The clinical implications of antiretroviral pharmacogenomics.
Heterogeneity exists in the effectiveness and toxic effects of antiretroviral agents between individuals and populations. Although patient-related clinical variables such as age, sex and ethnic origin have been associated with drug response, inherited predispositions may have a significant effect on treatment outcome. The role of host and pathogen pharmacogenomics is gaining increasing interest in the field of both antiretrovirals in development, such as the chemokine (C-C motif) receptor 5 (CCR5) inhibitors, and in established therapies where toxicity and efficacy may be predicted. Despite numerous studies available in the literature, the interpretation of the relationship between genetic polymorphisms and clinical outcomes is often posed with many confounding variables, making clinical interpretations of these results difficult. This review summarizes the key findings in the growing knowledge between human genetics and response to antiretroviral drugs and how these findings may be effectively applied in a clinical context.
Fox
Julie
J
St. Mary's Hospital, Clinical Trials Centre, Winston Churchill Wing, Division of Medicine, Imperial College London, Praed Street, London W2 1NY, UK.
Boffito
Marta
M
Winston
Alan
A
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000145:classification / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D065100:CCR5 Receptor Antagonists; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000494:pharmacology; D004342:Drug Hypersensitivity / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D015497:HIV-1; D039682:HIV-Associated Lipodystrophy Syndrome / Q000209:etiology; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D000099227:Abacavir
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir