HIV susceptibility to amprenavir: Phenotype-based versus rules-based interpretations

Luigia Scudeller, Carlo Torti, Eugenia Quiros-Roldan, Andrea Patroni, Sergio Lo Caputo, Francesca Moretti, Francesco Mazzotta, Elisa Donati, Angela Vivarelli, Giampiero Carosi, P. Pierotti, G. Carosi, F. Castelli, L. Tomasoni, C. Carnevale, A. Pan, R. Maserati, L. Minoli, A. Poggio, V. MondinoM. Toti, E. Donati, F. Alberici, M. Sisti, G. Cadeo, D. Vangi, A. Chirianni, A. Loiacono, A. Lazzarin, N. Gianotti, F. Leoncini, M. Pozzi, V. Vullo, G. Pastore, N. Ladisa, D. Dionisio, A. Scasso, M. De Gennaro, F. Resta, G. Buccoliero, P. Delle Foglie, F. Ghinelli, L. Sighinolfi, G. Angarano, C. Tinelli

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: The objective was to study genotypic correlates of discordant interpretations of amprenavir (APV) resistance between a rules-based algorithm and either recombinant phenotype or virtual phenotype. Methods: HIV resistance mutations found in patients from the GenPheRex study were interpreted with VGI-TRUGENE (version 5.0; VGI) and compared with either recombinant-phenotype (Antivirogram, r-PHT) or virtual-phenotype (Virtual-Phenotype, v-PHT) interpreted through Virco biological cut-offs. Results: Among 180 samples available, 56 (31.1%) were discordant with the observed genotype interpretation results, as a result of being judged as sensitive by r-PHT or v-PHT but resistant by VGI (S/R). Only the I84V mutation was almost invariably found in concordant resistant isolates compared with S/R isolates (60% versus 0%, respectively; P <0.0001). Notwithstanding this, the number of multi-protease inhibitor-associated mutations (PAMs) was significantly higher in the concordant resistant isolates; the prevalence of >3 PAMs was 56.52% versus 33.93% in R/R and S/R isolates, respectively (P = 0.01). Correspondence analysis confirmed the relevance of PAMs, although additional mutations appeared to be correlated with APV resistance. Conclusions: The rate of discordance between rules-based and either r-PHT or v-PHT interpretations for APV was high. Mutation I84V and accumulation of >3 PAMs were found to be associated with resistance as interpreted with all systems tested. However, our results indicate that a number of mutations may have an impact on APV resistance, but that they are missed by current interpretation algorithms and this merits further investigations.

Original languageEnglish
Pages (from-to)776-781
Number of pages6
JournalJournal of Antimicrobial Chemotherapy
Volume52
Issue number5
DOIs
Publication statusPublished - Nov 2003

Keywords

  • Discordances
  • Genotyping
  • Mutations
  • Phenotyping

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology

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