title: Refining criteria for selecting candidates for a safe lopinavir/ritonavir or darunavir/ritonavir monotherapy in HIV-infected virologically suppressed patients.
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).
  
  
  METHODS
  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.
authors.affiliation: San Raffaele Hospital, Milano, Italy.
authors.forename: Nicola
authors.identifier: http://orcid.org/0000-0002-7182-5080
authors.initials: N
authors.lastname: Gianotti
authors.affiliation: University College London, London, United Kingdom.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cozzi-Lepri
authors.affiliation: National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Roma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Antinori
authors.affiliation: San Raffaele Hospital, Milano, Italy.|Università Vita-Salute San Raffaele, Milano, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.affiliation: University of Siena, Siena, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: De Luca
authors.affiliation: University of Catania, Catania, Italy.
authors.forename: Benedetto Maurizio
authors.initials: BM
authors.lastname: Celesia
authors.affiliation: Luigi Sacco Hospital, Milano, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Galli
authors.affiliation: University of Modena, Modena, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mussini
authors.affiliation: National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS, Roma, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Pinnetti
authors.affiliation: San Raffaele Hospital, Milano, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Spagnuolo
authors.affiliation: San Paolo Hospital, Milano, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: d'Arminio Monforte
authors.affiliation: University of Rome Tor Vergata, Roma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.affiliation: University of Rome Tor Vergata, Roma, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Andreoni
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D000069454:Darunavir / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D016016:Proportional Hazards Models; D012367:RNA, Viral / Q000235:genetics; D019438:Ritonavir / Q000627:therapeutic use*; D019562:Viral Load; D014766:Viremia / Q000097:blood / Q000235:genetics; D055815:Young Adult
chemical_list: D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D061466:Lopinavir; D019438:Ritonavir; D000069454:Darunavir