Pharmacogenetics of antiretroviral agents

The past year has seen the first whole genome association study for determinants of host control of HIV, as well as a number of hypothesis-driven candidate gene studies defining determinants of pharmacokinetics and toxicity of antiretroviral drugs. This review summarizes some of these findings, but it must be noted that the field is moving with unprecedented speed.

A number of novel polymorphisms have been reported in the CYP2B6 locus that influence pharmacokinetics of non-nucleoside reverse transcriptase inhibitors. Among these are some novel nonsynonomous single nucleotide polymorphisms such as 983T > C (CYP2B6 18) and 499C > G (CYP2B6 26), as well as a partial deletion (CYP2B6 29). In addition, the concept of dose reduction according to CYP2B6 genotype has now been tested with some promising but preliminary results. Some other important advances in our knowledge have also been made, such as the association of TA repeats in the UGT1A1 regulatory region (UGT1A1 28) with atazanavir-related hyperbilirubinaemia and the association of ABCC2 and ABCC4 single nucleotide polymorphisms with tenofovir-associated renal toxicity.

Treatment response to antiretrovirals is governed by genetic and environmental factors as well as adherence to therapy. Variability exists within pharmacological, immune and viral genes, and future studies must co-ordinate these issues.