title: Dual treatment with lopinavir-ritonavir plus lamivudine versus triple treatment with lopinavir-ritonavir plus lamivudine or emtricitabine and a second nucleos(t)ide reverse transcriptase inhibitor for maintenance of HIV-1 viral suppression (OLE): a randomised, open-label, non-inferiority trial.
abstract: BACKGROUND
  Our objective was to assess therapeutic non-inferiority of dual treatment with lopinavir-ritonavir and lamivudine to triple treatment with lopinavir-ritonavir plus two nucleos(t)ides for maintenance of HIV-1 viral suppression.
  
  
  METHODS
  In this randomised, open-label, non-inferiority trial, we recruited patients from 32 HIV units in hospitals in Spain and France. Eligible patients were HIV-infected adults (aged ≥18 years) with HIV-1 RNA of less than 50 copies per mL, for at least 6 months on triple treatment with lopinavir-ritonavir (twice daily) plus lamivudine or emtricitabine and a second nucleos(t)ide, with no resistance or virological failure to these drugs, and no positive hepatitis B serum surface antigen. Investigators at each centre randomly assigned patients (1:1; block size of four; stratified by time to suppression [<1 year or >1 year] and nadir CD4 cell count [<100 cells per μL or >100 cells per μL]; computer-generated random sequence) to continue triple treatment or switch to dual treatment (oral lopinavir 400 mg and oral ritonavir 100 mg twice daily plus oral lamivudine 300 mg once daily). The primary endpoint was response to treatment in the intention-to-treat population (all randomised patients) at 48 weeks. The non-inferiority margin was 12%. This study is registered with ClinicalTrials.gov, number NCT01471821.
  
  
  RESULTS
  Between Oct 1, 2011, and April 1, 2013, we randomly assigned 250 participants to continue triple treatment (127 [51%] patients) or switch to dual treatment (123 [49%] patients). In the intention-to-treat population, 110 (86·6%) of 127 patients in the triple-treatment group responded to treatment versus 108 (87·8%) of 123 in the dual-treatment group (difference -1·2% [95% CI -9·6 to 7·3]; p=0·92), meeting the criteria for non-inferiority. Serious adverse events occurred in eight (7%) patients in the triple-treatment group and five (4%) in the dual-treatment group (p=0·515), and study drug discontinuations due to adverse events occurred in four (3%) in the triple-treatment group and one (1%) in the dual-treatment group (p=0·223).
  
  
  CONCLUSIONS
  Dual treatment with lopinavir-ritonavir plus lamivudine has non-inferior therapeutic efficacy and is similarly tolerated to triple treatment.
  
  
  BACKGROUND
  AbbVie and Red Temática Cooperativa de Investigación en Sida.
authors.affiliation: Hospital La Paz, Instituto de Investigation Sanitaria del Hospital Universitario La Paz, Madrid, Spain. Electronic address: joser.arribas@salud.madrid.org.
authors.forename: José R
authors.initials: JR
authors.lastname: Arribas
authors.affiliation: Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris, Institut National de la Santé et de la Recherche Médicale UMR_S 1136, Paris, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.affiliation: Hôpital Bichat-Claude Bernard, AP-HP, and Institut National de la Santé et de la Recherche Médicale UMR 1137, Paris, France.
authors.forename: Roland
authors.initials: R
authors.lastname: Landman
authors.affiliation: Hospital Clínic/Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Judit
authors.initials: J
authors.lastname: Pich
authors.affiliation: Hospital Clínic/Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Mallolas
authors.affiliation: Hospital Clínic/Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Martínez-Rebollar
authors.affiliation: Hospital La Paz, Instituto de Investigation Sanitaria del Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Zamora
authors.affiliation: Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Estrada
authors.affiliation: Hospital Vall d'Hebrón, Barcelona, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Crespo
authors.affiliation: Hospital Universitario de Bellvitge, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Podzamczer
authors.affiliation: Hospital General Universitario de Alicante, Alicante, Spain.
authors.forename: Joaquín
authors.initials: J
authors.lastname: Portilla
authors.affiliation: Hospital Universitario Ramón y Cajal, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Dronda
authors.affiliation: Hospital de Donostia, Donostia, Spain.
authors.forename: José A
authors.initials: JA
authors.lastname: Iribarren
authors.affiliation: Hospital de Sant Pau, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.affiliation: Hospital Universitario Doce de Octubre, i+12, Madrid, Spain.
authors.forename: Federico
authors.initials: F
authors.lastname: Pulido
authors.affiliation: Hospital La Fe, Valencia, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Montero
authors.affiliation: Hospital del Mar, Barcelona, Spain.
authors.forename: Hernando
authors.initials: H
authors.lastname: Knobel
authors.affiliation: CHU de Martinique-Institut National de la Santé et de la Recherche Médicale CIC1224, Fort-de-France, France.
authors.forename: André
authors.initials: A
authors.lastname: Cabié
authors.affiliation: Assistance Publique - Hôpitaux de Paris, Hôpital Européen Georges Pompidou, and Université Paris Descartes, Sorbonne Paris-Cité, Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Weiss
authors.affiliation: Hospital Clínic/Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D057194:Intention to Treat Analysis; D019259:Lamivudine / Q000627:therapeutic use; D061466:Lopinavir / Q000627:therapeutic use; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000097:blood*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D061466:Lopinavir; D019259:Lamivudine; D000068679:Emtricitabine; D019438:Ritonavir