Clinical validation of saquinavir/ritonavir genotypic resistance score in protease-inhibitor-experienced patients.
OBJECTIVE
To identify a genotypic score for resistance to saquinavir boosted with ritonavir (SQV/r; 1,000/100 mg twice daily)-based regimens in protease inhibitor (PI)-experienced patients.


METHODS
One-hundred and fifty-one PI-experienced patients receiving a SOV/r-containing regimen were enrolled retrospectively. The virological response (VR) was defined as the decrease in HIV RNA at months 3-5. The effect of each mutation in the protease gene on the VR to SQV/r regimen was assessed using non-parametric univariate analyses and then a step-by-step analysis was carried out using a Jonckheere-Tepstra (JT) nonparametric test to retain the group of mutations most strongly associated with VR.


RESULTS
Among the 138 patients with detectable plasma SQV, the median VR was -1.48 [range: -4 to +1.2] log10 copies/ml. Changes at 12 codons were associated with a reduced VR to SQV/r: codons 10, 15, 20, 24, 46, 54, 62, 71, 73, 82, 84 and 90. The JT procedure led to selection of the following genotypic score, 10+15+20+ 24+62+73+82+84+90, as providing the strongest association with VR. In the 35 patients with none of the mutations in this score, the median decrease in HIV RNA was -2.24 log10 copies/ml and it was -1.88 (n=29), -1.43 (n=24), -0.52 (n=30), -0.18 (n=9), -0.11 (n=6) and -0.30 (n=5) log10 copies/ml in those with 1, 2, 3, 4, 5 and 6 mutations, respectively.


CONCLUSIONS
With this resistance score to SQV/r, the isolates were classified as having no evidence of resistance (0-2), possible resistance (3) or resistance (> or =4) by grouping the number of mutations in samples for which the viral load reduction was similar.
Marcelin
Anne-Genevieve
AG
Department of Virology, Pitie-Salpftriere Hospital, AP-HP, Universite Pierre et Marie Curie, Paris, France. anne-genevieve.marcelin@psl.aphp.fr
Flandre
Philippe
P
de Mendoza
Carmen
C
Roquebert
Benedicte
B
Peytavin
Gilles
G
Valer
Luisa
L
Wirden
Marc
M
Abbas
Sarah
S
Katlama
Christine
C
Soriano
Vincent
V
Calvez
Vincent
V
D003062:Codon; D024921:Drug Resistance, Multiple, Viral / Q000235:genetics*; D004359:Drug Therapy, Combination; D005602:France; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D016333:HIV Protease / Q000235:genetics*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D015233:Models, Statistical; D009154:Mutation; D012367:RNA, Viral / Q000097:blood*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D019438:Ritonavir / Q000627:therapeutic use*; D019258:Saquinavir / Q000627:therapeutic use*; D013030:Spain; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load
D003062:Codon; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D016333:HIV Protease; D019258:Saquinavir; D019438:Ritonavir