“
test the safety and efficacy of this new formulation in young children

”

Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

Malaria in pregnancy (MiP) continues to be a significant public health issue, particularly in sub-Saharan Africa. The coverage of pregnant women with three or more doses of intermittent preventive treatment using sulphadoxine-pyrimethamine (IPTp-SP) is recommended to prevent risks associated with MiP in moderate-to-high transmission settings. However, the evaluation of malaria prevention strategies during pregnancy relies on the precise diagnosis of parasite and the monitoring of antimalarial resistance using genomic techniques. Recent evidence shows the emergence of a novel Pfdhps-431V mutation in Nigeria. This new mutation may further complicate existing SP-resistance.

Dr Adegbola’s project is, first, to advance his expertise in clinical research and malaria parasite genomics by attending a training at the Center for Medical Parasitology of the University of Copenhagen in Denmark. The training will enhance his expertise on techniques such as DNA isolation, PCR amplification and Sanger sequencing.

Secondly, he will conduct a clinical study of resistance to SP, specifically, he will examine to what extent dhps-431V mutation influences the protective efficacy of IPTp-SP. To this end, he will conduct a pilot study based on a small number of samples (100-150) aiming to pinpoint the trends of newly emerging mutations, design qPCR and sequencing methods, and generate a small dataset as the basis for the intended follow-on project.

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 fellow will transfer the acquired skills to his home organization and introduce the skills to other colleagues through seminars, workshops and incorporation into a postgraduate training curriculum.

Moreover, an observational study will be done among adult women attending the ante-natal clinic. This follow-on study aims to detect P. falciparum positivity at delivery as well as pregnancy outcome in participants who must have received three or more doses of IPTp_SP. The presence of existing and new Pfdhps/Pfdhfr mutations in the samples positive for P. falciparum will be determined using a quantitative PCR. The prevalence of novel Pfdhps-431V mutant and other Pfdhps/Pfdhfr resistance alleles among the study population will be estimated. The significance of the resistance genes on the efficacy of SP will be described by looking at its associations with the reported IPTp use, P. falciparum infection, maternal anaemia, low birth weight, and preterm delivery.

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