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 - Prosperi, Mattia C.F.
AU - Meini, Genny
AU - Colao, Grazia
AU - Bonora, Stefano
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
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
KW - Combination; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lopinavir; Male; Pyrimidinones; RNA
KW - Highly Active; Cohort Studies; Drug Therapy
KW - Viral; Reverse Transcriptase Inhibitors; Ritonavir; Survival Analysis; Treatment Failure; Treatment Outcome; Viral Load; Drug Resistance
KW - Viral; Virology; Infectious Diseases
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
KW - Combination; Female; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Lopinavir; Male; Pyrimidinones; RNA
KW - Highly Active; Cohort Studies; Drug Therapy
KW - Viral; Reverse Transcriptase Inhibitors; Ritonavir; Survival Analysis; Treatment Failure; Treatment Outcome; Viral Load; Drug Resistance
KW - Viral; Virology; Infectious Diseases
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 -