Abstract
Sub Saharan Africans represent the most genetically diverse population in the world, characterized by extensive population substructure and less linkage disequilibrium between loci. Pharmacogenetic research in Africa is progressing through regional and international research collaborations. The African pharmacogenomics consortium is established to prompt research and deliver guidelines for the use of pharmacogenomics-based tests in African populations.
Africa is affected by a high prevalence of HIV/AIDS, tuberculosis, and malaria. Co-infection of these diseases is common, but co-treatment is challenging due to drug interactions and overlapping toxicities. Pharmacogenetic studies focusing on the treatment optimization of HIV/AIDS, and its comorbidities are conducted in different African populations. However, between-country extrapolation of data is not feasible due to vast population genetic diversity. CYP2B6 metabolizes antiretrovirals such as efavirenz and nevirapine as well as antimalarial drugs. Defective CYP2B6 variant alleles occur at a higher frequency in black-African ancestries. The frequency of CYP2B6*6 allele, which is associated with high efavirenz plasma exposure, drug induced liver and neuropsychiatric toxicities, reach up to 40%. Genome-wide association studies revealed potential novel genetic biomarkers for antiretroviral and anti-tuberculosis drugs induced liver toxicities. HLA-B*57 alleles (B*57:03 and B*57:02) confer susceptibility to antituberculosis and antiretroviral drugs induced liver toxicity. HLA-C*04:01 allele is associated with nevirapine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in sub-Saharan Africans.
The importance of pharmacogenetic variations in modulating interactions between antiretroviral, antituberculosis, antimalarial drugs is noted. Reduced efavirenz metabolism in black Africans, partly due to CYP2B6 genotype counterbalancing the effect of CYP enzyme induction by rifampicin, necessitated different efavirenz dosing strategy during rifampicin-efvairenz co-treatment. CYP2B6 genotype based efavirenz dose modification for sub-Saharan Africa population is recently recommended. Bed-side pharmacogenetics test for genotype-based drug dosing, its clinical use and applicability remain to be investigated to translate pharmacogenetic research into clinical practice in Africa. In this presentation, key pharmacogenetic studies in different African populations, with focus on treatment optimization of HIV/AIDS and its comorbidities such as tuberculosis and malaria will be presented. Effect of pharmacogenetic variations on first-line antiretroviral, antituberculosis and antimalarial drug interactions, and its impact on treatment outcomes will be summarized.
