to more effective control of drug-resistant TB in Namibia. In addition, it will build local capacity in whole-genome sequencing and further develop Dr Claassens’ research career, facilitating her addition to the faculty at the University of Namibia.

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