The pharmacogenetics of antiretroviral therapy

Although the past 20 years have seen many advances in HIV pharmacotherapy, host variability has only been more recently recognized as an important driver of both treatment response and toxicity. This review will focus on the importance of variability in drug metabolizing enzymes and the potential research and clinical applications of these findings in HIV care.

The treatment of HIV is complex and involves chronic treatment with multiple drugs and drug classes. Recent research has been important in uncovering genetic differences in drug metabolizing and drug transporter genes, which underpin dose-dependent toxicity and efficacy, but also in genes defining differences in immune response and human leukocyte antigen genes, which restrict processes that are less dependent on the drug dose.

The advancement of pharmacogenetics will continue to further our knowledge of disease-drug interactions and pathogenesis. Ultimately, the goals of pharmacogenetics and pharmacogenomics in HIV medicine will be the development of the right drugs for the right patient or population. The strong association between HLA-B5701 and abacavir hypersensitivity reaction shows promise for a genetic screening test to be feasibly incorporated into clinical practice. The clinical applicability of many findings demonstrating associations between single nucleotide polymorphisms, particularly in drug metabolism and transporter genes and drug efficacy and toxicity, are currently uncertain.