Analysis of HIV-1 mutation patterns in patients failing antiretroviral therapy.
The emergence of mutations encoding drug resistance is supposed to be a significant limitation to the clinical efficacy of inhibitor compounds directed against specific HIV-1 enzymatic targets. We have used a commercial test (Visible Genetics Inc., Paris, France) to study the prevalence of mutations occurred in HIV-1 protease and reverse transcriptase (RT) genes in 93 HIV-1 infected patients treated with at least one regimen containing a protease inhibitor (PI) and failing to the current therapeutic regimen. Protease mutations conferring resistance to at least one PI were detected in 46/93 (49.4%) of strains, 25 (26.8%) of which showed resistance to all PIs. Reverse transcriptase mutations conferring resistance to at least one RT inhibitor were detected in 57/93 (61.2%) of strains, 18 (19.3%) of which showed resistance to all RT inhibitors. The most frequent RT mutations were T215Y/F, M41L, and M184V (41.9, 40.8, and 40.8%, respectively), while L63P, L10R/V, and A71V/T (58, 41.9, and 34.4%, respectively) were the most represented protease substitutions. We have found no mutations encoding for multiple dideoxynucleoside resistance (Q151M or T69SS). Twelve of our patients (12.9%) had no mutation encoding drug resistance and were completely sensitive to all RT and protease inhibitors. Therefore, not all virological failures are caused by HIV-1 genomic resistance.
Quiros-Roldan
E
E
Institute of Infectious and Tropical Diseases, University of Brescia, Italy. carosi@master.cci.unibs.it
Signorini
S
S
Castelli
F
F
Torti
C
C
Patroni
A
A
Airoldi
M
M
Carosi
G
G
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000821:virology*; D000998:Antiviral Agents / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial / Q000235:genetics*; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D009154:Mutation; D019888:Nelfinavir / Q000627:therapeutic use; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D019258:Saquinavir / Q000627:therapeutic use; D017211:Treatment Failure; D015215:Zidovudine / Q000627:therapeutic use
D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D015215:Zidovudine; D012194:RNA-Directed DNA Polymerase; D016333:HIV Protease; D019888:Nelfinavir; D019258:Saquinavir