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-log(10) 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.

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 / M.C. Frosperi, M. Zazzi, G. Punzi, L. Monno, G. Colao, P. Corsi, S. Di Giambenedetto, G. Meini, V. Ghisetti, S. Bonora, M. Pecorari, M.R. Gismondo, P. Bagnarelli, T. Carli, A. De Luca, ARCA Collaborative Group. - In: JOURNAL OF MEDICAL VIROLOGY. - ISSN 0146-6615. - 82:12(2010 Dec), pp. 1996-2003.

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

M.R. Gismondo;
2010

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-log(10) 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.
English
Antiretroviral drug resistance; Boosted protease inhibitor; First-line antiretroviral therapy; Human immunodeficiency virus type 1; Lopinavir/ritonavir; Virologic failure
Settore MED/07 - Microbiologia e Microbiologia Clinica
Articolo
Sì, ma tipo non specificato
dic-2010
Wiley-Liss
82
12
1996
2003
Pubblicato
Periodico con rilevanza internazionale
info:eu-repo/semantics/article
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 / M.C. Frosperi, M. Zazzi, G. Punzi, L. Monno, G. Colao, P. Corsi, S. Di Giambenedetto, G. Meini, V. Ghisetti, S. Bonora, M. Pecorari, M.R. Gismondo, P. Bagnarelli, T. Carli, A. De Luca, ARCA Collaborative Group. - In: JOURNAL OF MEDICAL VIROLOGY. - ISSN 0146-6615. - 82:12(2010 Dec), pp. 1996-2003.
none
Prodotti della ricerca::01 - Articolo su periodico
16
262
Article (author)
si
M.C. Frosperi, M. Zazzi, G. Punzi, L. Monno, G. Colao, P. Corsi, S. Di Giambenedetto, G. Meini, V. Ghisetti, S. Bonora, M. Pecorari, M.R. Gismondo, ...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/156710
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