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Atazanavir/r + Lamivudine Dual Therapy (ATLAS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01599364
Recruitment Status : Completed
First Posted : May 16, 2012
Last Update Posted : July 24, 2019
Information provided by (Responsible Party):
Simona Di Giambenedetto, Catholic University of the Sacred Heart

Brief Summary:
The purpose of this study is to evaluate the virological efficacy of maintenance therapy with atazanavir with ritonavir combined with lamivudine in treatment experienced HIV positive patients with full and stable virological suppression.

Condition or disease Intervention/treatment Phase
Human Immunodeficiency Virus Drug: Atazanavir, ritonavir, lamivudine Phase 4

Detailed Description:

The introduction of combined antiretroviral therapy (cART) dramatically improved the prognosis of HIV infection [1]; nowadays, virological suppression (viral load < 50 copies/mL) can be obtained in the vast majority of patients receiving cART. Nevertheless, antiretroviral drugs have short- and long-term side effects mainly regarding mitochondrial toxicity, impaired lipid and glucose metabolism, impairment of renal function and bone density and may contribute to increase the patients' cardiovascular risk.

Current treatment guidelines recommend three drug regimens with a "backbone" of 2 nucleos(t)ide reverse transcriptase inhibitors (N(t)RTIs) and a "third drug" to be chosen among non-nucleoside reverse transcriptase inhibitors (NNRTIs) and ritonavir-boosted protease inhibitors (PIr). Regimens containing less than three antiretroviral drugs are currently not recommended based on the high risk of virological failure and selection of drug resistance mutations (DRM) with previous experience of NRTI-only based approaches with the exception of boosted PIs monotherapy which is optional in patients with intolerance to NRTIs or requiring treatment simplification provided that they never experienced virological failures or admitted in exceptional circumstances.

Nevertheless, the investigation of possible new treatment paradigms remains attractive due to the high potency and low risk of selection of drug resistance mutations with PIr based therapies and the established long term toxicity of even newer and currently preferred N(t)RTIs, in particular the renal and bone toxicity of tenofovir and the debated potential association with increased cardiovascular risk of abacavir, which has been described in some cohort studies. Studies evaluating N(t)RTI-sparing treatment strategies are thus increasing in order to try to respond to the unmet medical needs of HIV-infected patients with metabolic complications and increasing risk of cardiovascular or renal diseases.

These studies will need to investigate the safety and efficacy of these alternative strategies, also evaluating their possible effects on renal function, bone mass density and risk of premature osteoporosis.

Atazanavir with ritonavir is a generally well tolerated lipid-friendly protease inhibitor with mild effects on lipid metabolism even when combined with low-dose ritonavir and is the only drug who achieved a non-significant difference in virological efficacy compared to efavirenz; like all other PIr-based regimens, failure of an atazanavir/ritonavir containing cART seems to protect against the development of drug resistance mutations to both the PI and the backbone. Lamivudine is a well tolerated NRTI which showed no significant toxicity in the short and long term and, together with its analog emtricitabine, is now a preferred option in most of the major international treatment guidelines; it has a good CNS penetration score and its only signature resistance mutation (M184V) deeply impairs the viral fitness and does not compromise the future treatment options.

The combination of these two drugs could therefore be an appealing possibility for treatment switch in stably virologically suppressed treatment-experienced patients with toxicity-related issues. The results of a previously planned 24 weeks interim analysis of a monocentric 48 weeks Italian pilot study evaluating this strategy in 40 patients has recently been presented at IAS conference in Vienna and showed no virologic failures without any "blip" and good tolerability with a significant improvement of renal function as measured by MDRD. These data look very promising and allow us to be confident in designing a randomized study in order to confirm these findings.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 266 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety and Efficacy of Switching a Stable Combined Antiretroviral Therapeutic Regimen to Atazanavir With Ritonavir Plus Lamivudine in Treatment Experienced HIV Positive Patients With Full and Stable Virological Suppression
Study Start Date : April 2014
Actual Primary Completion Date : April 2016
Actual Study Completion Date : February 23, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Switch
Switch to Atazanavir 300 mg with ritonavir 100 mg plus lamivudine 300 mg
Drug: Atazanavir, ritonavir, lamivudine
Lamivudine 300 mg 1 pill once-a-day, atazanavir 300 mg 1 pill with ritonavir 100 mg 1 pill once-a-day, taken together orally with a light meal
Other Name: Lamivudine (Epivir, GSK), Atazanavir (Reyataz, BMS), Ritonavir (Norvir, Abbott)

No Intervention: continue
Continue Atazanavir 300 mg with ritonavir 100 mg with the same NRTI backbone

Primary Outcome Measures :
  1. Proportion of patients with viral load < 50 copies/mL [ Time Frame: at week 48 ]
    Proportion of patients with viral load < 50 copies/mL at week 48 at the intention-to-treat with switch = failure analysis

Secondary Outcome Measures :
  1. Efficacy and the safety of atazanavir with ritonavir combined with lamivudine in treatment experienced HIV positive patients with full and stable virological suppression [ Time Frame: 48 and 96 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria

  • HIV positive patients 18 years of age or older who signed an informed consent form
  • Already on cART, without any treatment interruption.
  • Treated with a cART regimen containing atazanavir boosted with ritonavir since at least 3 months
  • With full virological suppression (VL<50 copies/mL) for a minimum of six months and in at least in two consecutive determination 3 months +/-2 weeks apart from each other
  • With CD4 cell count >200 since at least 6 months and without opportunistic infections or other AIDS-related events since at least one year before screening

Exclusion Criteria:

  • Previous virological failure on a lamivudine- or PI-containing regimen or previous exposure to lamivudine-containing suboptimal antiretroviral regimens
  • Patients with at least a single viral load blip over 200 copies/mL
  • Patients with M184V or major atazanavir resistance mutation at previous genotypic resistance test (historical genotype)
  • Pregnancy or lactation, planned pregnancy in the short-term
  • Patients with HBsAg positive chronic HBV infection
  • Patients who experienced major toxicities related to any of the study drugs in the past
  • Patients with grade 4 laboratory abnormalities at baseline (excluding lipid profile and plasma bilirubin concentration).
  • Patients with non-AIDS related illnesses which could, in the Clinician's judgement, jeopardize the patient's compliance to the study procedures (i.e. Child-Pugh B or higher liver cirrhosis, active cancers on treatment…).
  • Patients treated with proton-pump inhibitors or other concomitant medication with potential for interactions reducing exposure to atazanavir

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01599364

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Sponsors and Collaborators
Catholic University of the Sacred Heart
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Study Chair: Mauro MM Moroni, MD Università di Milano Direttore clinica Malattie infettive
Study Chair: Pierluigi PZ Zoccolotti, MD Università di Roma La Sapienza Dipartimento di Psicologia
Study Chair: Stafano SV Vella, MD Dipartimento del farmaco all'Istituto Superiore della Sanità
Principal Investigator: Roberto RC Cauda, MD Università Cattolica del S. Cuore Policlinico Universitario A. Gemelli
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Simona Di Giambenedetto, MD, Catholic University of the Sacred Heart Identifier: NCT01599364    
Other Study ID Numbers: ATLAS 2
2011-001060-21 ( EudraCT Number )
First Posted: May 16, 2012    Key Record Dates
Last Update Posted: July 24, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Simona Di Giambenedetto, Catholic University of the Sacred Heart:
HIV infection
virological suppression
Combined antiretroviral therapy
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Blood-Borne Infections
Communicable Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Slow Virus Diseases
Atazanavir Sulfate
HIV Protease Inhibitors
Viral Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP3A Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors