Pharmacogenetics of Antiretroviral Drug Response and Pharmacokinetic Variations in Indigenous South African Populations

Interindividual and interethnic differences in response to antiretroviral drugs (ARVs) are influenced by genetic variation. The few genomic studies conducted among African-Americans and African ethnic groups do not reflect the extensive genetic diversity within African populations. ARVs are widely used in Africa. Therefore, genomic characterization of African populations is required before genotype-guided dosing becomes possible. The aim of this study was to determine and report on the frequency of genetic variants in genes implicated in metabolism and transport of ARVs in South African populations. The study comprised 48 self-reported South African Colored (SAC) and 296 self-reported Black African (BA) individuals. Allele and genotype frequency distributions for 93 variants contributing to metabolism and transport of ARVs were compared between groups, and other global populations. Fifty-three variants had significant differences in allele and genotype frequencies when comparing SAC and BA groups. Thirteen of these have strong clinical annotations, affecting efavirenz and tenofovir pharmacokinetics. This study provides a summary of the genetic variation within genes implicated in metabolism and transport of ARVs in indigenous South African populations. The observed differences between indigenous population groups, and between these groups and global populations, demonstrate that data generated from specific African populations cannot be used to infer genetic diversity within other populations on the continent. These results highlight the need for comprehensive characterization of genetic variation within indigenous African populations, and the clinical utility of these variants in ARV dosing for global precision medicine. Population pharmacogenetics is a nascent field of global health and warrants further research and education.