Pharmacogenetic & Pharmacokinetic Biomarker for Efavirenz Based ARV and Rifampicin Based Anti-TB Drug Induced Liver Injury in TB-HIV Infected Patients

BACKGROUND: Implication of pharmacogenetic variations and efavirenz pharmacokinetics in concomitant efavirenz based antiviral therapy and anti-tubercular drug induced liver injury (DILI) has not been yet studied. We performed a prospective case-control association study to identify the incidence, pharmacogenetic, pharmacokinetic and biochemical predictors for anti-tubercular and antiretroviral drugs induced liver injury (DILI) in HIV and tuberculosis (TB) co-infected patients. METHODS AND FINDINGS: Newly diagnosed treatment naïve TB-HIV co-infected patients (n = 353) were enrolled to receive efavirenz based ART and rifampicin based anti-TB therapy, and assessed clinically and biochemically for DILI up to 56 weeks. Quantification of plasma efavirenz and 8-hydroxyefaviernz levels and genotyping for NAT2, CYP2B6, CYP3A5, ABCB1, UGT2B7 and SLCO1B1 genes were done. The incidence of DILI and identification of predictors was evaluated using survival analysis and the Cox Proportional Hazards Model. The incidence of DILI was 30.0%, or 14.5 per 1000 person-week, and that of severe was 18.4%, or 7.49 per 1000 person-week. A statistically significant association of DILI with being of the female sex (p = 0.001), higher plasma efavirenz level (p = 0.009), efavirenz/8-hydroxyefavirenz ratio (p = 0.036), baseline AST (p = 0.022), ALT (p = 0.014), lower hemoglobin (p = 0.008), and serum albumin (p = 0.007), NAT2 slow-acetylator genotype (p = 0.039) and ABCB1 3435TT genotype (p = 0.001). CONCLUSION: We report high incidence of anti-tubercular and antiretroviral DILI in Ethiopian patients. Between patient variability in systemic efavirenz exposure and pharmacogenetic variations in NAT2, CYP2B6 and ABCB1 genes determines susceptibility to DILI in TB-HIV co-infected patients. Close monitoring of plasma efavirenz level and liver enzymes during early therapy and/or genotyping practice in HIV clinics is recommended for early identification of patients at risk of DILI

Output from the CIHR Canadian HIV Trials Network international postdoctoral fellowship for capacity building in HIV clinical trials

CITATION: Mbuagbaw, L., et al. 2018. Output from the CIHR Canadian HIV Trials Network international postdoctoral fellowship for capacity building in HIV clinical trials. HIV/AIDS - Research and Palliative Care, 10:151-155, doi:10.2147/HIV.S150107.The original publication is available at https://www.dovepress.comENGLISH ABSTRACT: As a response to the human immunodeficiency virus (HIV) epidemic and part of Canadian Institutes for Health Research’s mandate to support international health research capacity building, the Canadian Institutes for Health Research Canadian HIV Trial Network (CTN) developed an international postdoctoral fellowship award under the CTN’s Postdoctoral Fellowship Awards Program to support and train young HIV researchers in resource-limited settings. Since 2010, the fellowship has been awarded to eight fellows in Cameroon, China, Lesotho, South Africa, Uganda and Zambia. These fellows have conducted research on a wide variety of topics and have built a strong network of collaboration and scientific productivity, with 40 peer-reviewed publications produced by six fellows during their fellowships. They delivered two workshops at international conferences and have continued to secure funding for their research, using the fellowship as a stepping stone. The CTN has been successful in building local HIV research capacity and forming a strong network of like-minded junior low- and middle-income country researchers with high levels of research productivity. They have developed into mentors, supervisors and faculty members, who, in turn, build local capacity. The sustainability of this international fellowship award relies on the recognition of its strengths and the involvement of other stakeholders for additional resources.https://www.dovepress.com/output-from-the-cihr-canadian-hiv-trials-network-international-postdoc-peer-reviewed-article-HIV#Publisher's versio

Output from the CIHR Canadian HIV Trials Network international postdoctoral fellowship for capacity building in HIV clinical trials

Lawrence Mbuagbaw,1–3 Amy L Slogrove,4,5 Jacqueline Sas,6 John Lengwe Kunda,7 Frederick Morfaw,8 Jackson K Mukonzo,9 Wei Cao,10–12 Gisele Ngomba-Kadima,13 Moleen Zunza,14,15 Pierre Ongolo-Zogo,3 Philip N Nana,8 Anne Cockcroft,16,17 Neil Andersson,16,18,19 Nelson Sewankambo,9 Mark F Cotton,4 Taisheng Li,12 Taryn Young,14 Joel Singer,5,6 Jean-Pierre Routy,6,10,11,20 Colin JD Ross,21 Kyaw Thin,22 Lehana Thabane,1,2,6,23–25 Aslam H Anis5,6 1Department of Health Research Methods, Evidence and Impact, McMaster University, 2Biostatistics Unit, Father Sean O’Sullivan Research Centre, St Joseph’s Healthcare Hamilton, Hamilton, ON, Canada; 3Centre for Development of Best Practices in Health, Yaoundé Central Hospital, Yaoundé, Cameroon; 4Department of Paediatrics and Child Health, Family Clinical Research Unit (FAM-CRU), Stellenbosch University, Tygerberg, South Africa; 5UBC School of Population and Public Health, Vancouver, BC, 6CIHR Canadian HIV Trials Network, UBC, Canada; 7Community Information and Epidemiological Technologies (CIET), Lusaka, Zambia; 8Department of Obstetrics and Gynaecology, Faculty of Medicines and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon; 9School of Biomedical Sciences, College of Health Sciences, University of Makerere, Kampala, Uganda; 10Chronic Viral Illness Service, McGill University Health Centre, 11Research Institute of the McGill University Health Centre, Montreal, QC, Canada; 12Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; 13Queen Mamahato Memorial Hospital, Maseru, Lesotho; 14Centre for Evidence-based Health Care, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa; 15Research Institute, McGill University Health Centre, Montreal, QC, Canada; 16Community Information and Epidemiological Technologies (CIET) Trust Botswana, Gaborone, Botswana; 17Community Information and Epidemiological Technologies – Participatory Research at McGill (CIET-PRAM), Department of Family Medicine, McGill University, 18Centro de Investigación de Enfermedades Tropicales, Universidad Autónoma de Guerrero, Chilpancingo, Mexico; 19Department of Family Medicine, McGill University, Montreal, Canada; 20Division of Hematology, McGill University Health Centre, Montreal, QC, Canada; 21Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 22Research Coordination Unit, Ministry of Health and Social Welfare, Maseru, Lesotho; 23Departments of Paediatrics and Anaesthesia, McMaster University, Hamilton, ON, Canada; 24Centre for Evaluation of Medicine, St Joseph’s Healthcare—Hamilton, ON, Canada; 25Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada Abstract: As a response to the human immunodeficiency virus (HIV) epidemic and part of ­Canadian Institutes for Health Research’s mandate to support international health research capacity building, the Canadian Institutes for Health Research Canadian HIV Trial Network (CTN) developed an international postdoctoral fellowship award under the CTN’s Postdoctoral Fellowship Awards Program to support and train young HIV researchers in resource-limited settings. Since 2010, the fellowship has been awarded to eight fellows in Cameroon, China, Lesotho, South Africa, Uganda and Zambia. These fellows have conducted research on a wide variety of topics and have built a strong network of collaboration and scientific productivity, with 40 peer-reviewed publications produced by six fellows during their fellowships. They delivered two workshops at international conferences and have continued to secure funding for their research, using the fellowship as a stepping stone. The CTN has been successful in building local HIV research capacity and forming a strong network of like-minded junior low- and middle-income country researchers with high levels of research productivity. They have developed into mentors, supervisors and faculty members, who, in turn, build local capacity. The sustainability of this international fellowship award relies on the recognition of its strengths and the involvement of other stakeholders for additional resources. Keywords: CTN, postdoctoral fellowship, capacity building, clinical trials, networkin