Efficacy, safety and pharmacokinetic exposure of artemether lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in HIV infected Malawian children on antiretroviral treatment
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Date
2021-03-17
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Kamuzu University of Health Sciences
Abstract
Type of research study: A prospective observational study will recruit and follow up two groups of
children aged between 6 months and 16 years diagnosed with uncomplicated malaria in Lilongwe
district. One group will be HIV infected and on antiretroviral treatment and another one will be HIV
uninfected.
The problem: 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 subpopulations
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. WHO
recommends countries to evaluate efficacy of their first-line antimalarial drugs at least once every two
years. Since these studies are done in HIV negative children, there is an important need to assess the
efficacy of first-line antimalarial drugs in HIV infected children on ART as well.
Objective: This study aims to evaluate the efficacy and safety of artemether lumefantrine (AL) for the
treatment of uncomplicated P. falciparum malaria in HIV infected and HIV uninfected children in
Lilongwe, Malawi.
Methodology: A prospective observational study of antimalarial efficacy will be conducted in a total of
71 HIV-malaria coinfected children on ART and 141 HIV uninfected children with confirmed malaria
who meet the inclusion criteria. Once enrolled, participants will be given AL for treatment and
followed up for 28 days. The follow up will consist of fixed schedule of visits (at Day 1,2,3,7,14,21 and
28) with 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 AL.
PCR analysis will be used to distinguish between recrudescence and reinfection. On day 7, post
treatment initiation, a blood sample will be collected to quantify lumefantrine concentrations, as a
predictor of overall lumefantrine exposure. These concentrations will be correlated with AL treatment
efficacy. The design has adapted some procedures of the recommended WHO methods for surveillance
of antimalarial drug efficacy.
Expected findings and their dissemination: This study is designed to generate the information required
to assess whether AL is efficacious in HIV infected children on ART. It is anticipated that the study
results will improve the management of malaria in HIV infected children on antiretroviral drugs in areas
affected by both HIV and malaria. This study will also provide information on the pharmacokinetics of
AL and its efficacy that would contribute to the development of appropriate approaches/options for
optimal effectiveness of the treatment. The findings of this study will be published in peer-reviewed
journals and shared with all relevant stakeholders.
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Research Subject Categories::MEDICINE