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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Stefano Rusconi, Ospedale L. Sacco - Polo Universitario
ClinicalTrials.gov Identifier:
NCT00884858
First received: April 20, 2009
Last updated: April 29, 2013
Last verified: April 2013
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Maraviroc
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: Use of Maraviroc (MVC) in Immunological Non-responder HIV-1-infected Patients.

Resource links provided by NLM:


Further study details as provided by Ospedale L. Sacco – Polo Universitario:

Primary Outcome Measures:
  • CD4 counts > 200/uL or recovery of CD4 > 25% in 2 consecutive time-points. [ Time Frame: 3 and 12 months ] [ Designated as safety issue: No ]

Enrollment: 100
Study Start Date: April 2009
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Maraviroc brand name in the EC is Celsentri.
No Intervention: 2
Subjects in this group will continue their current HAART without adding Maraviroc.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00884858

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

No publications provided by Ospedale L. Sacco – Polo Universitario

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Stefano Rusconi, Researcher/Aggregate professor in infectious diseases, Ospedale L. Sacco - Polo Universitario
ClinicalTrials.gov Identifier: NCT00884858     History of Changes
Other Study ID Numbers: HLS/MVC01/2008
Study First Received: April 20, 2009
Last Updated: April 29, 2013
Health Authority: Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by Ospedale L. Sacco – Polo Universitario:
HIV-1
CD4
INR
HIV-1 infection
extreme immunological compromission
treatment experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Infection
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases

ClinicalTrials.gov processed this record on October 20, 2014