HIV Pharmacogenetics and Pharmacogenomics

Thirty years after the identification of the human immunodeficiency virus (HIV) as the etiologic agent for AIDS, there are still no effective vaccines and no sterilizing cures. Fortunately, combination antiretroviral therapy (cART) has turned a deadly disease into a manageable, chronic condition. Effective and lifelong antiretroviral therapy is the foundation of the fight to reduce HIV-associated morbidity and mortality, and to improve the quality of life for the estimated 33.3 million persons living with HIV. Antiretroviral treatment, however, is associated with a number of toxicities that range from mild to life-threatening and that affect nearly all organ systems. As the number of people on cART increases and the population ages, genetic predictors of toxicities and age-related morbidities due to cART become increasingly critical. There has been intensive genetic investigation in an effort to explain the variability in HIV/AIDS, to identify potential targets for therapeutic intervention, and to reveal the genetic basis for interpersonal and interpopulation variation in efficacy and toxicities associated with antiretroviral therapies [An, P. and Winkler, C.A. (2010) Trends Genet 26, 119–131; Aouizerat, B.E., Pearce, C.L. and Miaskowski, C. (2011) Curr HIV/AIDS Rep 8, 38–44; Tozzi, V. (2010) Antiviral Res 85, 190–200]. These studies have identified a number of genetic variants that are important correlates of HIV pathogenesis and antiretroviral therapy. Whole-genome association studies in the general population have revealed genetic factors associated with metabolic disorders (i.e., type 2 diabetes mellitus and lipodystrophy); genetic profiling might have utility in the choice of cART regimens to avoid drugs associated with metabolic toxicities. Pharmacogenetics is just beginning to be incorporated into clinical practice, most notably screening for HLA-B*5701 , which is associated with abacavir hypersensitivity reaction. Here we review the role of pharmacogenetics and pharmacogenomics in HIV therapy and drug-related toxicities, the utility of genetic screening for personalized HIV care, and what is needed to bring personalized, genetics-informed care to the clinic.