JAC Advance Access originally published online on October 16, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Antimicrobial Chemotherapy (2003) 52, 776-781
© 2003 The British Society for Antimicrobial Chemotherapy
HIV susceptibility to amprenavir: phenotype-based versus rules-based interpretations
1 Institute of Infectious Diseases, University of Udine, Udine; 2 Institute of Infectious and Tropical Diseases, University of Brescia, P. le Spedali Civili, 1, 25123 Brescia; 3 Biostatistics Unit, IRCCS Policlinico S. Matteo, Pavia; 4 S.M. Annunziata Hospital, ASL Firenze, Florence; 5 Department of Infectious Diseases, ASL Grosseto, Grosseto; 6 Department of Infectious Diseases, ASL Pistoia, Pistoia, Italy
Received 25 March 2003; returned 10 July 2003; revised 31 July 2003; accepted 22 August 2003
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.
Keywords: genotyping, phenotyping, discordances, mutations
* Corresponding author. Tel: +39-030-3995663; Fax: +39-030-303061; E-mail: carlotorti{at}hotmail.com
GenPheRex Group members are listed in the Acknowledgements.