Pharmacogenetic considerations in the management of HIV infection

Kristina E. Estes, Kristin H. Busse, Scott R. Penzak

Research output: Contribution to journalReview article

Abstract

Potent combination antiretroviral drug therapy has now been available to HIV-infected patients for more than a decade, resulting in a significant decline in disease-related morbidity and mortality. Nonetheless, a number of HIV-infected individuals fail to experience the full benefit of their antiretroviral medications; some lack a robust virologic response, while others experience treatment-limiting toxicities. A number of factors may contribute to variable drug response in patients with HIV infection. Virologic, immunologic, pharmacologic, and pharmacokinetic differences between HIV-infected patients have all been noted to contribute to interpatient variability in drug response. Recent data suggest that pharmacogenetic differences among HIV-infected individuals may also be an important variable that contributes to antiretroviral drug response. Pharmacogenetic studies of antiretroviral drug therapy have explored the influence of single nucleotide polymorphisms in genes responsible for key proteins involved in antiretroviral drug metabolism (cytochrome P50 enzymes) and drug transport (P-glycoprotein). In addition, the human leukocyte antigen genotype (HLA-B*57) has been found to predict abacavir-associated hypersensitivity reactions. Antiretroviral pharmacogenetics offers the possibility of optimizing virologic response and minimizing drug toxicity by individualizing anti-HIV pharmacotherapy. The authors review those genetic polymorphisms that have been shown, or are strongly suspected, to influence antiretroviral drug metabolism, transport, and toxicity.

Original languageEnglish
Pages (from-to)234-245
Number of pages12
JournalJournal of Pharmacy Practice
Volume20
Issue number3
DOIs
StatePublished - Jun 2007

Keywords

  • Cytochrome P450
  • HIV
  • P-glycoprotein
  • Pharmacogenetics
  • Pharmacogenomics

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