Maraviroc (CCR5) Antagonism to Decrease the Incidence of the Immune Reconstitution Inflammatory Syndrome in HIV-Infected Patients

This is a randomized, double blind, placebo-controlled, multicenter study testing the
utility of a CCR5 antagonist (Maraviroc) as an adjuvant to a standard HAART regimen to
decrease the incidence of Immune Reconstitution Inflammatory Syndrome (IRIS) in HIV-infected
patients naïve to antiretroviral treatment. The study duration will be 60 weeks, 276
subjects (138 per arm) will be recruited. The population included will be HIV-infected
patients starting antiretroviral (ARV) therapy at the participating centers in Mexico and
South Africa with a CD4 T cell count <100 cells/ul. Subjects will be randomized to receive
either Maraviroc (study drug) or placebo in addition to background ARV therapy. The
background antiretroviral regimen for all subjects will be: Efavirenz 600mg QD + Tenofovir
300 mg / Emtricitabine 200 mg QD; subjects will be randomized to one of the following arms:
Arm A: background ARV + maraviroc 600mg po BID; Arm B: background ARV + placebo po BID.
Patients will be followed for 48 weeks. The primary endpoint will be the occurrence of a
defined IRIS event by week 24 of follow up. The success of the ARV therapy will also be
evaluated by virologic and immunologic response at 24 and 48 weeks. Two immunology
sub-studies are planned: 1) Sub-study A will be conformed by a subgroup of 40 subjects (20
from Mexico and 20 from South Africa), additional blood sampling will be performed to
evaluate expression of immune activation markers; movement of central memory T cells into
cell cycle and frequencies of expandable pathogen-reactive CD4+ and CD8+ T cells in
circulation; 2) Sub-study B will be conformed by another subgroup of 60 subjects (all from
South Africa), additional blood sampling will be performed to evaluate monocyte and CD4 T
cell gene expression as related to activation-induced apoptosis and cytokine secretion.