Refining criteria for selecting candidates for a safe lopinavir/ritonavir or darunavir/ritonavir monotherapy in HIV-infected virologically suppressed patients

Nicola Gianotti, Alessandro Cozzi-Lepri, Andrea Antinori, Antonella Castagna, Andrea De Luca, Benedetto Maurizio Celesia, Massimo Galli, Cristina Mussini, Carmela Pinnetti, Vincenzo Spagnuolo, Antonella D'Arminio Monforte, Francesca Ceccherini-Silberstein, Massimo Andreoni

Research output: Contribution to journalArticle

Abstract

Objective: The primary objective of this study was to estimate the incidence of treatment failure (TF) to protease inhibitor monotherapies (PI/r-MT) with lopinavir/ritonavir (LPV/r) or darunavir/ritonavir (DRV/r). Design: A multicenter cohort of HIV-infected patients with viral load (VL) ≤50 copies/mL, who underwent a switch from any triple combination therapy to PI/r-MT with either LPV/r or DRV/r. Methods: VL was assessed in each center according to local procedures. Residual viremia was defined by any HIV-RNA value detectable below 50 copies/mL by a Real-Time PCR method. Standard survival analysis was used to estimate the rate of TF (defined by virological failure or interruption of monotherapy or reintroduction of combination therapy). A multivariable Cox regression analysis with automatic stepwise procedures was used to identify factors independently associated with TF among nadir and baseline CD4+ counts, residual viremia, time spent with <50 HIV-RNA copies/mL before switch, history of virological failure, HCV co-infection, being on a PI/r and hemoglobin concentrations at baseline. Results: Six hundred ninety patients fulfilled the inclusion criteria and were included in this analysis. Their median follow-up was 20 (10-37) months. By month 36, TF occurred in 176 (30.2%; 95% CI:25.9-34.5) patients. Only CD4+ nadir counts (adjusted hazard ratio [aHR] = 2.03 [95% CI: 1.35, 3.07] for counts ≤100 vs. >100 cells/μL) and residual viremia (aHR = 1.48 [95% CI: 1.01-2.17] vs. undetectable VL) were independently associated to TF. Conclusions: Residual viremia and nadir CD4+ counts <100 cells/μL should be regarded as the main factors to be taken into account before considering switching to a PI/r-MT.

Original languageEnglish
Article numbere0171611
JournalPLoS One
Volume12
Issue number2
DOIs
Publication statusPublished - Feb 1 2017

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Lopinavir
Ritonavir
Viremia
viremia
refining
Treatment Failure
Refining
viral load
proteinase inhibitors
Protease Inhibitors
Viral Load
HIV
CD4 Lymphocyte Count
therapeutics
Survival Analysis
Regression analysis
Real-Time Polymerase Chain Reaction
quantitative polymerase chain reaction
regression analysis
Switches

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Refining criteria for selecting candidates for a safe lopinavir/ritonavir or darunavir/ritonavir monotherapy in HIV-infected virologically suppressed patients. / Gianotti, Nicola; Cozzi-Lepri, Alessandro; Antinori, Andrea; Castagna, Antonella; De Luca, Andrea; Celesia, Benedetto Maurizio; Galli, Massimo; Mussini, Cristina; Pinnetti, Carmela; Spagnuolo, Vincenzo; D'Arminio Monforte, Antonella; Ceccherini-Silberstein, Francesca; Andreoni, Massimo.

In: PLoS One, Vol. 12, No. 2, e0171611, 01.02.2017.

Research output: Contribution to journalArticle

Gianotti, Nicola ; Cozzi-Lepri, Alessandro ; Antinori, Andrea ; Castagna, Antonella ; De Luca, Andrea ; Celesia, Benedetto Maurizio ; Galli, Massimo ; Mussini, Cristina ; Pinnetti, Carmela ; Spagnuolo, Vincenzo ; D'Arminio Monforte, Antonella ; Ceccherini-Silberstein, Francesca ; Andreoni, Massimo. / Refining criteria for selecting candidates for a safe lopinavir/ritonavir or darunavir/ritonavir monotherapy in HIV-infected virologically suppressed patients. In: PLoS One. 2017 ; Vol. 12, No. 2.
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abstract = "Objective: The primary objective of this study was to estimate the incidence of treatment failure (TF) to protease inhibitor monotherapies (PI/r-MT) with lopinavir/ritonavir (LPV/r) or darunavir/ritonavir (DRV/r). Design: A multicenter cohort of HIV-infected patients with viral load (VL) ≤50 copies/mL, who underwent a switch from any triple combination therapy to PI/r-MT with either LPV/r or DRV/r. Methods: VL was assessed in each center according to local procedures. Residual viremia was defined by any HIV-RNA value detectable below 50 copies/mL by a Real-Time PCR method. Standard survival analysis was used to estimate the rate of TF (defined by virological failure or interruption of monotherapy or reintroduction of combination therapy). A multivariable Cox regression analysis with automatic stepwise procedures was used to identify factors independently associated with TF among nadir and baseline CD4+ counts, residual viremia, time spent with <50 HIV-RNA copies/mL before switch, history of virological failure, HCV co-infection, being on a PI/r and hemoglobin concentrations at baseline. Results: Six hundred ninety patients fulfilled the inclusion criteria and were included in this analysis. Their median follow-up was 20 (10-37) months. By month 36, TF occurred in 176 (30.2{\%}; 95{\%} CI:25.9-34.5) patients. Only CD4+ nadir counts (adjusted hazard ratio [aHR] = 2.03 [95{\%} CI: 1.35, 3.07] for counts ≤100 vs. >100 cells/μL) and residual viremia (aHR = 1.48 [95{\%} CI: 1.01-2.17] vs. undetectable VL) were independently associated to TF. Conclusions: Residual viremia and nadir CD4+ counts <100 cells/μL should be regarded as the main factors to be taken into account before considering switching to a PI/r-MT.",
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AU - Gianotti, Nicola

AU - Cozzi-Lepri, Alessandro

AU - Antinori, Andrea

AU - Castagna, Antonella

AU - De Luca, Andrea

AU - Celesia, Benedetto Maurizio

AU - Galli, Massimo

AU - Mussini, Cristina

AU - Pinnetti, Carmela

AU - Spagnuolo, Vincenzo

AU - D'Arminio Monforte, Antonella

AU - Ceccherini-Silberstein, Francesca

AU - Andreoni, Massimo

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N2 - Objective: The primary objective of this study was to estimate the incidence of treatment failure (TF) to protease inhibitor monotherapies (PI/r-MT) with lopinavir/ritonavir (LPV/r) or darunavir/ritonavir (DRV/r). Design: A multicenter cohort of HIV-infected patients with viral load (VL) ≤50 copies/mL, who underwent a switch from any triple combination therapy to PI/r-MT with either LPV/r or DRV/r. Methods: VL was assessed in each center according to local procedures. Residual viremia was defined by any HIV-RNA value detectable below 50 copies/mL by a Real-Time PCR method. Standard survival analysis was used to estimate the rate of TF (defined by virological failure or interruption of monotherapy or reintroduction of combination therapy). A multivariable Cox regression analysis with automatic stepwise procedures was used to identify factors independently associated with TF among nadir and baseline CD4+ counts, residual viremia, time spent with <50 HIV-RNA copies/mL before switch, history of virological failure, HCV co-infection, being on a PI/r and hemoglobin concentrations at baseline. Results: Six hundred ninety patients fulfilled the inclusion criteria and were included in this analysis. Their median follow-up was 20 (10-37) months. By month 36, TF occurred in 176 (30.2%; 95% CI:25.9-34.5) patients. Only CD4+ nadir counts (adjusted hazard ratio [aHR] = 2.03 [95% CI: 1.35, 3.07] for counts ≤100 vs. >100 cells/μL) and residual viremia (aHR = 1.48 [95% CI: 1.01-2.17] vs. undetectable VL) were independently associated to TF. Conclusions: Residual viremia and nadir CD4+ counts <100 cells/μL should be regarded as the main factors to be taken into account before considering switching to a PI/r-MT.

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