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
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      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).
    

Intervention name(s): 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 type(s): Drug; Drug; Drug
Intervention description(s): 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
Other intervention name(s): Selzentry; Selzentry (maraviroc); Sustiva
Intervention MeSH terms: Efavirenz; Reverse Transcriptase Inhibitors; Raltegravir Potassium; Maraviroc
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HIV; HIV positive; Gastrointestinal Associated Lymphoid Tissue (GALT); GALT Immune Reconstruction; treatment naive