Genomic diversity of African population and pharmacogenetics in the safe and efficacious use of efavirenz in the treatment of HIV/AIDS
3rd World Congress on Pharmacology
August 08-10, 2016 Birmingham, UK

Collen Masimirembwa

African Institute of Biomedical Science and Technology, Zimbabwe

Posters & Accepted Abstracts: Clin Exp Pharmacol

Abstract:

There is limited data on the genomic diversity of African population and its implications for medicine. We therefore, explored the genomic diversity of African population and investigated the pharmacogenetics of efavirenz in the treatment of HIV/AIDS patients. 2000 DNA samples from individuals belonging to 10 major African ethnic groups, the Yoruba, Ibo and Hausa (Nigeria), the Kikuyu, Luo and Masaai from Kenya, the Shona, Ndebele and San (Zimbabwe), and the Venda (South Africa) were genotyped using the illumina 600K SNP microarray chip. The samples were also genotyped using traditional PCR methods for 20 SNPs in 6 pharmacogenes (NAT-2, FMO, CYP2B6, CYP2D6, CYP2C19, and GSTM). The data were analyzed using principal component analysis. The pharmacogenetics of efavirenz, were studied in 500 HIV/AIDS patients on anti-retroviral treatment. The role of CYP2B6 genetic variants as possible biomarkers for CNS has adverse effects associated with the use of efavirenz was explored. A pharmacogenetics guided dosing algorithm was derived using pharmacometric modeling. The population genotyping confirmed, with greater resolution that the genomic diversity of African population is more when compared to Caucasian and Asian populations. The results of the efavirenz pharmacogenetics study showed that the low activity of CYP2B6*6 variant is more prevalent in African populations, which correlated with more patients having high drug concentrations and higher incidences of CNS side effects. The pharmacogenetics guided dosing algorithm showed that patients homozygous for the CYP2B6*6 required 200 mg/day of efavirenz compared to the standard dose of 600 mg/day. More than 20% of patients in Africa would require such dose reduction.

Biography :

Email: collen.masimirembwa@aibst.com