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

Study Overview
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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.

Official Title
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Use of Maraviroc (MVC) in Immunological Non-responder HIV-1-infected Patients.

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Maraviroc


Participation Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maraviroc<br>Subjects in this group will add Maraviroc to their current HAART. | Drug: Maraviroc<br>* Maraviroc is administered BID according to the other drugs within HAART; dosage ranges from 150 mg to 600 mg bid.<br>* Other names: Maraviroc brand name in the EC is Celsentri.;|
| No Intervention: 2<br>Subjects in this group will continue their current HAART without adding Maraviroc. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CD4 counts > 200/uL or recovery of CD4 > 25% in 2 consecutive time-points. |  | 3 and 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, CD4, INR, HIV-1 infection, extreme immunological compromission, treatment experienced