The role of pharmacogenetics in Efficacy and safety of protease inhibitor based therapy in human immunodeficiency virus type (HIV) infection.

Abstract

Antiretroviral therapy has markedly reduced morbidity and mortality for persons living with human immunodeficiency virus (HIV). HIV can now be classified as a chronic disease; until a cure is found, patients are likely to require life-long therapy. However, despite these undoubted advances, there are many issues that need to be resolved, including the problems associated with long-term efficacy and toxicity. Moreover, pharmacotherapy of patients infected with HIV is challenging because a great number of comorbidities increase polypharmacy and the risk for drug-drug interactions. There is considerable interindividual variability in patient outcomes in terms of drug disposition, drug efficacy and adverse events. The basis of these differences is multifactorial, but host genetics are believed to play a significant part. HIV-infected population consists of ethnically diverse individuals on complex and potentially toxic antiretroviral regimens on a long-term basis. These individuals would benefit greatly from predictive tests that identify the most durable regimens. Pharmacogenetics holds that promise. Thus, detailed understanding of the metabolism and transport of antiretrovirals and the influence of genetics on these pathways is important. To this end, this review provides an up-to-date overview of the metabolism of antiHIV therapeutics of the protease inhibitors Lopinavir and Ritonavir and the impact of genetic variation in drug metabolism and transport on the treatment of HIV.