The ability of four genotypic interpretation systems to predict virological response to ritonavir-boosted protease inhibitors

Background: Limited information exists on the prognostic value of genotypic interpretation systems (GISs) for ritonavir-boosted protease inhibitors (PI/rs). We compared PI/r resistance levels ascribed by four GIS and examined their abilities to predict HIV-RNA reductions after starting a PI/r-based regimen (baseline). Methods: Data on viraemic (HIV-RNA > 500 copies/ml) patients starting a PI/r with a baseline resistance test were combined from an observational cohort study (EuroSIDA) and three randomized trials (MaxCmin1; MaxCmin2 and COLATE). The GIS surveyed were ANRS, DMC, REGA and Stanford. Factors associated with HlV-RNA change were identified through censored regression analysis. Results: We included 744 patients, of whom 67% were PI experienced. At baseline 12-28% (depending on the GIS) patients had a virus with predicted resistance/ intermediate resistance to the PI/r initiated. Concordance between GISs on ascribed PI/r resistance levels was moderate: kappa values ranged from 0.01 to 1.00, with the lowest kappas seen for amprenavir. The median (interquartile range) baseline HIV-RNA was 4.4 (3.5-5.1) log(10) and was reduced by 2.2 (2.1 -2.3) log(10) 12 (9-13) weeks after baseline. GIS consistently showed greater HlV-RNA reductions as the ascribed level of sensitivity to the PI/r increased. Conversely, the number of other active drugs in the rest of the regimen, according to each GIS did not predict HlV-RNA reductions consistently. Conclusion: Despite large variations in how GIS classify HIV susceptibility to PI/r, all GIS predicted HlV-RNA reductions of a similar magnitude. The ascribed level of susceptibility to other drugs in the regimen did not predict HlV-RNA decline. (C) 2007 Lippincott Williams & Wilkins.