“
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

Globally, one in four people are infected with the TB bacterium. Of these, 10% go on to develop active TB disease. One key TB control strategy is to target groups at high risk of progression to active TB disease, and highly effective preventive treatments have been developed.

Vulnerable groups include people with diabetes, who are nearly four times more likely to develop TB, especially if their diabetes is uncontrolled. They also suffer worse symptoms, more treatment failures, and a higher risk of death. An estimated 629 million people are likely to develop diabetes by 2045, 90% of them in low- and middle-income countries. Around 7% of people in sub-Saharan Africa currently have diabetes, although 70% of cases are undiagnosed. The numbers affected in the region could reach 41 million by 2045, a 156% increase (compared with a global increase of 48%).

The PROTID project aims to determine whether preventive treatment of TB in people with diabetes is beneficial and cost-effective. It is the first ever large-scale randomised controlled trial of preventive treatment of TB in people with diabetes.

A total of 6,000 people will be recruited in Tanzania and Uganda, countries with high TB burdens, and randomised to placebo or a 12-week course of a standard preventive regimen, rifapentine and isoniazid. They will then be followed for two years to examine progression to active TB disease and the severity of symptoms.

The project will also investigate different approaches for screening for TB in people with diabetes, ways to better improve the care pathway, including coordination of TB and diabetes care, and the cost-effectiveness of preventive TB treatment in this group.

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 PROTID project will generate evidence that could have a major influence on global policy and practice. People with diabetes are already thought to account for more than 10% of the spread of TB, a figure that is projected to rise as the number of cases of diabetes increases. Overall, 15–30% of the global TB disease burden may be attributable to diabetes. If preventive treatment is found to be effective in people with diabetes, this would benefit large numbers of people with a chronic health condition but also reduce the transmission of TB – the PROTID project team estimates that preventive treatment in people with diabetes could prevent 11% of cases and 13% of TB-associated morbidity.

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