title: Secondary mutations in the protease region of human immunodeficiency virus and virologic failure in drug-naive patients treated with protease inhibitor-based therapy.
abstract: 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.
authors.affiliation: 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
authors.forename: C F
authors.initials: CF
authors.lastname: Perno
authors.forename: A
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.forename: C
authors.initials: C
authors.lastname: Balotta
authors.forename: F
authors.initials: F
authors.lastname: Forbici
authors.forename: M
authors.initials: M
authors.lastname: Violin
authors.forename: A
authors.initials: A
authors.lastname: Bertoli
authors.forename: G
authors.initials: G
authors.lastname: Facchi
authors.forename: P
authors.initials: P
authors.lastname: Pezzotti
authors.forename: G
authors.initials: G
authors.lastname: Cadeo
authors.forename: G
authors.initials: G
authors.lastname: Tositti
authors.forename: S
authors.initials: S
authors.lastname: Pasquinucci
authors.forename: S
authors.initials: S
authors.lastname: Pauluzzi
authors.forename: A
authors.initials: A
authors.lastname: Scalzini
authors.forename: B
authors.initials: B
authors.lastname: Salassa
authors.forename: A
authors.initials: A
authors.lastname: Vincenti
authors.forename: A N
authors.initials: AN
authors.lastname: Phillips
authors.forename: F
authors.initials: F
authors.lastname: Dianzani
authors.forename: A
authors.initials: A
authors.lastname: Appice
authors.forename: G
authors.initials: G
authors.lastname: Angarano
authors.forename: L
authors.initials: L
authors.lastname: Monno
authors.forename: G
authors.initials: G
authors.lastname: Ippolito
authors.forename: M
authors.initials: M
authors.lastname: Moroni
authors.forename: A
authors.initials: A
authors.lastname: d' Arminio Monforte
mesh_terms: 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
chemical_list: D000998:Antiviral Agents; D016333:HIV Protease