A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Maraviroc Therapy

Despite improved survival, durable virologic suppression, and increases in peripheral CD4+ T-cell counts in patients receiving potent antiretroviral therapy (ART), immune reconstitution remains incomplete as measured by a number of additional surrogate markers. Perhaps critically important among areas of apparent incomplete immune recovery is the gastrointestinal-associated lymphoid tissue (GALT), where CD4+ T-cells repopulate very slowly if at all. Several new classes of antiretrovirals (ART) have recently been approved by the FDA that offer potential advantages in terms of immune reconstitution and/or the kinetics viral suppression over traditionally available treatment regimens. Maraviroc is a new ART agent from a novel class of HIV inhibitors, entry inhibitors, that results in rapid suppression of HIV and recovery of peripheral CD4+ T-cells. This project proposes to examine whether volunteers receiving maraviroc recover GALT immune cells more completely that those taking comparator ART. Raltegravir is an integrase inhibitor that blocks incorporation of the proviral HIV DNA into the host chromosomes leading to more rapid declines in plasma HIV load than has previously been observed. This project proposes to examine whether volunteers receiving maraviroc or maraviroc plus raltegravir recover GALT immune cells more completely that those taking comparator ART. An additional attraction of the use of maraviroc and raltegravir together is that they may provide a potent combination that is also lipid neutral and thereby constitute a 'Heart friendly HAART' (Highly Active Antiretroviral Therapy).

Inclusion criteria

• Males and Females ages 18 years to 60 years inclusive
• HIV positive (no anticipated antiretroviral therapy adjustments/changes)
• CD4 count greater than or equal to 50 cells/ml within 30 days of screening
• CCR5 tropism by Trofile ES(TM)
• Can be on secondary prophylaxis with a history of AIDS defining illness
• All females of child-bearing potential must agree to use barrier methods to prevent pregnancy or be abstinent from sexual activity while on study.
• willing to sign consent form
• HIV Negative individuals will also be recruited for this study as a Control Group

Exclusion criteria

• allergy to peanuts or soya (maraviroc contains soya lecithin)
• abnormal coagulation parameters (PT greater than or equal to 1.2 ULN)
• thrombocytopenia (platelet count less than 50,000 within 6 weeks)
• known GI pathology
• contra-indications to upper endoscopy or conscious sedation
• anemia greater than grade 1
• any active acute opportunistic infection (OI) or therapy for acute OI within 30 days of entry into study
• positive pregnancy test
• aspirin, ibuprofen, warfarin, or other agents that interfere with the coagulation cascade taken within 1 week of endoscopy