Pharmacogenetics: a practical role in predicting antiretroviral drug toxicity?
Research into the toxic effects of antiretroviral therapy has made tremendous progress, particularly over the 5 years since the earliest descriptions of the lipodystrophy syndrome. In particular, the contribution of specific antiretroviral drugs to these toxicity syndromes is becoming clearer, along with their pathophysiological mechanisms. This knowledge can now direct research on host genetic factors that may significantly influence the risk of both short-term and long-term toxicities. At present, the genetic association with abacavir hypersensitivity appears sufficiently strong to consider pharmacogenetic testing in clinical practice, although further corroborative research is still needed. The future will see increasing use of both pharmacogenetics (the genetic basis for variation in the response to specific medications) and immunogenetics (the genetic basis for variation in the response to specific antigens). The identification of an increasing number of genetic associations with drug efficacy/toxicity may, or may not, result in widespread genetic testing, but it will certainly increase our understanding of the mechanisms of both desirable and adverse drug effects and inform drug development.
Nolan
David
D
Centre for Clinical Immunology and Biomedical Statistics, 2nd Floor, North Block, Royal Perth Hospital, Wellington Street, Perth 6000, Western Australia.
Gaudieri
Silvana
S
Mallal
Simon
S
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000097:blood / Q000235:genetics; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D015235:HLA-B Antigens / Q000097:blood / Q000235:genetics; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D011237:Predictive Value of Tests; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000099227:Abacavir
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015224:Dideoxynucleosides; D017320:HIV Protease Inhibitors; D015235:HLA-B Antigens; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir; C484830:HLA-B*57:01 antigen