Pharmacogenomics of HIV.
The antiretroviral treatment of HIV infection has expanded tremendously in the last few years. This trend is mainly a result of new assays, genetic advances and recombinant DNA technologies providing new insights into HIV virology, pathology and resistance mechanisms. Since 1995, the use of highly active antiretroviral therapy (HAART) as a combination of substances directed against various steps in the viral life cycle, has led to significant decreases in the morbidity and mortality associated with HIV infections. The ability to quantify viral load and to perform sequence analyses represent valuable tools both for understanding the pathogenic actions of the virus and for clinical drug monitoring of HIV-infected patients. Laboratory tests have been developed and validated to help predict which antiviral substances may be more effective to control viral replication in a given patient. Genotypic and phenotypic assays have been developed to assess HIV antiviral resistance. The ability to predict drug response from a certain genotypic or phenotypic setting with respect to drug absorption, drug metabolism and drug elimination is continually evolving. This may lead to significant changes in drug plasma concentrations and may affect the efficacy and toxicity of antivirals. More recently, drug/drug interactions and mutation/drug correlations have been discovered. However, the optimal usage of pharmacogenetic and pharmacogenomic tools in the clinic still remains to be defined. This review summarizes mechanisms of drug bioavailability with respect to pharmacogenomics and discusses the impact and clinical benefit of 'personalized' HIV therapy.
Ast
Oliver
O
Berlex Biosciences, 2600 Hilltop Drive, PO Box 4099, CA 94804-0099, USA. Oliver_Ast@berlex.com
Lüke
Wolfgang
W
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D023241:Antiretroviral Therapy, Highly Active / Q000639:trends; D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D006678:HIV / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D010597:Pharmacogenetics; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
D000998:Antiviral Agents