Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy.
The role of mutations in protease (PR) and reverse-transcriptase (RT) of human immunodeficiency virus (HIV) in predicting virologic failure was assessed in 248 antiretroviral-naive HIV-positive patients who began a PR inhibitor-containing antiretroviral regimen. Genotypic testing was performed on plasma samples stored before the start of therapy. Twenty-seven patients (10.9%) had mutations in the RT, 5 (2%) carried primary mutations in the PR, and 131 (52.8%) showed only secondary PR mutations. Virologic failure at week 24 occurred in 62 (25.0%) of 248 patients. There was a statistically significant correlation between virologic failure and the number of PR mutations (P= .04, chi(2) test). Mutations at codons 10 and 36 of PR (present in 39.3% and 40.0% of patients in whom treatment failed, respectively) were identified by stepwise logistic regression as the strongest predictors of virologic failure (odds ratio, 2.20; 95% confidence interval, 1.30-3.75; P= .004). If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy.
Perno
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CF
Istituto di Ricovero e Cura a Carattere Scientifico L. Spallanzani, and Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy. cf.perno@uniroma2.it
Cozzi-Lepri
A
A
Balotta
C
C
Forbici
F
F
Violin
M
M
Bertoli
A
A
Facchi
G
G
Pezzotti
P
P
Cadeo
G
G
Tositti
G
G
Pasquinucci
S
S
Pauluzzi
S
S
Scalzini
A
A
Salassa
B
B
Vincenti
A
A
Phillips
A N
AN
Dianzani
F
F
Appice
A
A
Angarano
G
G
Monno
L
L
Ippolito
G
G
Moroni
M
M
d' Arminio Monforte
A
A
D000208:Acute Disease; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000627:therapeutic use; D002908:Chronic Disease; D015331:Cohort Studies; D019992:Databases as Topic; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission; D016333:HIV Protease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D016017:Odds Ratio; D017211:Treatment Failure
D000998:Antiviral Agents; D016333:HIV Protease