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

Study Status: Terminated
Recruit Status: Unknown status
Study Type: Interventional

Official Title: CCR5 Antagonism to Decrease the Incidence of the Immune Reconstitution Inflammatory Syndrome in HIV-Infected Patients

Brief Summary: The purpose of this study is to determine if Maraviroc administration can decrease IRIS incidence in HIV infected patients initiating ARV therapy.

Detailed Summary: 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 b
Sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Current Primary Outcome: Time to occurrence of an IRIS event [ Time Frame: The initial 24 week period of observation ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Time to occurrence of a severe IRIS event [ Time Frame: The initial 24 week period of observation ]
  • Occurrence of either an IRIS event or death [ Time Frame: By 24 and 48 weeks ]
  • Proportion of subjects who develops an IRIS case [ Time Frame: By week 24 ]
  • Proportion of subjects who develop a severe IRIS case [ Time Frame: Week 24 ]
  • Proportion of subjects who develop a confirmed, non dermatologic IRIS case [ Time Frame: Week 24 ]
  • Proportion of subjects who develop an unmasking or paradoxical IRIS event [ Time Frame: Week 24 ]
  • Frequency of cardiovascular, cerebrovascular, non AIDS related neoplasia, cirrhosis, renal failure and death in both treatment arms [ Time Frame: During the study (from entry to week 60) ]
  • Frequency of AIDS defining events and AIDS related events in both arms of treatment [ Time Frame: From basline to study end ]
  • General survival [ Time Frame: At week 24 and 48 ]
  • Survival without IRIS [ Time Frame: At weeks 24 and 48 ]
  • Proportion of patients with VL<50 copies/mL [ Time Frame: At weeks 8, 24 and 48 ]
  • Changes form baseline in CD4+ cells count [ Time Frame: From baseline to weeks 12, 24 and 48 ]
  • Safety and tolerability of the treatment regimens [ Time Frame: Along the study ]
  • Incidence of HIV drug resistance [ Time Frame: Baseline to week 60 ]
  • Prevalence of CCR5 tropism [ Time Frame: Baseline ]
  • Prevalence of CCR5 HIV tropism [ Time Frame: At virological failure occurrence ]
  • Baseline predictors of IRIS [ Time Frame: Baseline ]
  • Genetic polymorphisms associated with the occurrence of IRIS [ Time Frame: Baseline ]
  • To evaluate the rol of biomarkers (CRP) in predicting or identifying IRIS and the effect of Maraviroc on this marker [ Time Frame: Baseline to IRIS event ]


Original Secondary Outcome:

  • Time to occurrence of a severe IRIS event [ Time Frame: The initial 24 week period of observation ]
  • Occurrence of either an IRIS event or death [ Time Frame: The initial 24 week period of observation ]
  • Occurrence of either an IRIS event or death [ Time Frame: First 48 weeks of study ]
  • Occurrence of virological failure [ Time Frame: At week 8 ]
  • Occurrence of virological failure [ Time Frame: At week 24 ]
  • Occurrence of virological failure [ Time Frame: At week 48 ]
  • Number of CD4+ lymphocytes [ Time Frame: At week 12 ]
  • Number of CD4+ lymphocytes [ Time Frame: At week 24 ]
  • Number of CD4+ lymphocytes [ Time Frame: At week 48 ]
  • Change in CD4+ counts [ Time Frame: From baseline to week 12 ]
  • Change in CD4+ counts [ Time Frame: From week 12 to week 48 ]
  • Occurrence of cardiovascular, cerebrovascular, non AIDS related neoplasia, cirrhosis and renal failure [ Time Frame: During the study (from entry to week 60) ]
  • Occurrence of any Maraviroc-related toxicity that warrants discontinuation of Maraviroc [ Time Frame: During the study (from entry to week 48) ]
  • Occurrence of any severe IRIS event [ Time Frame: During the study (from entry to week 48) ]


Information By: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Dates:
Date Received: October 1, 2009
Date Started: December 2009
Date Completion: April 2013
Last Updated: November 22, 2012
Last Verified: November 2012