Maraviroc Immune Recovery Study (MIRS)
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).
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Maraviroc Immune Recovery Study, A Multicenter, Randomized, Placebo-controlled, Exploratory Mechanistic Study Into the Role of Maraviroc on Immune Recovery|
- 30% increase in CD4+ cell count after 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||February 2009|
|Study Completion Date:||August 2012|
|Primary Completion Date:||December 2011 (Final data collection date for primary outcome measure)|
|Active Comparator: Maraviroc||
maraviroc dose dependent on co-medication
Placebo Comparator: Placebo
|Onze Lieve Vrouwe Gasthuis|
|Amsterdam, Netherlands, 1091 AC|
|Academisch Medisch Centrum (AMC)|
|Amsterdam, Netherlands, 1105AZ|
|Leids Universitair Medisch Centrum (LUMC)|
|Rotterdam, Netherlands, 3015GJ|
|Sint Elisabeth Ziekenhuis|
|Ùniversity Medical Center Utrecht|
|Utrecht, Netherlands, 3584CX|
|Principal Investigator:||Andy IM Hoepelman, MD, PhD||UMC Utrecht|