Human immunodeficiency virus type 1 pharmacogenomics in clinical practice: relevance of HIV-1 drug resistance testing (Part 1).
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 healthcare 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 ofgenomics 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.
Patarca
Roberto
R
E.M. Papper Laboratory of Clinical Immunology and Molecular Biology, University of Miami School of Medicine, Miami, Florida 33101, USA. rpatarca@pol.net
Isava
Alejandro
A
Campo
Rafael
R
Rodriguez
Nelson J
NJ
Nunez
Enriqueta
E
Alter
Michael
M
Marchette
Margaret
M
Sanabia
Mirtha M
MM
Mitchell
Charles
C
Rivera
Delia
D
Scott
Gwendolyn
G
Jayaweera
Dushyantha
D
Moreno
Jose
J
Boulanger
Catherine
C
Kolber
Michael
M
Mask
Cindy W
CW
Sierra
Eduardo Meneses
EM
Vallejo
Ricardo
R
Page
J Brian
JB
Klimas
Nancy G
NG
Fletcher
Mary Ann
MA
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017277:Drug Approval; D024882:Drug Resistance, Viral / Q000235:genetics*; D015658:HIV Infections / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D009154:Mutation; D014481:United States; D014486:United States Food and Drug Administration
D019380:Anti-HIV Agents