Clinical validation of saquinavir/ritonavir genotypic resistance score in protease-inhibitor-experienced patients

Abstract

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.

Conclusion: 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.