title: Lopinavir/r no longer recommended as a first-line regimen: a comparative effectiveness analysis.
abstract: BACKGROUND
  We compared the effectiveness of tenofovir/emtricitabine (TDF/FTC) combined with either lopinavir/r (LPV/r) or another recommended third drug in the 2010 French guidelines in antiretroviral-naïve patients starting combination antiretroviral therapy in 2004-2008 in the French Hospital Database on HIV.
  
  
  METHODS
  The outcomes were stop or switch of the third component, viral load (VL) <500 copies/ml, an increase of at least 100 CD4 cells/mm(3), AIDS-defining event and non-AIDS-defining hospitalization or death. Propensity scores were estimated by logistic regression based on the clinical centre and other confounders. In each clinical centre, each patient initiating LPV/r was matched with a patient initiating another third drug (efavirenz or atazanavir/r) and having a close propensity score. Cox's proportional hazards models were then used, with treatment as covariate. Time was right-censored at four years.
  
  
  RESULTS
  1269 patients started LPV/r plus TDF/FTC, and 890 could be matched to 890 patients receiving another third drug. Baseline characteristics were well balanced between these two groups. LPV/r was associated with a higher risk of third drug stop (hazard ratio (HR): 1.69; 95% confidence interval (CI), 1.42-2.00) and with less rapid viral suppression (HR: 0.83; 95% CI, 0.72-0.95). There was no difference in the time required for a CD4 cell increment of at least 100/mm(3), or to the occurrence of an AIDS-defining event. Non-AIDS-defining hospitalizations or deaths were more frequent with LPV/r (HR: 1.79; 95% CI, 1.33-2.39).
  
  
  CONCLUSIONS
  For first-line therapy, in this observational setting, TDF/FTC plus LPV/r were less durable than TDF/FTC plus another recommended third drug, led to a less rapid viral suppression and were associated with a higher risk of non-AIDS morbidity.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; INSERM Transfert, Paris, France; valerie.potard@ccde.chups.jussieu.fr.
authors.forename: Valérie
authors.initials: V
authors.lastname: Potard
authors.affiliation: Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: David
authors.initials: D
authors.lastname: Rey
authors.affiliation: Aix Marseille Univ, APHM Sainte-Marguerite, Service d'Immuno-hématologie clinique, INSERM U912 (SESSTIM) Marseille, Marseille, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Poizot-Martin
authors.affiliation: Service de maladies infectieuses et tropicales Hôpital Nord AP-HM, Marseille, Marseille, France.
authors.forename: Saadia
authors.initials: S
authors.lastname: Mokhtari
authors.affiliation: Département de Santé Publique, CHU Nice, Nice, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Pradier
authors.affiliation: St-Louis CHU Paris, AP-HP, UPMC Univ Paris 06, Paris, France.
authors.forename: Willy
authors.initials: W
authors.lastname: Rozenbaum
authors.affiliation: Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Université Paris Diderot, Paris, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Brun-Vezinet
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France; INSERM, UMR_S 1136, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Costagliola
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000068679:Emtricitabine; D005260:Female; D005602:France; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D061466:Lopinavir / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D011446:Prospective Studies; D000068698:Tenofovir; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D061466:Lopinavir; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine
keywords: HIV infection; antiretroviral therapy; effectiveness; first-line therapy; propensity score