Human genetic variability and HIV treatment response.
Access to potent antiretroviral medications greatly reduces morbidity and mortality due to HIV/AIDS, but drug toxicity limits treatment success in many individuals. The field of pharmacogenomics strives to understand the influence of human genetic variants in response to medications. Investigators have begun to identify associations among human genetic variants, predisposition to HIV drug toxicities, and likelihood of virologic response. These include associations among abacavir hypersensitivity reactions, HLA type, and hsp70-hom genotypes, and among CYP2B6 polymorphisms, efavirenz pharmacokinetics, and central nervous system symptoms. Pharmacogenomics also holds great promise to suggest novel targets for drug development. The discovery that a naturally occurring, nonfunctional variant of the HIV receptor gene CCR5 protected against HIV infection encouraged the development of CCR5 antagonists. Through continued translational and applied research, pharmacogenomics will ultimately benefit persons living with HIV worldwide by identifying new therapeutic targets and through individualized drug prescribing that is informed by human genetic testing.
Haas
David W
DW
Vanderbilt AIDS Clinical Trials Center, 345 24th Avenue North, Suite 105, Nashville, TN 37203, USA. david.w.haas@vanderbilt.edu
D000480:Alkynes; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D010078:Oxazines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D010597:Pharmacogenetics; D011506:Proteins / Q000235:genetics*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome; D000099227:Abacavir
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D015224:Dideoxynucleosides; D010078:Oxazines; D011506:Proteins; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C098320:efavirenz