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

Phase 4

Completed

• Conditions: HIV Infections
• Interventions: Drug: Maraviroc

• Registration Number: NCT00884858
• Lead Sponsor: ASST Fatebenefratelli Sacco

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.

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 Timeline

• Study Start: 2009-04
• Study First Submitted: 2009-04-20
• Study First Submitted QC: 2009-04-20
• Study First Posted: 2009-04-21
• Primary Completion: 2011-04
• Study Completion: 2011-04
• Status Verified: 2013-04
• Last Update Submitted: 2013-04-29
• Last Update Posted: 2013-04-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 100

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
CD4 counts > 200/uL or recovery of CD4 > 25% in 2 consecutive time-points.	3 and 12 months

Trial Locations

Locations (20)

Servizio Regionale di Immunologia Clinica e Tipizzazione Tissutale, Azienda Ospedaliero-Universitaria; 🇮🇹 Torrette di Ancona, AN, Italy

Clinica di Malattie Infettive, Policlinico, Universita' degli Studi; 🇮🇹 Bari, BA, Italy

Clinica di Malattie Infettive e Tropicali, Università degli Studi di Brescia, Spedali civili; 🇮🇹 Brescia, BS, Italy

Divisione di Malattie Infettive, Ospedale S. Maria Annunziata; 🇮🇹 Antella, FI, Italy

Clinica di Malattie Infettive, Ospedale San Martino; 🇮🇹 Genova, GE, Italy

Divisione di Malattie Infettive, Ospedale San Gerardo; 🇮🇹 Monza, MB, Italy

Polo di Medicina Chirurgia e Odontoiatria, Polo Didattico S. Paolo; 🇮🇹 Milano, MI, Italy

U.O di Malattie Infettive, Fondazione San Raffaele del Monte Tabor; 🇮🇹 Milano, MI, Italy

Divisione Clinicizzata di Malatie Infettive, Azienda Ospedaliera-Polo Universitario "Luigi Sacco"; 🇮🇹 Milano, MI, Italy

I e II Divisione Malattie Infettive, Azienda Ospedaliera-Polo Universitario Luigi Sacco; 🇮🇹 Milano, MI, Italy

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