Clinical Validation of Saquinavir/Ritonavir Genotypic Resistance Score in Protease-Inhibitor-Experienced Patients

Abstract

ObjectiveTo 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.MethodsOne-hundred and fifty-one PI-experienced patients receiving a SQV/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) non-parametric test to retain the group of mutations most strongly associated with VR.ResultsAmong the 138 patients with detectable plasma SQV, the median VR was -1.48 [range: -4 to +1.2] log10copies/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 log10copies/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.ConclusionWith this resistance score to SQV/r, the isolates were classified as having no evidence of resistance (0–2), possible resistance (3) or resistance (≥4) by grouping the number of mutations in samples for which the viral load reduction was similar.