Pharmacokinetics of selected antiretroviral and antimalarial drugs in Ugandan adults

Abstract

Human immunodeficiency virus (HIV) and malaria are two major infectious diseases causing significant morbidity and mortality worldwide. The two have overlapping geographical distribution in sub-Saharan Africa, where over 90% of the world malaria burden and 68% of the global HIV burden occur. Infection with HIV increases risk of malaria infection Severe malaria and death occur with higher frequency in HIV-infected individuals. There has been a roll-out of antiretroviral therapy (ART) for HIV treatment and artemisinin-based combination therapy (ACT) for malaria treatment. To facilitate ART scale-up, less expensive generic ART formulations are widely prescribed. While these facilitate rapid scale-up, their quality and bioequivalence need to be monitored to ensure long term success of ART regimens. Highly active ART is a combination of at least three active antiretroviral drugs from at least two different pharmacological classes. Combination therapy has potential for pharmacokinetic drug-drug interactions which may result in high plasma drug concentrations causing excessive toxicity or sub-therapeutic concentrations leading to treatment failure with risk for development of resistance. Treatment of HIV-malaria co-infected patients receiving ART with ACT creates potential for drug interactions. This thesis presents a series of intensive pharmacokinetic studies evaluating the pharmacokinetic profiles and drug interactions of some ART and artemether-lumefantrine (AL) which is the first-line ACT in Uganda and a description of the pharmacokinetic profile and clinical response to intravenous (IV) artesunate.