Virologic response to lopinavir-ritonavir-based antiretroviral regimens in a multicenter international clinical cohort: comparison of genotypic interpretation scores.
Several genotypic interpretation scores have been proposed for the evaluation of susceptibility to lopinavir/ritonavir (LPV/r) but have not been compared using an independent data set. This study was a retrospective multicenter cohort of patients initiating LPV/r-based therapy. The virologic response (VR) was defined as a viral load of <500 copies/ml at week 24. The genotypic interpretation scores surveyed were the LPV mutation score, the ViroLogic score, the ATU score, the Stanford database score, and the International AIDS Society-USA mutation list. Of the 103 patients included in the analysis, 76% achieved VR at 24 weeks. For scores with clinical breakpoints defined (LPV mutation, ATU, ViroLogic, and Stanford), over 80% of the patients below the breakpoints achieved VR, while 50% or less above the breakpoints responded. Protease mutations at positions 10, 54, and 82 and at positions 54, 84, and 90 were associated with a lack of VR in the univariate and multivariate analyses, respectively. The area under the receiver-operator characteristic curves for the five genotypic interpretation scores studied ranged from 0.73 to 0.76. The study confirms that the currently available genotypic interpretation scores which are widely used by clinicians performed similarly well and can be effectively used to predict the virologic activity of LPV/r in treatment-experienced patients.
Grant
Philip
P
Stanford University, Palo Alto, California, USA. pmgrant@stanford.edu
Wong
Eric C
EC
Rode
Richard
R
Shafer
Robert
R
De Luca
Andrea
A
Nadler
Jeffrey
J
Hawkins
Trevor
T
Cohen
Calvin
C
Harrington
Robert
R
Kempf
Dale
D
Zolopa
Andrew
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D005814:Genes, Viral; D005838:Genotype; D006678:HIV / Q000187:drug effects / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D017320:HIV Protease Inhibitors / Q000008:administration & dosage*; D006801:Humans; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011744:Pyrimidinones / Q000008:administration & dosage*; D012189:Retrospective Studies; D019438:Ritonavir / Q000008:administration & dosage*; D055815:Young Adult
D017320:HIV Protease Inhibitors; D011744:Pyrimidinones; D061466:Lopinavir; D019438:Ritonavir