Simplification to Atazanavir/Ritonavir + Lamivudine as Maintenance Therapy (SALT)

Efficacy of Simplification to Atazanavir/Ritonavir + Lamivudine as Maintenance Therapy in Patients With Viral Suppression. Randomized, Open-label 96 Weeks Non-inferiority Trial

A switch to a regimen consisting of ATV/RTV 300/100 mg QD + 3TC 300 mg QD in HIV-1 infected subjects in their first antiretroviral regimen and who are virologically suppressed on a regimen which consists of 2 NRTIs + any 3rd agent, is non-inferior to continue or switch to ATV/RTV 300/100 mg QD + 2 optimized NRTIs for maintenance of virological suppression.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: Ritonavir boosted Atazanavir + Lamivudine; Drug: Ritonavir boosted Atazanavir + 2 NRTIs

Detailed Description

Clinical Trial, phase IV, randomized, open label, multicenter with approved drugs in their use conditions.

A switch to a regimen consisting of ATV/RTV 300/100 mg QD + 3TC 300 mg QD in HIV-1 infected subjects in their first antiretroviral regimen and who are virologically suppressed on a regimen which consists of 2 NRTIs + any 3rd agent, is non-inferior to continue or switch to ATV/RTV 300/100 mg QD + 2 optimized NRTIs for maintenance of virological suppression.

• Study Type: Interventional
• Enrollment (Actual): 286
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain
    • Hospital General de Alicante
  • Asturias, Spain
    • H. Universitario Central de Asturias
  • Barcelona, Spain
    • Hospital Vall d'Hebron
  • Barcelona, Spain
    • Hospital Santa Creu i Sant Pau
  • Córdoba, Spain
    • Hospital Reina Sofia
  • Granada, Spain
    • Hospital Virgen de las Nieves
  • Granada, Spain
    • Hospital Clínico San Cecilio
  • Huelva, Spain
    • H. Juan Ramón Jimenez
  • La Coruña, Spain
    • Hospital Juan Canalejo
  • Madrid, Spain
    • Hospital Ramon y Cajal
  • Madrid, Spain
    • H. Clínico San Carlos
  • Madrid, Spain
    • Hospital Gregorio Marañón
  • Madrid, Spain
    • Hospital Doce de Octubre
  • Madrid, Spain
    • Hospital La Paz
  • Madrid, Spain
    • H. Universitario Infanta Leonor
  • Mallorca, Spain
    • H. Universitario Son Espases
  • Mataró, Spain
    • Hospital de Mataró
  • Málaga, Spain
    • Hospital Virgen de la Victoria
  • Pamplona, Spain
    • Hospital de Navarra
  • San Sebastián, Spain
    • Hospital Donostia
  • Santander, Spain
    • Hospital Marques de Valdecilla
  • Tarragona, Spain
    • Hospital de Santa Tecla
  • Valencia, Spain
    • Hospital La Fe
  • Alicante
    • Elche, Alicante, Spain
      • Hospital de Elche
    • Villajoyosa, Alicante, Spain
      • Hospital Marina Baixa
  • Barcelona
    • Badalona, Barcelona, Spain
      • H. Germans Trias i Pujol
    • Granollers, Barcelona, Spain
      • Hospital General de Granollers
  • Cádiz
    • Jerez de la Frontera, Cádiz, Spain
      • Hospital de Jerez
  • La Coruña
    • Santiago de Compostela, La Coruña, Spain
      • Complexo Hospitalario Universitario De Santiago
  • La Rioja
    • Logroño, La Rioja, Spain
      • H. San Pedro
  • Madrid
    • Alcalá de Henares, Madrid, Spain
      • Hospital Principe de Asturias
    • Leganés, Madrid, Spain
      • Hospital Severo Ochoa
  • Málaga
    • Marbella, Málaga, Spain
      • Hospital Costa del Sol
  • Pontevedra
    • El Ferrol, Pontevedra, Spain
      • Hospital Arquitecto Marcide
    • Vigo, Pontevedra, Spain
      • Hospital Xeral Cíes
  • Vizcaya
    • Basurto, Vizcaya, Spain
      • Hospital de Basurto

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signature of informed consent
• At least 18 years old
• Patients on their 1st ARV treatment consisting on 2 NRTIs + 1 third agent for at least 1 year
• Undetectable viral load for at least 6 months prior to inclusion in the study (VL<50 c/mL in 2 determinations 6 months apart; blips are not allowed).
• Requirement of ARV treatment change due to toxicity, intolerance or simplification.
• Clinically stable.

Exclusion Criteria:

• Pregnant women or women who plan to get pregnant during the study.
• Breast feeding
• History of change of any ARV treatment component for any reason 4 months prior to the inclusion in the trial
• History of ARV treatment change due to virological failure
• History of confirmed virological failure defined as one single VL >400 c/mL or at least 2 VL between 50 and 400 c/mL one year after an indetectable VL was achieved.
• Absence of HIV genotype prior to ARV treatment initiation.
• Resistance mutation to any of the study drugs (ATV, RTV, 3TC)
• HBV infection.
• History of toxicity or intolerance to ATV, RTV or 3TC.
• Gilbert's syndrome.
• Use of contraindicated drugs.
• Lab abnormalities grade 4.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATV/r+3TC; Subjects will receive ATV/RTV 300/100 mg QD + 2 optimized NRTIs for the first 4 weeks and then they will receive ATV/RTV 300/100 mg QD (once daily) and 3TC 300 mg QD for another 92 weeks. Treatment should be taken orally with a light meal at the same time each day.	Drug: Ritonavir boosted Atazanavir + Lamivudine; ATV/RTV 300/100 mg QD + 2 optimized NRTIs for the first 4 weeks and then they will receive ATV/RTV 300/100 mg QD (once daily) and 3TC 300 mg QD for another 92 weeks. Treatment should be taken orally with a light meal at the same time each day.
Active Comparator: ATV/r+2 NRTIs; Subjects will receive ATV/RTV 300/100 mg QD + 2 optimized NRTIs for 96 weeks. Treatment should be taken orally with a light meal at the same time each day.	Drug: Ritonavir boosted Atazanavir + 2 NRTIs; ATV/RTV 300/100 mg QD + 2 optimized NRTIs for 96 weeks. Treatment should be taken orally with a light meal at the same time each day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the non-inferiority of maintenance therapy with ATV/RTV + 3TC vs ATV/RTV + 2 optimized NRTIs	Non-inferiority will be considered when the difference in proportion of efficacy between experimental arm (ATV/RTV + 3TC) vs. control arm (ATV/RTV + 2 optimized NRTIs) arm is less or equal to -0.12% after 48 weeks of treatment	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the non-inferiority of maintenance therapy with ATV/RTV + 3TC vs ATV/RTV + 2 optimized NRTIs	Non-inferiority will be considered when the difference in proportion of efficacy between experimental arm (ATV/RTV + 3TC) vs. control arm (ATV/RTV + 2 optimized NRTIs) arm is less or equal to -0.12% after 24 weeks of treatment	week 24
To assess the non-inferiority of maintenance therapy with ATV/RTV + 3TC vs ATV/RTV + 2 optimized NRTIs	Non-inferiority will be considered when the difference in proportion of efficacy between experimental arm (ATV/RTV + 3TC) vs. control arm (ATV/RTV + 2 optimized NRTIs) arm is less or equal to -0.12% after 96 weeks of treatment	week 96
To assess safety after 24 weeks fo treatment	Frequency of adverse events, SAEs, AEs leading to discontinuations, death and laboratory abnormalities. Describe renal function, plasma Vitamin D and bone density changes (DEXA) from baseline and particularly in those patients receiving TDF at screening.	Week 24
To assess safety after 48 weeks fo treatment	Frequency of adverse events, SAEs, AEs leading to discontinuations, death and laboratory abnormalities. Describe renal function, plasma Vitamin D and bone density changes (DEXA) from baseline and particularly in those patients receiving TDF at screening.	Week 48
To assess safety after 96 weeks fo treatment	Frequency of adverse events, SAEs, AEs leading to discontinuations, death and laboratory abnormalities. Describe renal function, plasma Vitamin D and bone density changes (DEXA) from baseline and particularly in those patients receiving TDF at screening.	Week 96
To assess the incidence of resistance, and characterization of this resistance following a virological rebound	Genotypic antiretroviral resistance profiles of subjects experiencing virologic failure (genotype) Plasma samples at Baseline and at each visit will be stored for additional resistance studies (i.e. cDNA)	Week 96
To assess neurocognitive function evolution	Nerocognitive function evolution measured through a battery of standardized tests from baseline to week 48	Week 48
To assess neurocognitive function evolution	Nerocognitive function evolution measured through a battery of standardized tests from baseline to week 96	Week 96

Collaborators and Investigators

• Sponsor: Fundacion SEIMC-GESIDA
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: José A Pérez-Molina, MD, Hospital Universitario Ramon Y Cajal

Publications and helpful links

General Publications

• Perez-Molina JA, Rubio R, Rivero A, Pasquau J, Suarez-Lozano I, Riera M, Estebanez M, Santos J, Sanz-Moreno J, Troya J, Marino A, Antela A, Navarro J, Esteban H, Moreno S; GESIDA 7011 Study Group. 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. Lancet Infect Dis. 2015 Jul;15(7):775-84. doi: 10.1016/S1473-3099(15)00097-3. Epub 2015 Jun 7. Erratum In: Lancet Infect Dis. 2015 Sep;15(9):998.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): April 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: March 1, 2011
• First Submitted That Met QC Criteria: March 2, 2011
• First Posted (Estimate): March 3, 2011

Study Record Updates

• Last Update Posted (Estimate): May 12, 2015
• Last Update Submitted That Met QC Criteria: May 8, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: HIV; AIDS; Atazanavir; Simplification
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ritonavir; Lamivudine; Atazanavir Sulfate
• Other Study ID Numbers: GESIDA 7011; 2011-001107-12 (EudraCT Number)