Clinical Evaluation of Rega 8: An Updated Genotypic Interpretation System That Significantly Predicts HIV-Therapy Response

Jurgen Vercauteren, Gertjan Beheydt, Mattia Prosperi, Pieter Libin, Stijn Imbrechts, Ricardo Camacho, Bonaventura Clotet, Andrea De Luca, Zehava Grossman, Rolf Kaiser, Anders Sönnerborg, Carlo Torti, Eric Van Wijngaerden, Jean Claude Schmit, Maurizio Zazzi, Anna Maria Geretti, Anne Mieke Vandamme, Kristel Van Laethem

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Introduction:Clinically evaluating genotypic interpretation systems is essential to provide optimal guidance in designing potent individualized HIV-regimens. This study aimed at investigating the ability of the latest Rega algorithm to predict virological response on a short and longer period.Materials & Methods:9231 treatment changes episodes were extracted from an integrated patient database. The virological response after 8, 24 and 48 weeks was dichotomized to success and failure. Success was defined as a viral load below 50 copies/ml or alternatively, a 2 log decrease from the baseline viral load at 8 weeks. The predictive ability of Rega version 8 was analysed in comparison with that of previous evaluated version Rega 5 and two other algorithms (ANRS v2011.05 and Stanford HIVdb v6.0.11). A logistic model based on the genotypic susceptibility score was used to predict virological response, and additionally, confounding factors were added to the model. Performance of the models was compared using the area under the ROC curve (AUC) and a Wilcoxon signed-rank test.Results:Per unit increase of the GSS reported by Rega 8, the odds on having a successful therapy response on week 8 increased significantly by 81% (OR = 1.81, CI = [1.76-1.86]), on week 24 by 73% (OR = 1.73, CI = [1.69-1.78]) and on week 48 by 85% (OR = 1.85, CI = [1.80-1.91]). No significant differences in AUC were found between the performance of Rega 8 and Rega 5, ANRS v2011.05 and Stanford HIVdb v6.0.11, however Rega 8 had the highest sensitivity: 76.9%, 76.5% and 77.2% on 8, 24 and 48 weeks respectively. Inclusion of additional factors increased the performance significantly.Conclusion:Rega 8 is a significant predictor for virological response with a better sensitivity than previously, and with rules for recently approved drugs. Additional variables should be taken into account to ensure an effective regimen. © 2013 Vercauteren et al.
    Original languageEnglish
    Article numbere61436
    JournalPLoS ONE
    Volume8
    Issue number4
    DOIs
    Publication statusPublished - 17 Apr 2013

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