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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

Some 350 million worldwide, mostly society’s poorest, are at risk of the single-celled parasite Leishmania. In the most severe cases, Leishmania migrates deep within the body, causing a potentially fatal condition known as visceral leishmaniasis or kala azar. Effective drugs are now available to treat kala azar, but patients may respond by developing a disfiguring chronic skin condition, post-kala azar dermal leishmaniasis (PKDL).

PKDL can have a dramatic effect on quality of life, particularly of women and children. In addition, it may provide a reservoir of Leishmania that can be transmitted to others, thwarting attempts at eradication.

The PREV_PKDL study will determine whether a newly developed vaccine, which stimulates immune responses known to be lacking in PKDL patients, is able to clear PKDL infections. The team will carry out a trial in Sudan on people who have been cured of visceral leishmaniasis by drug treatment. They will test the safety and efficacy of a single dose vaccination in preventing PKDL.

In addition, the team will work with an East African network, the Leishmaniasis East African Platform, to characterise the immune response to Leishmania and in response to drug treatments. Such studies should reveal why some patients are at risk at developing PKDL, and whether any immune responses can be used as markers to detect those at risk so they can be vaccinated.

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 PREV_PKDL trial will provide data on the safety and efficacy of the new vaccine, and whether a large phase III trial would be justified – a key step in its clinical evaluation. The study will also help to develop the capacity of East African countries in immunology research, enhancing their ability to carry out research on poverty-related neglected infectious diseases.

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