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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

In low- and middle-income countries (LMICs), oral vaccines perform poorly. Several reasons are postulated including maternal breast milk components, environmental enteropathy, nutritional factors, and intestinal infections. Zambia has had a high burden of cholera over the past several years and the government is deploying a new oral cholera vaccine (Shanchol™).

While the vaccine has good efficacy in clinical trials, its real-world immunogenicity is unproven.

For example, the duration of vaccine-induced immune response not well-characterised in LMICs where cholera outbreaks are common. The impact of human genetic predisposition on susceptibility to cholera on vaccine responses is unknown and so is the impact of HIV infection on the functional immune protection. Therefore the challenge is to evaluate the vaccine in real-world settings, specifically in Zambia.

In collaboration with local health officials and scientists in Zambia, the study proposed to leverage the introduction of Shanchol in Zambia to address the following research objectives. First, she profiled the cholera-specific antibody status of a population at risk of cholera before and after receiving 1st and 2nd dose of Shanchol oral cholera vaccine (OCV). Secondly she developed and evaluated a non-invasive proxy measure of OCV immune responses. Thirdly and fourthle, Dr Chisenga measured the effect after immunising HIV-infected individuals through measurement of the OCV-generated antibodies, and assessed the impact of ABO blood groups on cholera antibody generation.

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.

Valuable information on the cholera vaccine efficacy in real-world Zambian settings has been acquired in the context of Zambian health policy. Dr Chisenga also gained new research (laboratory) skills and took a grant writing course at Johns Hopkins University in the U.S. The study established Dr Chisenga as a leader in immunology research in Zambia and prepared her to compete for further peer-reviewed research funding.

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