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 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.


CONCLUSIONS
: 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.
Fox
Zoe V
ZV
Copenhagen HIV Programme, Medical Faculty at University of Copenhagen, Denmark. z.fox@pcps.ucl.ac.uk
Geretti
Anna Maria
AM
Kjaer
Jesper
J
Dragsted
Ulrik Bak
UB
Phillips
Andrew N
AN
Gerstoft
Jan
J
Staszewski
Schlomo
S
Clotet
Bonaventura
B
von Wyl
Viktor
V
Lundgren
Jens D
JD
D000328:Adult; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011480:Protease Inhibitors / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use*; D019562:Viral Load
D017320:HIV Protease Inhibitors; D011480:Protease Inhibitors; D012367:RNA, Viral; D019438:Ritonavir