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

Study Description

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Brief Summary:

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 or disease	Intervention/treatment	Phase
HIV Infections	Drug: Maraviroc	Phase 4

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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	100 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Use of Maraviroc (MVC) in Immunological Non-responder HIV-1-infected Patients.
Study Start Date :	April 2009
Actual Primary Completion Date :	April 2011
Actual Study Completion Date :	April 2011

Arms and Interventions

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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 Name: Maraviroc brand name in the EC is Celsentri.
No Intervention: 2; Subjects in this group will continue their current HAART without adding Maraviroc.

Outcome Measures

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Primary Outcome Measures :

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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
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

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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
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
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
Milano, MI, Italy, 20157
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
Clinica delle Malattie Infettive, Policlinico "Tor Vergata"
Roma, RM, Italy, 00133
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, 00149
U.O. Malattie Infettive, Azienda Policlinico Umberto I
Roma, RM, Italy, 00161
Istituto Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore
Roma, RM, Italy, 00168
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

ASST Fatebenefratelli Sacco

Investigators

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

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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
First Posted:	April 21, 2009
Last Update Posted:	April 30, 2013
Last Verified:	April 2013

Keywords provided by Stefano Rusconi, Ospedale L. Sacco - Polo Universitario:

HIV-1; CD4; INR	HIV-1 infection; extreme immunological compromission; treatment experienced

Additional relevant MeSH terms:

HIV Infections; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes	Immune System Diseases; Maraviroc; CCR5 Receptor Antagonists; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents