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:
1. In the treatment group subjects will start with a registered antiretroviral agent
(maraviroc).
2. During the treatment year patients will perform several study visits, probably three
more compared with regular visits on the outpatient clinic.
3. Each visit, blood will be drawn by venepuncture for immunologic and virologic
investigations (see flow chart).
Phase:
Phase 4
Details
Lead Sponsor:
S.F.L. van Lelyveld
Collaborators:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) Erasmus Medical Center Leiden University Medical Center Onze Lieve Vrouwe Gasthuis Pfizer Rijnstate Hospital Slotervaart Hospital