JAC Advance Access published online on October 16, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg456
© 2003 by The British Society for Antimicrobial Chemotherapy
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original article
1 Institute of Infectious
Diseases, University of Udine, Udine;
* Corresponding author. E-mail: carlotorti{at}hotmail.com.
Received 25 March 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
HIV susceptibility to amprenavir: phenotype-based
versus rules-based interpretations
2 Institute of Infectious and Tropical Diseases, University
of Brescia, P. le Spedali Civili, 1, 25123 Brescia;
3 Institute of Infectious and Tropical Diseases, University
of Brescia, P. le Spedali Civili, 1, 25123 Brescia; 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
CiteULike 
Connotea 
Del.icio.us What's this?