PROJECT SUMMARY/ABSTRACT
This award will allow Dr Clifford George Banda to characterise the pharmacokinetic and
safety profiles of two long-acting artemisinin partner drugs, lumefantrine and amodiaquine
and their active metabolites when administered as artemether-lumefantrine plus
amodiaquine (ALAQ) in African young children with uncomplicated severe acute malnutrition
as well as adults living with HIV and on dolutegravir-based antiretroviral therapy. Dr Banda,
Malawi’s first medical specialist in Clinical Pharmacology and Therapeutics, will further his
career development by;1) gaining skills in early phase clinical trial design and conduct in
complex subpopulations; 2) consolidating skills in clinical translation of quantitative
pharmacology (population pharmacokinetic-pharmacodynamic modelling) to inform dose
optimisation of antimalarials in the two key target subgroups of children with severe acute
malnutrition and adults living with HIV; and 3) strengthening his clinical and research
leadership skills to allow transition into research career independence. In the proposed
project work,he hypothesises that severe acute malnutrition is associated with reduced
absorption and subsequent bioavailability of lumefantrine, amodiaquine and their active
metabolites. Consequently, the attained concentrations would be insufficient to treat and
prevent malaria recurrence. He will study the effect of uncomplicated severe acute
malnutrition on lumefantrine and amodiaquine exposure. Furthermore, there are concerns
about a potential reduction of dolutegravir exposure when amodiaquine is co-administered
with dolutegravir-based antiretroviral therapy, Dr Banda will characterise the effect of ALAQ
on dolutegravir overall exposure in adults living with HIV. This evidence is needed to inform
the optimal dosing of the promising triple antimalarial combination, ALAQ, in these two
subpopulations. It would support the World Health Organisation’s strategy for responding to
antimalarial resistance in Africa by identifying innovative ways to combine and repurpose
existing antimalarial therapies as a tool to delay antimalarial resistance while awaiting the
development and licensing of novel non-artemisinin-based combination therapies.
