I am a Professor of Tropical Pharmacology, senior researcher and research group leader at the division of clinical pharmacology, Department of Laboratory Medicine, Karolinska Institutet.
My main area of research is Tropical Pharmacology, which is clinical pharmacology research with focus on major infectious diseases that are classified as public health problems, the largest 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.
Treatment outcome including safety and efficacy of drugs is complicated by co-infections and disease comorbidities 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, and 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 13 completed and 5 ongoing PhD students registered at Karolinska Institutet, and > 150 original research publications in peer-reviewed scientific journals (https://pubmed.ncbi.nlm.nih.gov/?term=aklillu&sort=date).
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.
Since 2016, I am a member of the committee for development research at the Swedish research council and served as vice-chair and member of the scientific advisory board for the European and Developing Countries Clinical Trials Partnership (EDCTP) during 2014 -2018.
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, microbicides for treatment of poverty-related diseases (PRD) is increasing. However, capacities of the National Medicine Regulatory Authorities (NMRAs) to monitor the quality and public safety of new drugs and interventions are not coping with, partly due to a shortage of qualified personnel and limited resources. PRORFORMA 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, regulatory staffs that are engaged in pharmacovigilance data collection, analysis, interpretation, and data sharing. Our specific objective 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 serves 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 key to achieving the elimination strategy in 2020. 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) are recommended by WHO as an alternative first-line regimen for adults. Safety and efficacy data on the use of DTG and EFV400 in pregnant and breastfeeding women are not yet available. Given the recent evidence that the standard dose of EFV600 might be associated with higher toxicity during pregnancy, DTG and low dose EFV 400mg/day (EFV400) are promising alternatives for pregnant and breastfeeding women pending safety and efficacy data. 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 towards 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]. As a sub-study, using population PK/PD/PGx modeling and simulation, we will identify optimal doses of DTG for pregnant and breastfeeding women. We plan to enroll in 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 be followed to undergo 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 Sulfadoxin/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 and co-trimoxazole alone for the prevention of malaria in pregnancy among HIV negative and HIV positive pregnant women respectively. 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. In parallel, HIV positive pregnant women are randomized to receive either co-trimoxazole (CTX) with DHP (IPTp-DHP+CMX) or CTX alone. The result from this study will establish if DHP can be a suitable alternative to replace SP for IPTp for malaria prevention in HIV negative pregnant women, and the addition of DHP to daily cotrimoxazole is significant in preventing malaria among HIV positive pregnant women.
Project 4: Randomized clinical trial to determine the efficacy and safety of Praziquantel combined with Dihydroartemisinin-Piperaquine versus Praziquantel alone for the treatment of 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 Millennium development goals (MDGs), and their control is associated with a direct impact on the achievement of the MDGs such as reduction of poverty and education. The prevalence of schistosomiasis remains high in SSA, affecting more than 200 million people worldwide, of which more than 80% 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 are investigating the efficacy and safety of praziquantel combined with Dihydroartemisinin-Piperaquine versus Praziquantel alone for the treatment of schistosomiasis. Our hypothesis is PZQ plus dihydroartemisinin-piperaquine (DHP) will improve schistosomiasis treatment outcome by covering both matured and immature forms of a parasite and eventually control of the disease achieved.
Project 5: Factors affecting malaria treatment outcome among pregnant women treated with artemether-lumefantrine in Tanzania
This a 5-year project funded by a grant from Sida.
The expression and metabolic profile of serval hepatic drug-metabolizing enzymes are altered by hormonal and physiological changes during pregnancy. Enhanced antimalarial drug metabolism and lower plasma drug exposure may increase the risks of treatment failure, development of resistance and negative birth outcomes. Receiving the same therapy, the pharmacokinetics and treatment outcome of antimalarial drugs may differ between pregnant and non-pregnant women. Knowledge of the pharmacokinetics of antimalarial drugs and its impact on treatment response in pregnant women is still minimal. In addition, the impact of pharmacogenetic variations on malaria treatment outcome in pregnant women remains to be explored. We are conducting a pharmacogenetic and pharmacokinetic prospective cohort study in pregnant women with uncomplicated Plasmodium falciparum infection treated with artemisinin lumefantrine combination therapy in Tanzania.
Project 6: Optimization of pediatric antiretroviral therapy in sub-Saharan Africa.
This a 4-year project funded by a grant from the Swedish research council
Efavirenz (EFV), a potent antiretroviral drug is approved by US-FDA and WHO to treat HIV infected children > 3 years of age. US-FDA has recently expanded the use of efavirenz (EFV) based ART for children aged ≥ 3 months weighing > 3.5 kg. However, waiting for more pharmacokinetic (PK) safety and efficacy data in children, WHO continues to limit the use of EFV in children < 3 years of age. The current body weight-based EFV dose recommendation to treat infants and children is a scaled-down prediction from population PK modeling of data obtained from adults treated with the standard maximum EFV dose (600mg/day). We are conducting a three-phase efavirenz pharmacokinetics, pharmacogenetics and pharmacodynamics based dose optimization study in HIV and HIV-TB co-infected children in Uganda and Ethiopia. The result of this study will provide an evidence-based recommendation for policymakers to develop effective pediatric HIV treatment guidelines, particularly in Sub-Saharan Africa.
Project 7: Pharmacokinetics and Pharmacogenetics of Cyclophosphamide and tamoxifen for the treatment of Breast Cancer patients in Ethiopia.
This study is funded by a grant from Sida.
Breast cancer in women of black African origin is characterized by the younger age of onset, clinically aggressive with a high prevalence of triple-negative tumors, and higher mortality rates than age-matched Caucasian women. Cyclophosphamide and tamoxifen are the cornerstones of breast cancer chemotherapy. Both drugs are metabolized by genetically polymorphic cytochrome P450 enzymes and display a wide between patient variations in their plasma concentrations. In a cross-sectional study design, we investigate the impact of pharmacogenetics on the pharmacokinetics of cyclophosphamide and tamoxifen, as we as the incidence and predictors of chemotherapy-induced hematologic toxicities and reduced relative dose intensity in Ethiopian breast cancer patients.
- 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
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.
Since 2016 - 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
2013 - Honorary Professor of Clinical Pharmacology at Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Serbia.