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

Fox ZV, Geretti AM, Kjaer J, Dragsted UB, Phillips AN, Gerstoft J, Staszewski S, Clotet B, von Wyl V, Lundgren JD

Copenhagen HIV Programme, Medical Faculty at University of Copenhagen, Denmark. z.fox@pcps.ucl.ac.uk

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 HIV-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) log10 and was reduced by 2.2 (2.1-2.3) log10 12 (9-13) weeks after baseline. GIS consistently showed greater HIV-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 HIV-RNA reductions consistently. CONCLUSION:: Despite large variations in how GIS classify HIV susceptibility to PI/r, all GIS predicted HIV-RNA reductions of a similar magnitude. The ascribed level of susceptibility to other drugs in the regimen did not predict HIV-RNA decline.

Published 21 September 2007 in AIDS, 21(15): 2033-42.
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