Human immunodeficiency virus type 1 pharmacogenomics in clinical practice: Relevance of HIV-1 drug resistance testing (part 1)

Roberto Patarca, Alejandro Isava, Rafael Campo, Nelson J. Rodriguez, Enriqueta Nunez, Michael Alter, Margaret Marchette, Mirtha M. Sanabia, Charles Mitchell, Delia Rivera, Gwendolyn Scott, Dushyantha Jayaweera, Jose Moreno, Catherine Boulanger, Michael Kolber, Cindy W. Mask, Eduardo Meneses Sierra, Ricardo Vallejo, J. Brian Page, Nancy G. KlimasMary Ann Fletcher

Research output: Contribution to journalReview articlepeer-review

4 Scopus citations

Abstract

Throughout most of the past century, physicians could offer patients no treatments for infections caused by viruses. The experience with treatment of infection by human immunodeficiency virus (HIV) has changed the way health-care workers deal with viral infections and has triggered a growing rate of discovery and use of antiviral agents, the first fruits of the expanding genomics revolution. HIV treatment also provides an informative paradigm for pharmacogenomics because control of infection and its consequences is limited by the development of viral drug resistance and by host factors. This report summarizes studies published to date on the significance of testing of HIV-1 resistance to antiretroviral drugs. The only Food and Drug Administration-approved kit for HIV drug resistance testing by genotypic sequencing is commercially available through Visible Genetics, Inc. Genotyping sequencing alone is most likely an adequate test to assist in the therapeutic decision-making process for previous regimen failure, for treatment-naïve patients in areas of high prevalence of transmitted resistant virus, and for pregnant women. However, in exceptional cases of highly complex mutation patterns and extensive cross-resistance, it may be useful to obtain a phenotype test, because that result may more easily identify drugs to which virus is least resistant. There are no published clinical trials results on the usefulness of the so-called virtual phenotype over genotypic sequencing alone. Not only has the paradigm of viral pharmacogenomics in the form of HIV genotypic sequencing been useful in treating other viral diseases, but it is also important to the real-life implementation of the growing discipline of genomics or molecular medicine. The application of this paradigm to the thousands of potential therapeutic targets that have become available through the various human genome projects will certainly gradually change the landscape of diagnosis and management of many diseases, including cancer.

Original languageEnglish (US)
Pages (from-to)201-234
Number of pages34
JournalJournal of Environmental Pathology, Toxicology and Oncology
Volume22
Issue number3
DOIs
StatePublished - 2003

Keywords

  • Antiretroviral treatment
  • Drug resistance testing
  • HIV-1
  • Mutations
  • Protease
  • Reverse transcriptase
  • Viral fitness
  • Virus infection

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

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