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

April 20, 2009
April 29, 2013
April 2009
April 2011   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00884858 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Maraviroc in Immunological Non-Responder (INR) HIV-1-infected Subjects
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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
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.
  • Experimental: Maraviroc
    Subjects in this group will add Maraviroc to their current HAART.
    Intervention: Drug: Maraviroc
  • No Intervention: 2
    Subjects in this group will continue their current HAART without adding Maraviroc.
Rusconi S, Vitiello P, Adorni F, Colella E, Focà E, Capetti A, Meraviglia P, Abeli C, Bonora S, D'Annunzio M, Di Biagio A, Di Pietro M, Butini L, Orofino G, Colafigli M, d'Ettorre G, Francisci D, Parruti G, Soria A, Buonomini AR, Tommasi C, Mosti S, Bai F, Di Nardo Stuppino S, Morosi M, Montano M, Tau P, Merlini E, Marchetti G. Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial. PLoS One. 2013 Nov 14;8(11):e80157. doi: 10.1371/journal.pone.0080157. eCollection 2013.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
100
April 2011
April 2011   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Italy
 
NCT00884858
HLS/MVC01/2008
No
Stefano Rusconi, Ospedale L. Sacco - Polo Universitario
Ospedale L. Sacco – Polo Universitario
Not Provided
Principal Investigator: Stefano Rusconi, M.D. Universita' degli Studi di Milano, Italy
Ospedale L. Sacco – Polo Universitario
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP