Efficacy, safety and pharmacokinetics of artemether lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in HIV infected Malawian children on antiretroviral treatment

There is paucity of consolidated evidence to guide optimisation of the current arsenal of drugs that are used to fight malaria in individuals co-infected with HIV especially in key at-risk sub-populations such as children. Potential drug-drug interactions between antimalarial drugs and antiretroviral therapy (ART) raise concern in the control of malaria in children who are co-infected with HIV.  Artemether-lumefantrine (AL) is a commonly used artemisinin-based combination therapy (ACT)  in most malaria programmatic settings but there is limited understanding of its efficacy in malaria  and HIV co-infected children in light of the potential drug-drug interactions between ACTs and ART. This study aims to assess the efficacy and safety of AL  in treating uncomplicated Plasmodium falciparum malaria in HIV infected children on standard ART in Malawi and explore ways to integrate such findings in informing policy and treatment guidelines.  Methods: A prospective evaluation of antimalarial efficacy will be conducted in 140 HIV infected children on ART and 140 HIV uninfected children with uncomplicated malaria who meet the study inclusion criteria. Participants will receive  AL  and monitored for 28 days. The follow-up will consist of a fixed schedule of visits and corresponding clinical and laboratory examinations. The proportion of participants experiencing therapeutic failure during the follow-up period will be used to estimate the efficacy of the study drug.  A-subset of the study population comprising of 50 participants will participate in a pharmacokinetic analysis of AL. A systematic application of a knowledge translation strategy to engage with policy and decision makers in the research process will be done with the aim of overcoming the disconnect between primary research and utilisation of findings for policy and practice decisions.  Relevance of this application to the call: The study addresses two of the poverty related diseases which include HIV/AIDS and malaria listed as part of the EDCTP2 programme. In addition, the focus on HIV infected children contributes towards the achievement of sustainable-development-goal number 3 which aims at ensuring healthy lives and promotion of well-being for all age groups. The findings from this study will help in optimising the use of the recommended first line malaria treatment for all as most antimalarial efficacy studies are conducted in HIV uninfected populations.  This fellowship will equip the fellow with the necessary experience to develop into an independent researcher as well as become a research  leader in sub- Saharan Africa.

Project information

Drug-based Strategies
Vulnerable Populations

Nov 2020 — Oct 2023

$170,000

Malawi