Maraviroc Immune Recovery Study

Study Overview
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Brief Summary
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Rationale: Improving cellular immunity by means of increasing CD4 cells is one of the goals of antiretroviral therapy in HIV, which is achieved by means of virological suppression. A certain group of patients, the so called immunologic non responders, fail to reach an acceptable CD4 cell increase despite an adequate virologic response on antiretroviral treatment. Recently a new antiretroviral agent, maraviroc (Celsentry®), is registered for the treatment of patients infected with CCR5 tropic HIV-1 virus. However, data is available suggesting that treatment with maraviroc leads to immune recovery (increase in CD4 cells) in patients who are infected with dual/mixed tropic HIV-1 virus, in the absence of a virologic response. This suggests an alternative mechanism for immune recovery, which could be especially beneficial for this group of patients. Hypothesis: Maraviroc, by a yet unknown mechanism, stimulates immune recovery by increasing CD4+ cell count. Objective: The primary objective is to confirm the hypothesis that maraviroc stimulates immune recovery; the secondary objective is to explore, by virologic and immunologic investigations, the underlying mechanisms of this hypothesis. Study design: multicentre, randomized, placebo-controlled, double blind, exploratory mechanistic study. Study population: HIV-1 infected patients 18 years or older, who meet the inclusion criteria. Intervention: One group receives maraviroc (dose dependent on co-medication), the other group placebo. Main study parameters/endpoints: A 30% increase in CD4 cell rise in the treatment group (compared with placebo). Nature and extent of the burden and risks associated with participation, benefit and group relatedness: In the treatment group subjects will start with a registered antiretroviral agent (maraviroc). During the treatment year patients will perform several study visits, probably three more compared with regular visits on the outpatient clinic. Each visit, blood will be drawn by venepuncture for immunologic and virologic investigations (see flow chart).

Official Title
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Maraviroc Immune Recovery Study, A Multicenter, Randomized, Placebo-controlled, Exploratory Mechanistic Study Into the Role of Maraviroc on Immune Recovery

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: maraviroc
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 years or older HAART with a maximal treatment interruption of two weeks viral suppression (< 50 copies/ml) for 6 months And either: CD4+ count < 200 cells/microliter after minimal one year of treatment with HAART (study group one) OR a CD4+ cell count between 200 and 350 cells/microliter after minimal two years of treatment with HAART (study group two) Exclusion Criteria: HAART consisting of a combination of tenofovir and didanosine Active infection for which antimicrobial treatment Acute hepatitis B or C Chronic hepatitis B or C for which treatment with (peg)interferon and/or ribavirin (Note: patients with untreated chronic hepatitis B or C can be included) Immunosuppressive medication Radiotherapy or chemotherapy in the past 2 years Pregnancy or breastfeeding an infant Subjects with known hypersensitivity to maraviroc or to peanuts, or any of its excipients or dyes as follows: Excipients from tablet: microcrystalline cellulose, dibasic calcium phosphate (anhydrous), sodium starch glycolate, magnesium stearate. Film-coat: [Opadry II Blue (85G20583) contains FD&C blue #2 aluminium lake, soya lecithin, polyethylene glycol (macrogol 3350), polyvinyl alcohol, talc and titanium dioxide.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Maraviroc<br> | Drug: maraviroc<br>* maraviroc dose dependent on co-medication<br>* Other names: Celsentry;|
| Placebo Comparator: Placebo<br>Placebo drug | Drug: Placebo<br>* Placebo drug<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 30% increase in CD4+ cell count after 48 weeks |  | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HAART, CD4 cell, Immunologic non-responders, Immunology, treatment experienced, HIV-1