“
crucial in

widening African

children’s access

to antiretrovirals

”

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

Although a large proportion of the populations of low-resource countries are infected with the TB bacterium, Mycobacterium tuberculosis (Mtb), most infections are ‘latent’ or inactive and are not treated. A key challenge in TB control is to identify those who develop active TB disease and require treatment.

Unfortunately, the clinical symptoms of TB are not specific and currently used diagnostic tools have multiple drawbacks. A molecular platform, Xpert MTB/RIF, offers relatively good performance and speedy results, but at a cost. A key priority is therefore a cheap and easy-to-use ‘triage test’ that could be used at the frontline to identify those most likely to have active TB, who could then be referred for confirmatory testing.

The SeroSelectTB project team has investigated the presence of antigens in patients with active TB and in controls, identifying a range of potential molecular markers indicative of active TB. Importantly, these markers also differentiate active TB infections in people living with HIV – a key consideration, as half of TB cases in sub-Saharan Africa are also HIV-positive.

Drawing on these findings, the project team plans to develop a simple dipstick-type diagnostic (a lateral flow assay), based on an established technology platform available in South Africa. After a trial to evaluate the new test’s performance, the project will organise a larger study to assess its impact in real-life settings – in particular, whether use of the new tool reduces diagnostic delays and leads to speedier initiation of treatment. The trial will be run in three countries with different health system settings to examine the potential impact of contextual health system factors. Cost-effectiveness will also be explored.

The goal is to develop a tool with comparable sensitivity to molecular diagnostics that could be used in initial assessments to guide further investigation. The project team includes members with expertise in regulatory approvals and, if results are positive, a dossier would be put together to support regulatory submissions and applications for WHO prequalification.

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 SeroSelectTB project aims to develop a simple, easy-to-use and affordable triage test for TB that could be manufactured in South Africa for as little as US$1. Modelling suggests that its introduction could reduce the costs of TB diagnosis by 40%, generating savings to national TB programmes of US$36m a year, while also ensuring more rapid initiation of treatment of people with active TB and reducing transmission due to missed cases.

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