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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

The tissue-dwelling parasitic worm Onchocerca volvulus produces millions of tiny larvae (microfilariae), which live in the skin but can also invade the eye. Inflammatory reactions cause skin conditions and, in the eye, loss of sight – ‘river blindness’. Around 200 million people are at risk of infection, nearly all of them in 31 African countries.

Use of ivermectin in mass drug administration campaigns has had a major impact on disease burden. However, better treatments are required to support full elimination.

In 2018, the US Food and Drug Administration (FDA) approved moxidectin – the first new treatment for river blindness in 20 years. In trials in Africa, moxidectin was much better than ivermectin at clearing microfilariae from the skin and had longer-lasting effects, owing to its significantly longer half-life in the body.

FDA approval of moxidectin was for single-dose use in people 12 years old and older. However, for use in mass drug administration campaigns, moxidectin would have to be used repeatedly and in children under the age of 12 years. The MoxiMultidoseMod study is comparing the safety and efficacy of moxidectin and ivermectin given annually or every six months over three years. Additionally, the study is gathering more safety data on the use of a single dose of moxidectin.

It will also undertake safety and pharmacokinetic studies to assess moxidectin usage in 4–11-year-olds. And it will carry out modelling analyses to compare the time to disease elimination and cost-effectiveness of campaigns based on use of either moxidectin or ivermectin.

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.

Moxidectin could accelerate Onchocerca elimination in countries that have lagged behind in parasite control and in fragile settings where regular mass drug administration campaigns are difficult to organise. The project will provide policymakers with key evidence on the comparative advantage of moxidectin, which could be introduced using existing mass drug administration infrastructures.

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