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 (ATLAS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2012 by Catholic University of the Sacred Heart
Sponsor:
Information provided by (Responsible Party):
Simona Di Giambenedetto, Catholic University of the Sacred Heart
ClinicalTrials.gov Identifier:
NCT01599364
First received: May 14, 2012
Last updated: May 15, 2012
Last verified: May 2012
  Purpose

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 Intervention Phase
Human Immunodeficiency Virus
Drug: Atazanavir, ritonavir, lamivudine
Drug: Atazanavir, Ritonavir, 2 NRTIs
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Catholic University of the Sacred Heart:

Primary Outcome Measures:
  • Proportion of patients with viral load < 50 copies/mL [ Time Frame: at week 48 ] [ Designated as safety issue: No ]
    Proportion of patients with viral load < 50 copies/mL at week 48 at the intention-to-treat with switch = failure analysis


Estimated Enrollment: 266
Study Start Date: August 2011
Estimated Study Completion Date: November 2014
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 and 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
Drug: Atazanavir, Ritonavir, 2 NRTIs
Atazanavir 300 mg 1 pill with ritonavir 100 mg 1 pill once-a-day, taken together orally with a light meal with the 2 NRTIs previously taken by the patient
Other Name: Atazanavir (Reyataz, BMS), ritonavir (Norvir, Abbott), 2 NRTIs

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV positive patients 18 years of age or older who signed an informed consent form
  • On cART since no more than 3 years, 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)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01599364

Contacts
Contact: Niccoletta NC Ciccarelli, PsyD +0390630155366 nicoletta.ciccarelli@rm.unicatt.it

Locations
Italy
Ospedale S. M. Annunziata - U.O. Malattie Infettive Not yet recruiting
Bagno a Ripoli, Firenze, Italy, 50011
Contact: Elisa EM Mariabelli    +390556936512    laboratorio.malattie_infettive@asf.toscana.it   
Sub-Investigator: Massimo MD Di Pietro, MD         
P.O. "S. Caterina Novella" - UOC di Malattie Infettive Not yet recruiting
Galatina, Lecce, Italy, 73013
Contact: Mariangela MT Tana, MD    +390836529681    mariangelatana@virgilio.it   
Sub-Investigator: Pierfrancesco PG Grima, MD         
Azienda Ospedaliero Universitaria - Ospedali Riuniti di Ancona Struttura Organizzativa Dipartimentale (S.O.D) Clinica di Malattie infettive Not yet recruiting
Ancona, Italy, 60126
Contact: Francesco FB Barchiesi, MD    +390715963715    f.barchiesi@univpm.it   
Sub-Investigator: Andrea AG Giacometti, MD         
Azienda Ospedaliera Spedali Civili - Istituto di Malattie Infettive e Tropicali Not yet recruiting
Brescia, Italy, 25123
Contact: Silvia SA Amadasi, MD    +39030399.6507    silvia.amadasi@live.it   
Sub-Investigator: Carlo CT Torti, MD         
A.O. Universitaria -Cagliari - Centro di Immunologia Not yet recruiting
Cagliari, Italy, 09042
Contact: Amarilli AB Boccone, MD    +3907051096373    amarilli@boccone.it   
Sub-Investigator: Paolo Emilio PM Manconi, MD         
Azienda Ospedaliera di Rilievo Nazionale di alta specializzazione Garibaldi di Catania - Istituto Malattie infettive Not yet recruiting
Catania, Italy, 95122
Contact: Maurizio MB Benedetto, MD    +390957598650    bmcelesia@tin.it   
Sub-Investigator: Maria Teresa MM Mugnini, MD         
Azienda Ospedaliera Universitaria San Martino - Clinica Malattie Infettive Not yet recruiting
Genova, Italy, 16132
Contact: Antonio AD Di Biagio, MD    +390105555142    antonio.dibiagio@hsanmartino.it   
Sub-Investigator: Claudio CV Viscoli, MD         
A.O. Ospedale Niguarda Cà Granda - Malattie Infettive Not yet recruiting
Milano, Italy, 20126
Contact: Maria Cristina Moioli, MD    +390264442806    mariacristina.moioli@ospedaleniguarda.it   
Sub-Investigator: Massimo MP Puoti, MD         
Ospedale Luigi Sacco di Milano Azienda ospedaliera e Polo Universitario - Dip. di Scienze Cliniche L. Sacco / Sez. Malattie Infettive Not yet recruiting
Milano, Italy, 20157
Contact: Stefano SR Rusconi, MD    +390239042668    stefano.rusconi@unimi.it   
Sub-Investigator: Massimo MG Galli, MD         
Ospedale Luigi Sacco di Milano - Malattie infettive I Divisione Not yet recruiting
Milano, Italy, 20157
Contact: Amedeo AC Capetti, MD    +390239042345    capetti.amedeo@hsacco.it   
Sub-Investigator: Giuliano GR Rizzardini, MD         
A.O. Universitaria Policlinico Paolo Giaccone di Palermo - Malattie Infettive Not yet recruiting
Palermo, Italy, 9127
Contact: MAURIZIO MM MINEO, MD    +390916554055    maumineo@libero.it   
Sub-Investigator: Maurizio MM Mineo, MD         
Università Cattolica del S. Cuore Policlinico Universitario A. Gemelli - Istituto di Clinica delle Malattie Infettive Recruiting
Roma, Italy, 00168
Contact: Nicoletta Ciccarelli, Psyd    +390630155366    nicoletta.ciccarelli@rm.unicatt.it   
Principal Investigator: Roberto RC Cauda, MD         
IRCCS Istituto Dermatologico S. Gallicano (IFO) - UOC Dermatologia Infettiva Recruiting
Roma, Italy, 00144
Contact: Massimo MG Giuliani, MD    +390652662806    giuliani@ifo.it   
Sub-Investigator: Guido GP Palamara, MD         
I.N.M.I. L. Spallanzani I.R.C.C.S. - .O.C. Malattie Infettive e Tropicali IV Divisione Not yet recruiting
Roma, Italy, 00149
Contact: Rita RB Bellagamba, MD    +390655170361    rita.bellagamba@inmi.it   
Sub-Investigator: Andrea AA Antinori, MD         
Università' degli studi di Roma La Sapienza - Dipartimento di Malattie Infettive e Tropicali Not yet recruiting
Roma, Italy, 00161
Contact: Gabriella GD D'Ettorre, MD    +390649970801    gabriella.dettorre@uniroma1.it   
Sub-Investigator: Vincenzo VV Vullo, MD         
I.N.M.I. L. Spallanzani I.R.C.C.S. - U.O.C. Infezioni Sistemiche e dell'Immunodepresso II Divisione Not yet recruiting
Roma, Italy, 00149
Contact: Evangelo EB Boumis, MD    +390655170357    boumis@inmi.it   
Sub-Investigator: Nicola NP Petrosillo, MD         
Università degli studi di Sassari - Reparto Malattie Infettive Not yet recruiting
Sassari, Italy, 07100
Contact: Giordano GM Madeddu, MD    +39079228202    giordano.madeddu@uniss.it   
Sub-Investigator: Maria Stella MM Mura, MD         
Ospedale Amedeo di Savoia - Divisione A Malattie Infettive Not yet recruiting
Torino, Italy, 10149
Contact: Giancarlo GO Orofino, MD    +3901143933819    orofino@aslto2.it   
Sub-Investigator: Pietro PC Caramello, MD         
Azienda ULSS 9 Treviso Ospedale S. Maria di Ca'Foncello - U.O. Malattie infettive Not yet recruiting
Treviso, Italy, 31100
Contact: Maria Cristina MR Rossi, MD    +390422322065    crossi@ulss.tv.it   
Sub-Investigator: Pier Giorgio PS Scotton, MD         
Azienda Ospedaliera Universitaria Integrata di Verona - U.O.C. Malattie infettive Not yet recruiting
Verona, Italy, 37134
Contact: Fabiana FC Corsini, MD    +390458128256    fabianacorsini@libero.it   
Sub-Investigator: Ercole EC Concia, MD         
Sponsors and Collaborators
Catholic University of the Sacred Heart
Investigators
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
  More Information

Additional Information:
No publications provided

Responsible Party: Simona Di Giambenedetto, MD, Catholic University of the Sacred Heart
ClinicalTrials.gov Identifier: NCT01599364     History of Changes
Other Study ID Numbers: ATLAS 2, 2011-001060-21
Study First Received: May 14, 2012
Last Updated: May 15, 2012
Health Authority: Italy: The Italian Medicines Agency

Keywords provided by Catholic University of the Sacred Heart:
HIV infection
Atazanavir
Lamivudine
Ritonavir
virological suppression
non-inferiority
Combined antiretroviral therapy

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
HIV Seropositivity
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immune System Diseases
Lamivudine
Ritonavir
Atazanavir
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014