Variability in the interpretation of transmitted genotypic HIV-1 drug resistance and prediction of virological outcomes of the initial HAART by distinct systems

Andrea De Luca, Alessandro Cozzi-Lepri, Carlo Federico Perno, Claudia Balotta, Simona Di Giambenedetto, Antonio Poggio, Gabriella Pagano, Giulia Tositti, Rita Piscopo, Antonio Del Forno, Francesco Chiodo, Giacomo Magnani, Antonella D'Arminio Monforte

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Abstract

High level HIV-1 drug resistance in recently infected treatment-naive individuals correlates with sub-optimal virological responses to highly active antiretroviral therapy (HAART). To determine whether genotypic HIV-1 drug resistance in chronic naive patients, as interpreted by various systems, could predict the virological outcomes of HAART, isolates from patients enrolled in a prospective observational cohort (ICoNA) prior to treatment start were genotyped. Genotypic susceptibility scores (GSS) assigned to the initial HAART regimens using the interpretations of pre-therapy resistance mutations by 13 systems were related to virological outcomes. Of 415 patients, 42 (10%) had at least one major resistance mutation. According to the different interpretations, 1.9-20.5% of patients had some level of resistance to at least one drug in the initial regimen. In multivariable analysis, GSS from two systems significantly predicted the time to virological success: Rega 5.5, for each unit increase in GSS adjusted relative hazard (RH) 1.86 [95% confidence intervals (95% CI): 1.15-3.02] and hivresistanceWeb v3, RH 1.87 (95% CI: 1.00-3.48). With three other systems, GSS showed a trend towards a significant prediction of success: Retrogram 1.6, RH 2.33 (95% CI: 0.98-5.53), Menendez 2002, RH 2.36 (95% CI: 0.97-5.72) and Stanford hivdb, RH 2.06 (95% CI: 0.94-4.49). Genotypic resistance testing coupled with adequate interpretation in chronic naive patients can usefully identify those at risk of sub-optimal virological response to HAART.

Original languageEnglish
Pages (from-to)743-752
Number of pages10
JournalAntiviral Therapy
Volume9
Issue number5
Publication statusPublished - Oct 2004

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ASJC Scopus subject areas

  • Pharmacology

Cite this

De Luca, A., Cozzi-Lepri, A., Perno, C. F., Balotta, C., Di Giambenedetto, S., Poggio, A., Pagano, G., Tositti, G., Piscopo, R., Del Forno, A., Chiodo, F., Magnani, G., & D'Arminio Monforte, A. (2004). Variability in the interpretation of transmitted genotypic HIV-1 drug resistance and prediction of virological outcomes of the initial HAART by distinct systems. Antiviral Therapy, 9(5), 743-752.