Although the ever-expanding armamentarium of antiretroviral drugs has significantly decreased the morbidity and mortality due to human immunodeficiency virus infection, patients and clinicians are increasingly faced with the problems of inadequate or toxic response to therapy that may be genetically mediated. Significant evidence now exists that interindividual differences, such as efficacy of therapy, hypersensitivity reactions, and metabolic complications as a result of antiretroviral therapy, are in part genetically determined. This article reviews the significant studies published to date in the area of the pharmacogenetics of antiretroviral therapy and summarizes current trends, as well as areas where further research is needed.
Antiretroviral therapy for HIV infection has been available since the introduction and approval of zidovudine in 1986. At the time of writing, nearly 20 drugs in 4 classes and a number of immunomodulatory and other adjunctive agents are available for the treatment of HIV infection in the United States. The use of combinations of antiretroviral drugs to provide potent antiretroviral therapy (ART) has dramatically impacted the morbidity and mortality due to HIV infection and AIDS. However, clinicians are increasingly faced with challenges in the selection and management of ART regimens, including the choice of most efficacious therapy, the avoidance of drug toxicity, and the impact of drug-drug interactions. Although the introduction of viral genotyping and combination-therapy pharmacokinetic data has provided some guidance, the investigation of host genetic factors that impact both the efficacy and toxicity of ART may also aid in selecting the best regimen for individual patients.