“
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

TB kills more than 1.5 million people every year. Standard treatment involves six months’ use of multiple antibiotics. In addition, multidrug-resistant TB is on the rise – nearly half a million cases were reported in 2016 – and requires even longer and more arduous treatment, with only a 50% chance of cure.

Shortening and simplifying TB drug treatments are major goals in TB research. Shorter regimens would cost less, be easier to implement and easier for patients to manage.

The development of highly effective new drugs – particularly bedaquiline and pretomanid – is raising hopes that shorter duration treatments are a realistic possibility.

A recent trial which showed that bedaquiline and pretomanid, combined with two potent currently used drugs (moxifloxacin and pyrazinamide), cleared TB bacteria from the lungs of patients with multidrug-resistant TB up to three times faster than the standard regimen cleared bacteria from patients with drug-sensitive TB – the fastest rate of clearance ever seen in a clinical trial. Following up these positive findings, the Simplici-TB trial is now comparing a four-month course of the new combination to treat drug-sensitive TB and a six-month course to treat multidrug-resistant TB.

The study is being run in partnership with the TB Alliance, a US-based not-for profit organisation, with the African studies forming part of a wider global trial evaluating the new combination.

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 Simplici-TB will provide key data on a highly promising new combination treatment for TB. It could accelerate the introduction of a treatment that has a major impact on treatment of both drug-sensitive and drug-resistant TB in sub-Saharan Africa.

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