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. Three 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.; 3) Sub-study C will evaluate the incidence of thromboembolic disease in the study patients along with baseline evaluation of possible bio-markers of pro-coagulant state.