Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice

Salvatrice Mancuso, Simona Di Giambenedetto, Monica Pecorari, Valeria Ghisetti, Paola Corsi, Maurizio Zazzi, Maria Rita Gismondo, Patrizia Bagnarelli, Tiziana Carli, Laura Monno, Andrea De Luca, Grazia Punzi, Mattia C.F. Prosperi, Genny Meini, Grazia Colao, Stefano Bonora

Risultato della ricerca: Article

4 Citazioni (Scopus)

Abstract

Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95%CI 1.10-2.92 per 1 - log10 increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P < 0.001) as independent predictors of HIV-1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996-2003, 2010. © 2010 Wiley-Liss, Inc.
Lingua originaleEnglish
pagine (da-a)1996-2003
Numero di pagine8
RivistaJournal of Medical Virology
Volume82
Stato di pubblicazionePublished - 2010

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Lopinavir
HIV Protease Inhibitors
Ritonavir
HIV-1
Maintenance
Viral Load
RNA
Tenofovir
Protease Inhibitors
Nucleosides
Therapeutics
Genotype
Clinical Trials
Heterosexuality
Survival Analysis
Patient Compliance
Proportional Hazards Models
Human immunodeficiency virus 1 p16 protease
Cohort Studies
Databases

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

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Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice. / Mancuso, Salvatrice; Di Giambenedetto, Simona; Pecorari, Monica; Ghisetti, Valeria; Corsi, Paola; Zazzi, Maurizio; Gismondo, Maria Rita; Bagnarelli, Patrizia; Carli, Tiziana; Monno, Laura; De Luca, Andrea; Punzi, Grazia; Prosperi, Mattia C.F.; Meini, Genny; Colao, Grazia; Bonora, Stefano.

In: Journal of Medical Virology, Vol. 82, 2010, pag. 1996-2003.

Risultato della ricerca: Article

Mancuso, S, Di Giambenedetto, S, Pecorari, M, Ghisetti, V, Corsi, P, Zazzi, M, Gismondo, MR, Bagnarelli, P, Carli, T, Monno, L, De Luca, A, Punzi, G, Prosperi, MCF, Meini, G, Colao, G & Bonora, S 2010, 'Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice', Journal of Medical Virology, vol. 82, pagg. 1996-2003.
Mancuso, Salvatrice ; Di Giambenedetto, Simona ; Pecorari, Monica ; Ghisetti, Valeria ; Corsi, Paola ; Zazzi, Maurizio ; Gismondo, Maria Rita ; Bagnarelli, Patrizia ; Carli, Tiziana ; Monno, Laura ; De Luca, Andrea ; Punzi, Grazia ; Prosperi, Mattia C.F. ; Meini, Genny ; Colao, Grazia ; Bonora, Stefano. / Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice. In: Journal of Medical Virology. 2010 ; Vol. 82. pagg. 1996-2003.
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abstract = "Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1{\%}) and 43 (7.8{\%}) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95{\%}CI 1.10-2.92 per 1 - log10 increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95{\%}CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P < 0.001) as independent predictors of HIV-1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996-2003, 2010. {\circledC} 2010 Wiley-Liss, Inc.",
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TY - JOUR

T1 - Low rate of virological failure and maintenance of susceptibility to HIV-1 protease inhibitors with first-line lopinavir/ritonavir-based antiretroviral treatment in clinical practice

AU - Mancuso, Salvatrice

AU - Di Giambenedetto, Simona

AU - Pecorari, Monica

AU - Ghisetti, Valeria

AU - Corsi, Paola

AU - Zazzi, Maurizio

AU - Gismondo, Maria Rita

AU - Bagnarelli, Patrizia

AU - Carli, Tiziana

AU - Monno, Laura

AU - De Luca, Andrea

AU - Punzi, Grazia

AU - Prosperi, Mattia C.F.

AU - Meini, Genny

AU - Colao, Grazia

AU - Bonora, Stefano

PY - 2010

Y1 - 2010

N2 - Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95%CI 1.10-2.92 per 1 - log10 increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P < 0.001) as independent predictors of HIV-1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996-2003, 2010. © 2010 Wiley-Liss, Inc.

AB - Protease inhibitor (PI)-resistant HIV-1 has hardly ever been detected at failed boosted PI-based first-line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first-line lopinavir/ritonavir (LPV/rtv)-based therapy with available baseline HIV-1 RNA load, a viral genotype and follow-up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV-1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV-1 RNA (RH 1.79, 95%CI 1.10-2.92 per 1 - log10 increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02-1.06 per 10-point increase using the Stanford HIVdb algorithm, P < 0.001) as independent predictors of HIV-1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50-copy and/or 500-copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow-up HIV-1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996-2003, 2010. © 2010 Wiley-Liss, Inc.

KW - Antiretroviral drug resistance; Boosted protease inhibitor; First-line antiretroviral therapy; Human immunodeficiency virus type 1; Lopinavir/ritonavir; Virologic failure; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Cohort Studies; Drug Therap

UR - http://hdl.handle.net/10447/215333

M3 - Article

VL - 82

SP - 1996

EP - 2003

JO - Journal of Medical Virology

JF - Journal of Medical Virology

SN - 0146-6615

ER -