HIV susceptibility to amprenavir: phenotype-based versus rules-based interpretations.
OBJECTIVE
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.
Scudeller
Luigia
L
Institute of Infectious Diseases, University of Udine, Udine.
Torti
Carlo
C
Quiros-Roldan
Eugenia
E
Patroni
Andrea
A
Lo Caputo
Sergio
S
Moretti
Francesca
F
Mazzotta
Francesco
F
Donati
Elisa
E
Vivarelli
Angela
A
Carosi
Giampiero
G
D000465:Algorithms; D002219:Carbamates; D024882:Drug Resistance, Viral / Q000235:genetics*; D005663:Furans; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D016333:HIV Protease / Q000235:genetics; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D010641:Phenotype; D011446:Prospective Studies; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D002219:Carbamates; D005663:Furans; D017320:HIV Protease Inhibitors; D013449:Sulfonamides; C095108:amprenavir; D016333:HIV Protease