CAROLINE SIMIYU posteradmin
POLYMORPHISMS OF THE HUMAN DRUG METABOLISM GENE CYP2B6 AMONG HIV INFECTED CHILDREN IN NAIROBI, KENYA
Caroline Simiyu1,2, Elijah Songok2, Raphael Lihana2, Fred Wamunyokoli1
Jomo Kenyatta University of Agriculture and Technology1
Kenya Medical Research Institute2
This study aims to determine polymorphisms in the human drug metabolism gene CYP2B6 among HIV infected children in Nairobi, Kenya.
Advent of antiretroviral therapy (ART) as a standard of care has significantly reduced morbidity and mortality due to HIV/AIDS globally. However, individual differences in tolerance and toxicity to ART have been observed in multiple populations resulting in poor adherence and development of drug resistance. Genetic polymorphism in antiretroviral drug metabolism enzyme and transporter genes has been indicated to significantly contribute to ART outcome. Non-nucleoside reverse transcriptase inhibitors efavirenz and nevirapine which are widely used in sub Saharan Africa countries have been shown to have a high inter-individual variability in their pharmacokinetics. Low plasma levels are associated with treatment failure while high plasma levels result in toxicities. CYP2B6 plays a role in metabolism of efavirenz and nevirapine. Polymorphisms of CYP2B6 affect therapeutic outcome of efavirenz and nevirapine. These gene variants are common among people of African ancestry thus understanding the status of CYP2B6 polymorphisms in the African population is critical to ensure an effective therapy outcome.
The study will be conducted on 200 HIV infected children in the Lea Toto cohort. DNA will be obtained from blood samples after which amplification by PCR will be conducted for the CYP2B6 gene. The resulting amplicon will be sequenced using illumina MiSeq and, thereafter, analysis using bioinformatics tools.
Results/ Expected outcome:
This proposed study will provide data on the status of CYP2B6 polymorphisms among HIV infected children in Kenya and the association with ART treatment failure. This will inform on decisions to include screening for CYP2B6 polymorphisms as part of the national HIV treatment policy.
Understanding the status of CYP2B6 polymorphisms in the African population is critical to ensure an effective antiretroviral therapy outcome.