Eleni Aklillu

I am a Professor of Tropical Pharmacology, senior researcher, and research group leader at the Department of Global Public Health, Karolinska Institutet.

My main area of research is Tropical Pharmacology, which is clinical pharmacology research focusing on major infectious diseases classified as public health problems, the most significant global burden, and the leading cause of death/disability, particularly in low and middle-income countries. My research projects address global public health issues, including maternal and child health problems, mainly in Sub-Saharan Africa, where the disease burden is paramount, and yet little is known about the impact of host-genetic factors, drug interactions, coinfections and comorbidity, and nutrition on both the safety and efficacy of therapy. My research group projects are designed to fill knowledge gaps and provide evidence-based recommendations for global and national policymakers.

Over the past two decades, my research group has investigated the impact of pharmacogenetic and environmental differences on drug metabolism and treatment outcomes in a range of communicable and non-communicable diseases, including HIV, TB, malaria infections, and Neglected Tropical Diseases, specifically lymphatic filariasis, schistosomiasis, soil-transmitted helminths and onchocerciasis and breast cancer in genetically diverse black-African populations.

Co-infections and disease comorbidities influence the treatment outcomes (safety and efficacy) in sub-Saharan Africa, where TB-HIV, HIV-malaria coinfections, and comorbidity with neglected tropical diseases are common. Concomitant therapy in co-infected patients is challenging due to drug-drug interaction, pill burden, overlapping toxicities, and adherence problems. We have conducted several prospective observational studies, randomized clinical trials, drug interaction, and dose optimization studies focusing on major public health problems, including treatment of the three most deadly infectious diseases (HIV/AIDS, tuberculosis, and malaria), neglected tropical diseases and antimicrobial resistance that claim millions of lives worldwide, especially in low-income countries.

We have conducted several major clinical trials, pharmacogenetics, pharmacokinetics, pharmacodynamics, drug interaction studies, biomarker discovery, and validation studies for drug-induced liver injury, antimicrobial resistance, and Hospital-acquired infections; pharmacovigilance and postmarking surveillance involving mass drug administration and immunization in resource-limited countries.

I have received several major external research grants in competition as a principal investigator from various national and international research funding agencies, including the European Union/Horizon-2020 via the European and Developing Countries Clinical Trials Partnership (EDCTP), the Swedish Research Council, and the Swedish International Development Cooperation Agency (Sida).

My research projects and external funding has created opportunities for 23 PhD students at Karolinska Institutet, and > 150 original research publications in peer-reviewed scientific journals. So far I have supervised 16 PhD students to completion and am still supervising 7 PhD candidates at Karolinska Institutet.

Currently, my research group is coordinating two multi-national EDCTP-funded projects entitled PROFORMA (http://proforma.ki.se) and PREGART projects (https://www.pregart.eu/), where researchers from 12 partner institutions in Ethiopia, Kenya, Tanzania, Rwanda, Uganda, The Netherlands, Italy, and Sweden are collaborating.

From 2016 - 2022, I served as a member of the committee for development research at the Swedish research council and from 2014 -2018 as vice-chair and member of the scientific advisory board for the European and Developing Countries Clinical Trials Partnership (EDCTP). Since 2021 I have been a member of the Scientific working group for WHO-TDR.

Education
- Five-year postdoctoral training in clinical pharmacology, Karolinska Institutet
- PhD degree in molecular genetics (2003) from Karolinska Institutet.
- MSc degree in biochemistry (1996), and Bachelor of pharmacy (1987) from Addis Ababa University, Ethiopia.

Academic honours, awards and prizes
Since 2022 - Appointed member of WHO- TDR Global external review group

Since 2021 - Member of WHO-TDR Scientific expert working group for Implementation Research

Winner of the 2020 Donald Mackay Medal for outstanding work in tropical health and awarded annually by the Royal Society of Tropical Medicine and Hygiene (RSTMH) and the American Society of Tropical Medicine & Hygiene.

2016 - 2022 Member of the committee for development research at the Swedish research council

2014 - 2018 Member of the Strategic Advisory Committee for European and Developing Countries Clinical Trial Partnership (EDCTP)

2015- Fellow of the Royal College of Physicians of Edinburgh: FRCP (Edin) http://www.rcpe.ac.uk/membership/fellowship

2015 - Fellow of the African Academy of sciences.

2013 - Honorary Professor of Clinical Pharmacology at the Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia.

Project 1: Pharmacovigilance infrastructure and post-marketing surveillance system capacity building for regional medicine regulatory harmonization in East Africa- (Acronym - PROFORMA) (http://proforma.ki.se/).

PROFORMA is a 5-year project ( (2018 - 2022) funded by the European Union’s Framework Programme for Research and Innovation Horizon 2020 via the European and Developing Countries Clinical Trials Partnership (EDCTP2), with co-funding from Sida

In sub-Saharan Africa, access to medicine, including new drugs, vaccines, and microbicides for treating poverty-related diseases (PRD) is increasing. However, the capacities of the National Medicine Regulatory Authorities (NMRAs) to monitor the quality and public safety of new drugs and interventions are not coping, partly due to a shortage of qualified personnel and limited resources. PROFORMA aims to strengthen the national pharmacovigilance infrastructure and post-marketing surveillance system in Ethiopia, Kenya, Tanzania, and Rwanda by forging partnerships with local academic institutions (training-of-the-trainers for sustainable training programs), national medicine regulatory authorities (practical training to change policy into practice) and public health programs. We aim to generate a cohort of pharmacovigilance-trained human resources from all stockholders, including patients, healthcare providers, and regulatory staff engaged in pharmacovigilance data collection, analysis, interpretation, and data sharing. Our specific objective is to strengthen pharmacovigilance and post-marketing surveillance system focusing on public health programs involving mass drug administration for neglected tropical diseases and mass immunization programs. Twelve postgraduates will be trained to serve as part of the future PV expert regional task force in East Africa aligned with the large-scale African medicine regulatory harmonization and WHO’s Pharmacovigilance program.

Project 2: Safety and efficacy of Dolutegravir and EFV400 for pregnant and breastfeeding women: a randomized non-inferiority clinical trial (Acronym - PREGART) (https://www.pregart.eu/)

PREGART is a 5-year project (2019 - 2023) funded by the European Union’s Framework Programme for Research and Innovation Horizon 2020 via the European and Developing Countries Clinical Trials Partnership (EDCTP2).

Elimination of mother-to-child transmission of HIV is considered one of the priorities for the World Health Organization (WHO) and national programs. Safe and effective antiretroviral drugs during pregnancy and breastfeeding are crucial to achieving the elimination strategy. Dolutegravir (DTG), a second-generation integrase strand transfer inhibitor-based antiretroviral therapy(ART) regimen, demonstrated minimum drug interaction, lower risk of treatment discontinuation, and superior virological suppression against other first-line agents, including efavirenz and boosted protease inhibitors. DTG and low-dose EFV 400mg/day (EFV400) is recommended by WHO as an alternative first-line regimen for adults. Safety and efficacy data on using DTG and EFV400 in pregnant and breastfeeding women are unavailable. Both DTG and EFV are metabolized by genetically polymorphic enzymes UGT1A1 and CYP2B6, respectively. Investigating the pharmacokinetics (PK), pharmacodynamics (PD), and pharmacogenetics (PGx) of DTG in resource-limited genetically diverse African populations is an important step toward optimizing antiretroviral therapy during pregnancy and breastfeeding. We propose a multi-national, three-arm clinical trial to identify the optimal ART regimen for pregnant and breastfeeding women by comparing three alternative ART regimens. The specific objectives are: 1) To show that [TDF, 3TC, DTG] is non-inferior to [TDF, 3TC, EFV600]; 2) To show that [TDF, 3TC, EFV400] is non-inferior to [TDF, 3TC, EFV600]; 3) To compare safety and efficacy of [TDF, 3TC, DTG] with [TDF, 3TC, EFV400]. Using population PK/PD/PGx modeling and simulation as a sub-study, we will identify optimal doses of DTG for pregnant and breastfeeding women. We plan to enroll 1830 HIV-infected pregnant mothers in Ethiopia and Uganda in a three-arm randomized non-inferiority trial with an equal allocation ratio. A subset of the subjects will also undergo a PK/PD/PGx study to determine the optimized doses for pregnant and breastfeeding women.

Expected outcomes: PREGART will generate scientific evidence-based recommendations on the safety and efficacy of EFV400 and DTG during pregnancy and breastfeeding and to be used as a first-line ART regimen for HIV-infected pregnant and breastfeeding women. PK/PD/PGx data will also be generated to further support the dosing of EFV and DTG during pregnancy and breastfeeding.

Project 3: Effectiveness dihydroartemisinin -piperaquine versus sulfadoxine-pyrimethamine for prevention of falciparum malaria infection during pregnancy in Tanzania.

This a 5-year project funded by a grant from Sida.

Intermittent Preventive Treatment in pregnancy (IPTp) with Sulfadoxine/Pyrimethamine (SP) is the current chemoprophylaxis intervention recommended by the WHO for malaria prevention in pregnancy. However, the high prevalence of Sulfadoxine/Pyrimethamine (SP) resistance in high malaria-endemic areas, including Tanzania, is likely to undermine the use of IPTp-SP in improving birth outcomes. We investigate whether the combination of dihydroartemisinin-piperaquine (DHP) is superior to SP alone for preventing malaria in pregnancy among HIV-negative. The study design is an open-label, two-arm, prospective, randomized controlled trial. HIV-negative pregnant women are randomized to receive either IPTp-SP or IPTp-DHP. The result of this study will establish if DHP can be a suitable alternative to replace SP for IPTp for malaria prevention in HIV-negative pregnant women.

Project 4: Randomized clinical trial to determine the efficacy and safety of Praziquantel combined with Dihydroartemisinin-Piperaquine versus Praziquantel alone for treating schistosomiasis in Tanzania.

This a 5-year project funded by a grant from Sida.

Neglected tropical diseases (NTDs) such as schistosomiasis remain a burden in Sub-Saharan Africa (SSA), creating a public health concern. NTDs are linked to almost all Sustainable development goals (SDGs), and their control directly impacts achieving the MDGs, such as reducing poverty and education. The prevalence of schistosomiasis remains high in SSA, affecting more than 200 million people worldwide, of which more than 80% are found in the SSA. Despite the use of praziquantel (PZQ) for mass treatment and disease control, the prevalence of schistosomiasis remains high in some endemic settings. PZQ is effective against mature Schistosoma species but has low efficacy against immature schistosomes (juvenile schistosomes). Previous studies report that artemisinin and its derivatives are effective against immature schistosomes. In a randomized clinical trial, we investigate the efficacy and safety of praziquantel combined with Dihydroartemisinin-Piperaquine versus Praziquantel alone for treating schistosomiasis. We hypothesize that PZQ plus dihydroartemisinin-piperaquine (DHP) will improve schistosomiasis treatment outcomes by covering both matured and immature parasite forms and eventually control the disease is achieved.

Supervision to doctoral degree

• Adam Mitangu Fimbo, Pharmacovigilance of mass drug administration as preventive chemotherapy to control and eliminate lymphatic filariasis in Tanzania, https://openarchive.ki.se/articles/thesis/Pharmacovigilance_of_mass_drug_administration_as_preventive_chemotherapy_to_control_and_eliminate_lymphatic_filariasis_in_Tanzania/26911588?file=48955090
• Joseph Kabatende, Pharmacovigilance of mass drug administration for the control of schistosomiasis and soil transmitted helminths in Rwanda., https://openarchive.ki.se/xmlui/handle/10616/48601, 2023