Project: Optimizing Malaria Treatment for HIV-Malaria co-infected Individuals by Addressing Drug Interactions between Artemisinin-based Combination Therapies and Antiretroviral Drugs

Acronym	OPTIMAL (Reference Number: TMA2017SF-1943)
Duration	01/04/2019 - 30/03/2024
Project Topic	Background: Malaria and HIV have significant interactions at various levels; the geographical and epidemiological overlap increases risk for co-infection and co-treatment, HIV immunosuppression increases malaria incidence, parasitaemia, severity and risk for poor treatment outcomes including mortality and adverse pregnancy outcomes such as anemia and low birth weight. Malaria infection increases HIV viral replication and viral load. Both malaria and HIV are treated with combination therapy to enhance treatment outcomes and reduce risk for development of resistance, consequently creating potential for drug-drug interactions (DDIs) when the two diseases are treated concomitantly. Problem statement: Previous studies conducted by my study team and researchers elsewhere, demonstrated significant reduction in systemic exposure to artemether, its metabolite dihydroartemisinin, and the long acting partner drug lumefantrine when the ACT artemether-lumefantrine was co-administered with efavirenz-based ART. Justification: These findings are important because sub-therapeutic concentrations of anti-infectious drugs increase risk of treatment failure and development of drug resistance yet there are few drug options available for both malaria and HIV treatment especially in the malaria endemic regions. Despite these findings, there is very scanty data to demonstrate effects of these interactions on malaria clinical outcomes and no guidance on therapeutic interventions to overcome these deleterious effects of drug interactions. Data are therefore urgently needed to optimize treatment of malaria for HIV-malaria co-infected individuals to improve treatment outcomes and prevent emergence of resistance to antimalarial drugs. Methods: We aim to train and conduct a Randomised Clinical and Pharmacokinetic Trial to generate data to optimize malaria treatment for individuals co-infected with HIV and malaria, by utilizing innovative interventions to overcome the significant drug interactions between artemether-lumefantrine and efavirenz. The proposal fits within the scope and objectives of EDCTP and call topic description which highlights the shortage of senior researchers and research mentors in sub-Saharan Africa in the field of poverty-related diseases. This Fellowship will provide support for the Senior Fellow to transition into an African Research Leader in Clinical Trial research and related activities. The Senior Fellow will gain leadership experience and skills to train and mentor junior scientists in sub-Saharan Africa. She will train and mentor 1 PhD and 1 Master’s Degree student to completion with additional mentorship for them to join Makerere University Faculty thus ensuring sustainability and institutional capacity development. She will utilize this Fellowship exposure and experience to strengthen research collaboration and attract additional research funding for Makerere University.
Network	EDCTP2
Call	Senior Fellowships 2017

Project partner

Number	Name	Role	Country
1	Infectious Diseases Institute Limited	Coordinator	Uganda