title: Dual treatment with atazanavir-ritonavir plus lamivudine versus triple treatment with atazanavir-ritonavir plus two nucleos(t)ides in virologically stable patients with HIV-1 (SALT): 48 week results from a randomised, open-label, non-inferiority trial.
abstract: BACKGROUND
  Problems associated with lifelong antiretroviral therapy, such as need for strict adherence, drug-related toxic effects, difficulties with treatment schedules, and cost, mean that simplification strategies should be sought. We aimed to explore the efficacy and safety of dual treatment with atazanavir-ritonavir plus lamivudine as an option to switch to from standard combination antiretroviral therapy in patients with an HIV-1 infection who are virologically suppressed.
  
  
  METHODS
  In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years and older with chronic HIV-1 infection and no previous treatment failure or resistance, and with HIV-1 RNA of less than 50 copies per mL for at least 6 months, negative hepatitis B virus surface antigen, and good general health, from 30 hospitals in Spain. Exclusion criteria were switch in antiretroviral therapy during the previous 4 months, previous virological failure, pregnancy or breastfeeding, Gilbert's syndrome, use of contraindicated drugs, grade 4 laboratory abnormalities, and previous intolerance to any of the study drugs. We randomly assigned patients (1:1; stratified by active hepatitis C virus infection and previous treatment; computer-generated random number sequence) to dual treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus lamivudine (300 mg once daily) or triple treatment with oral atazanavir (300 mg once daily) and ritonavir (100 mg once daily) plus two nucleos(t)ide reverse transcriptase inhibitors at the discretion of the investigators. The primary endpoint was virological response, defined as HIV-1 RNA of less than 50 copies per mL at week 48, in the per-protocol population, with a non-inferiority margin of 12%. We included patients who received at least one dose of the study drug in the safety analysis. This study is registered at ClinicalTrials.gov, number NCT01307488.
  
  
  RESULTS
  Between Sept 29, 2011, and May 2, 2013, we randomly assigned 286 patients (143 [50%] to each group). At week 48 in the per-protocol population, 112 (84%) of 133 patients had virological response in the dual-treatment group versus 105 (78%) of 135 in the triple-treatment group (difference 6% [95% CI -5 to 16%), showing non-inferiority at the prespecified level. 14 (5%) patients developed severe adverse events (dual treatment six [4%]; triple treatment eight [6%]), none of which we deemed related to the study drug. Grade 3-4 adverse events were similar between groups (dual treatment 77 [55%] of 140; triple treatment 78 [55%] of 141). Treatment discontinuations were less frequent in the dual-treatment group (three [2%]) than in the triple-treatment group (ten [7%]; p=0·047).
  
  
  CONCLUSIONS
  In our trial, dual treatment was effective, safe, and non-inferior to triple treatment in patients with an HIV-1 infection who are virologically suppressed who switch antiretroviral therapy because of toxic effects, intolerance, or simplification. This combination has the potential to suppress some of the long-term toxic effects associated with nucleos(t)ide reverse transcriptase inhibitors, preserve future treatment options, and reduce the cost of antiretroviral therapy.
  
  
  BACKGROUND
  Bristol Myers-Squibb and Fundación SEIMC-GESIDA.
authors.affiliation: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain. Electronic address: jperezm@salud.madrid.org.
authors.forename: José A
authors.initials: JA
authors.lastname: Perez-Molina
authors.affiliation: HIV Clinic, Hospital Universitario Doce de Octubre, Madrid, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Rubio
authors.affiliation: Infectious Diseases Unit, Hospital Universitario Reina Sofia, Instituto Maimónides de Investigación Biomédica de Córdoba, Córdoba, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Rivero
authors.affiliation: Infectious Diseases Unit, Hospital Universitario Virgen de las Nieves, Granada, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Pasquau
authors.affiliation: Infectious Diseases Unit, Complejo Hospitalario Universitario de Huelva, Huelva, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Suárez-Lozano
authors.affiliation: Infectious Diseases Unit, Hospital Son Espases, Mallorca, Spain.
authors.forename: Melcior
authors.initials: M
authors.lastname: Riera
authors.affiliation: Internal Medicine Department, Hospital Universitario La Paz, Instituto de Investigation Sanitaria del Hospital Universitario La Paz, Madrid, Spain.
authors.forename: Miriam
authors.initials: M
authors.lastname: Estébanez
authors.affiliation: Infectious Diseases Clinical Management Unit, Hospital Virgen de la Victoria, Málaga, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Santos
authors.affiliation: Infectious Diseases Unit, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Sanz-Moreno
authors.affiliation: Internal Medicine Department, Hospital Infanta Leonor, Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Troya
authors.affiliation: Infectious Diseases Unit, Internal Medicine Department, Complejo Hospitalario Universitario de Ferrol, Ferrol, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Mariño
authors.affiliation: Infectious Diseases Unit, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Antela
authors.forename: Jordi
authors.initials: J
authors.lastname: Navarro
authors.affiliation: Infectious Diseases Department, Hospital Universitari Vall d'Hebrón, Barcelona, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Navarro
authors.affiliation: Fundación Spanish Society of Infectious Diseases and Clinical Microbiology-Fundación SEIMC-GESIDA, Madrid, Spain.
authors.forename: Herminia
authors.initials: H
authors.lastname: Esteban
authors.affiliation: Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069446:Atazanavir Sulfate; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D057915:Drug Substitution; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000379:methods; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood*; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D019438:Ritonavir / Q000627:therapeutic use; D000068698:Tenofovir; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D003841:Deoxycytidine; D019259:Lamivudine; D015215:Zidovudine; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine; D019438:Ritonavir