Pharmacogenetics and the potential for the individualization of antiretroviral therapy.
OBJECTIVE
Genetic associations highlighting differences in the response to HIV infection and treatment have significantly furthered our understanding of the pathogenesis, pharmacokinetics and pharmacodynamics of antiretroviral drug action and toxicities and HIV disease itself. This review focuses on the current knowledge of associations between polymorphisms and treatment outcomes in HIV with particular emphasis on clinically relevant relationships likely to lead to the individualization of antiretroviral therapy.


RESULTS
Our understanding of the immunogenetic basis of drug toxicity has been furthered by human leucocyte antigen associations with hypersensitivities for the antiretroviral drugs abacavir and nevirapine. For abacavir in particular, the use of HLA-B*5701 as a screening test appears to be generalizable across racially diverse populations and has been supported by both observational, and blinded randomized controlled trials.


CONCLUSIONS
Differences in HIV acquisition and progression as well as antiretroviral efficacy and toxicity will continue to provide the basis for research to define the genetic basis of such diversity. Despite the plethora of research in this area, numerous barriers exist to the successful operationalization of genetic testing to the clinic. HLA-B*5701 screening to prevent abacavir hypersensitivity is currently the most relevant to clinical practice and highlights that the promise of cost-effective testing can be facilitated by robust laboratory methodology and quality assurance programs that can be applied to diverse treatment settings.
Phillips
Elizabeth J
EJ
Centre for Clinical Pharmacology & Infectious Diseases, Royal Perth Hospital, Murdoch University, Perth, Australia. e.phillips@murdoch.edu.au
Mallal
Simon A
SA
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004342:Drug Hypersensitivity / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D016896:Treatment Outcome
D019380:Anti-HIV Agents