A Pilot Project of Virologic, Pharmacologic and Immunologic Correlates of Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution Following Maraviroc Therapy
Condition: HIV Infections
MeSH terms: HIV Infections
Intervention: maraviroc in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor); maraviroc plus raltegravir in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor); efavirenz [or other NNRTI (non-nucleoside reverse transcriptase inhibitor)]
Intervention description: maraviroc 300mg 1 tablet taken twice a day without regard to food taken in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician; maraviroc 300mg 1 tablet taken twice a day without regard to food PLUS raltegravir 400mg 1 tablet taken twice a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician; efavirenz 600mg 1 capsule is taken once a day without regard to food in combination with 2 NRTIs (dual nucleoside reverse transcriptase inhibitor) pre-determined with primary care physician
Intervention MeSH terms: Efavirenz; Reverse Transcriptase Inhibitors; Raltegravir Potassium; Maraviroc
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 44.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: HIV; HIV positive; Gastrointestinal Associated Lymphoid Tissue (GALT); GALT Immune Reconstruction; treatment naive

Summary:

      This research study is being done to find out how the immune system in the small intestines
      improves after taking antiretroviral (anti-HIV) medications. Biopsies (small snips of tissue)
      will be taken from the part of the intestines just below the stomach, and will be studied in
      the laboratory. The main purpose of this study is to measure the increase in the numbers of
      immune cells in the intestines to see if this number is related to the amount of medication
      that reaches the intestinal tissue, and the amount of virus that is still hiding there.

      Subjects are either normal control subjects without HIV or, are HIV positive and are about to
      start HIV medications. As part of this study, HIV positive patients will be randomized to
      receive one of three possible combinations of medications.

        1. maraviroc (Selzentry) in combination with 2 NRTIs (dual nucleoside reverse transcriptase
           inhibitor) or

        2. maraviroc PLUS raltegravir in combination with 2 NRTIs (dual nucleoside reverse
           transcriptase inhibitor) or

        3. efavirenz (Sustiva) in combination with 2 NRTIs (dual nucleoside reverse transcriptase
           inhibitor)

      Both Maraviroc and Raltegravir each represent new classes of medications in the way that they
      interfere with HIV making copies of itself. Maraviroc attaches to the surface of the T-cell
      that the virus uses to get into the cell and is therefore known as an entry inhibitor.
      Raltegravir blocks the virus from inserting itself into the DNA of the infected cell's
      nucleus and is therefore known as an Integrase Inhibitor. We hope to learn more about how
      antiretroviral drugs affect T cells and how immune function restores itself when HIV
      infection is treated.
    

Eligibility criteria:

        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