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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Highly Active Antiretroviral Therapy
Drug Resistance
HIV-1
Confidence Intervals
Mutation
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology

Cite this

De Luca, A., Cozzi-Lepri, A., Perno, C. F., Balotta, C., Di Giambenedetto, S., Poggio, A., ... 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.

Variability in the interpretation of transmitted genotypic HIV-1 drug resistance and prediction of virological outcomes of the initial HAART by distinct systems. / De Luca, Andrea; Cozzi-Lepri, Alessandro; Perno, Carlo Federico; Balotta, Claudia; Di Giambenedetto, Simona; Poggio, Antonio; Pagano, Gabriella; Tositti, Giulia; Piscopo, Rita; Del Forno, Antonio; Chiodo, Francesco; Magnani, Giacomo; D'Arminio Monforte, Antonella.

In: Antiviral Therapy, Vol. 9, No. 5, 10.2004, p. 743-752.

Research output: Contribution to journalArticle

De Luca, A, Cozzi-Lepri, A, Perno, CF, 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, vol. 9, no. 5, pp. 743-752.
De Luca, Andrea ; Cozzi-Lepri, Alessandro ; Perno, Carlo Federico ; Balotta, Claudia ; Di Giambenedetto, Simona ; Poggio, Antonio ; Pagano, Gabriella ; Tositti, Giulia ; Piscopo, Rita ; Del Forno, Antonio ; Chiodo, Francesco ; Magnani, Giacomo ; D'Arminio Monforte, Antonella. / Variability in the interpretation of transmitted genotypic HIV-1 drug resistance and prediction of virological outcomes of the initial HAART by distinct systems. In: Antiviral Therapy. 2004 ; Vol. 9, No. 5. pp. 743-752.
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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.",
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AU - Balotta, Claudia

AU - Di Giambenedetto, Simona

AU - Poggio, Antonio

AU - Pagano, Gabriella

AU - Tositti, Giulia

AU - Piscopo, Rita

AU - Del Forno, Antonio

AU - Chiodo, Francesco

AU - Magnani, Giacomo

AU - D'Arminio Monforte, Antonella

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