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

NCT ID: NCT00884858

Last Updated: 2013-04-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE4

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-04-30

Study Completion Date

2011-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infections

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Maraviroc

Subjects in this group will add Maraviroc to their current HAART.

Group Type EXPERIMENTAL

Maraviroc

Intervention Type DRUG

Maraviroc is administered BID according to the other drugs within HAART; dosage ranges from 150 mg to 600 mg bid.

2

Subjects in this group will continue their current HAART without adding Maraviroc.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Maraviroc

Maraviroc is administered BID according to the other drugs within HAART; dosage ranges from 150 mg to 600 mg bid.

Intervention Type DRUG

Other Intervention Names

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Maraviroc brand name in the EC is Celsentri.

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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ASST Fatebenefratelli Sacco

OTHER

Sponsor Role lead

Responsible Party

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Stefano Rusconi

Researcher/Aggregate professor in infectious diseases

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Stefano Rusconi, M.D.

Role: PRINCIPAL_INVESTIGATOR

Universita' degli Studi di Milano, Italy

Locations

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Servizio Regionale di Immunologia Clinica e Tipizzazione Tissutale, Azienda Ospedaliero-Universitaria

Torrette Di Ancona, AN, Italy

Site Status

Clinica di Malattie Infettive, Policlinico, Universita' degli Studi

Bari, BA, Italy

Site Status

Clinica di Malattie Infettive e Tropicali, Università degli Studi di Brescia, Spedali civili

Brescia, BS, Italy

Site Status

Divisione di Malattie Infettive, Ospedale S. Maria Annunziata

Antella, FI, Italy

Site Status

Clinica di Malattie Infettive, Ospedale San Martino

Genova, GE, Italy

Site Status

Divisione di Malattie Infettive, Ospedale San Gerardo

Monza, MB, Italy

Site Status

Polo di Medicina Chirurgia e Odontoiatria, Polo Didattico S. Paolo

Milan, MI, Italy

Site Status

U.O di Malattie Infettive, Fondazione San Raffaele del Monte Tabor

Milan, MI, Italy

Site Status

Divisione Clinicizzata di Malatie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco"

Milan, MI, Italy

Site Status

I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario Luigi Sacco

Milan, MI, Italy

Site Status

Clinica delle Malattie Infettive, Policlinico Universitario

Modena, MO, Italy

Site Status

Divisione Dipartimento Urgenze Infettivologiche ad Alta Complessità e correlate all'AIDS, Ospedale Cotugno

Napoli, Napoli, Italy

Site Status

U.O. Malattie Infettive, Ospedale S. Spirito

Pescara, PE, Italy

Site Status

Clinica delle Malattie Infettive, Policlinico Monteluce

Perugia, PG, Italy

Site Status

Clinica delle Malattie Infettive, Policlinico "Tor Vergata"

Roma, RM, Italy

Site Status

III Divisione di Malattie Infettive, I.N.M.I Lazzaro Spallanzani

Roma, RM, Italy

Site Status

IV Divisione di Malattie Infettive, INMI Lazzaro Spallanzani

Roma, RM, Italy

Site Status

U.O. Malattie Infettive, Azienda Policlinico Umberto I

Roma, RM, Italy

Site Status

Istituto Clinica delle Malattie Infettive, Università Cattolica del Sacro Cuore

Roma, RM, Italy

Site Status

Clinica delle Malattie Infettive ,Ospedale Amedeo di Savoia

Torino, TO, Italy

Site Status

Countries

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Italy

References

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Rusconi S, Vitiello P, Adorni F, Colella E, Foca 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.

Reference Type DERIVED
PMID: 24244635 (View on PubMed)

Other Identifiers

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HLS/MVC01/2008

Identifier Type: -

Identifier Source: org_study_id