Maraviroc in Immunological Non-Responder (INR) HIV-1-infected Subjects

April 29, 2013 updated by: Stefano Rusconi, ASST Fatebenefratelli Sacco

Use of Maraviroc (MVC) in Immunological Non-responder HIV-1-infected Patients.

Suboptimal improvement in cluster of differentiation 4 (CD4) cell count is not uncommon in HIV-1-infected patients with suppressed plasma HIV-Ribonucleic acid (RNA) levels, and a decrease in CD4 cell count in patients with suppressed or low level viremia has been observed.

Although the efficacy of current antiretroviral medications is well established, some antiviral combinations are very effective in suppressing HIV-1 load whereas do not exert any effect on immune reconstitution.

Both T-cell immune activation and fibrosis of peripheral lymphoid tissue could create an environment in which CD4 T cell count decrease in the setting of low or suppressed plasma viremia is likely to occur.

Another fascinating hypothesis, which has still to be elucidated, is that reconstitution of the depleted CD4 pool is blocked by an excess of glycoprotein 120 (gp120) HIV-1 protein. This extra-production could be counteracted by an inhibitor of the chemokine (C-C motif) receptor 5 (CCR5) co-receptor that represents one of the major docking tools of HIV-1.

With this in mind, the investigators would like to propose and design a pilot exploratory clinical trial involving a population of HIV-1-infected patients that rapidly reached a virologic suppression without a reconstitution of their immune system.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Objectives:

  • Evaluate the clinical efficacy of HAART intensification with MVC as treatment of HIV-1 infection in patients with a CD4 count ≤ 200 cells/uL and/or a recovery of CD4 cells < 25% compared to the HAART initiation and with a complete and stable virologic suppression after 12 months of HAART. Patients could also being included if their CD4 slope has been stable without any improvement, with an absolute value around 200 cells/uL.
  • Evaluate the effects of HAART intensification with MVC on the modification of immunologic and virologic parameters.
  • Evaluate the tolerability of HAART intensification with MVC and the appearance of drug-related side effects.

Design:

This will be a randomised, multicenter, study that will evaluate HAART intensification with MVC as treatment of HIV-1 infection in patients with a CD4 count ≤ 200 cells/uL and/or a recovery of CD4 cells < 25% compared to the HAART initiation and/or a stable CD4 slope without any improvement, with an absolute value around 200 cells/uL and with a complete and stable virologic suppression after 12 months of HAART.

Study Type

Interventional

Enrollment (Actual)

100

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
      • Napoli, Italy, 80131
        • Divisione Dipartimento Urgenze Infettivologiche ad Alta Complessità e correlate all'AIDS, Ospedale Cotugno
    • AN
      • Torrette di Ancona, AN, Italy, 60126
        • Servizio Regionale di Immunologia Clinica e Tipizzazione Tissutale, Azienda Ospedaliero-Universitaria
    • BA
      • Bari, BA, Italy, 70124
        • Clinica di Malattie Infettive, Policlinico, Universita' degli Studi
    • BS
      • Brescia, BS, Italy, 25125
        • Clinica di Malattie Infettive e Tropicali, Università degli Studi di Brescia, Spedali civili
    • FI
      • Antella, FI, Italy, 50011
        • Divisione di Malattie Infettive, Ospedale S. Maria Annunziata
    • GE
      • Genova, GE, Italy, 16132
        • Clinica di Malattie Infettive, Ospedale San Martino
    • MB
      • Monza, MB, Italy, 20052
        • Divisione di Malattie Infettive, Ospedale San Gerardo
    • MI
      • Milano, MI, Italy, 20124
        • Polo di Medicina Chirurgia e Odontoiatria, Polo Didattico S. Paolo
      • Milano, MI, Italy, 20132
        • U.O di Malattie Infettive, Fondazione San Raffaele del Monte Tabor
      • Milano, MI, Italy, 20157
        • Divisione Clinicizzata di Malatie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco"
      • Milano, MI, Italy, 20157
        • I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario Luigi Sacco
    • MO
      • Modena, MO, Italy, 41100
        • Clinica delle Malattie Infettive, Policlinico Universitario
    • PE
      • Pescara, PE, Italy, 65100
        • U.O. Malattie Infettive, Ospedale S. Spirito
    • PG
      • Perugia, PG, Italy, 06126
        • Clinica delle Malattie Infettive, Policlinico Monteluce
    • RM
      • Roma, RM, Italy, 00133
        • Clinica delle Malattie Infettive, Policlinico "Tor Vergata"
      • Roma, RM, Italy, 00149
        • III Divisione di Malattie Infettive, I.N.M.I Lazzaro Spallanzani
      • Roma, RM, Italy, 00149
        • IV Divisione di Malattie Infettive, INMI Lazzaro Spallanzani
      • Roma, RM, Italy, 00161
        • U.O. Malattie Infettive, Azienda Policlinico Umberto I
      • Roma, RM, Italy, 00168
        • Istituto Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore
    • TO
      • Torino, TO, Italy, 10149
        • Clinica delle Malattie Infettive ,Ospedale Amedeo di Savoia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • age > or = 18
  • HIV-Abs positivity detected by ELISA and confirmed by Western-Blot
  • CD4 lymphocytes < 200/uL and/or CD4 recovery < 25% after at least 12 months of stable HAART
  • HIV-RNA < 50 cp/mL during the last 12 months
  • negative pregnancy test at least 14 days prior to treatment
  • understanding and signing the informed consent

Exclusion Criteria:

  • allergy/intolerance to the study drug
  • less than 1 year from any treatment with immunomodulatory agents
  • current OIs or neoplasms
  • current CVD or EKG abnormalities
  • current respiratory tract diseases or COPD
  • treatment with steroids within 4 weeks from treatment beginning
  • suspect of autoimmune disorder or chronic inflammatory disease
  • active IVDUs or alcohol addicts
  • AST and ALT > 2.5 ULD
  • serum creatinine > 1.5 ULD
  • ANC < 1000/uL
  • hemoglobin < 10 g/dL
  • platelets < 75.000/uL
  • reticulocytes > 2%
  • Karnofsky score < 50

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Maraviroc
Subjects in this group will add Maraviroc to their current HAART.
Drug: Maraviroc
Maraviroc is administered BID according to the other drugs within HAART; dosage ranges from 150 mg to 600 mg bid.
Other Names:
  • Maraviroc brand name in the EC is Celsentri.
No Intervention: 2
Subjects in this group will continue their current HAART without adding Maraviroc.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
CD4 counts > 200/uL or recovery of CD4 > 25% in 2 consecutive time-points.
Time Frame: 3 and 12 months
3 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ASST Fatebenefratelli Sacco

Investigators

  • Principal Investigator: Stefano Rusconi, M.D., Universita' degli Studi di Milano, Italy

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

April 1, 2011

Study Completion (Actual)

April 1, 2011

Study Registration Dates

First Submitted

April 20, 2009

First Submitted That Met QC Criteria

April 20, 2009

First Posted (Estimate)

April 21, 2009

Study Record Updates

Last Update Posted (Estimate)

April 30, 2013

Last Update Submitted That Met QC Criteria

April 29, 2013

Last Verified

April 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HLS/MVC01/2008

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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