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

PI/Fellow: Prof Pauline Byakika-Kibwika

This is a Senior Fellowship by Associate Professor Pauline Byakika-Kibwika whose aim is to generate data to guide optimization of 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 or dolutegravir. Previous studies 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. 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. 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.

The study protocol was approved by the IDI Scientific Review committee, Makerere University School of Medicine Research Ethics Committee, the Uganda National Council for Science and Technology and the National Drug Authority. Administrative approval was provided by Tororo District Hospital and the trial was registered in the clinical trials registry. Study participant screening and enrolment for the safety and pharmacokinetics studies was completed at the IDI site. The second trial site was set up in Tororo hospital and 20% participants have been enrolled. Enrolment and follow-up of participants is ongoing.

This Fellowship has provided support for the Senior Fellow, Associate Professor Pauline Byakika-Kibwika to transform into Professor of Medicine and an African Research Leader in Clinical Trial research and related activities, through among other criteria, scientific publication, mentorship and training of junior scientists. She has recruited one PhD candidate (Alex Mwesigwa) who has been admitted at Makerere University. The PhD candidate’s concept was approved by the School of Medicine Higher Degrees Ethics and Research Committee. Under guidance of Pauline and the other supervisors, Alex has developed the PhD research proposal which was reviewed and approved by the same committee. The PhD objectives focus on evaluating the Plasmodium falciparum genetic diversity, multiplicity of infection, gametocytemia, and recrudescence.
Pauline recruited, mentored and supervised 6 Masters’ students, 4 of whom completed and graduated with a Masters in Medicine in Internal Medicine, and 2 are soon completing the Master of Science in Clinical Epidemiology and Biostatistics.