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A Pilot Study to Determine if Raltegravir Eradicates HIV From Peripheral Blood Mononuclear Cells

Primary Purpose

HIV Infections, Acquired Immune Deficiency Syndrome

Status
Withdrawn
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Raltegravir plus Truvada
Atripla
Sponsored by
Community Research Initiative of New England
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring HIV, AIDS, Atripla, Truvada, Raltegravir, Human Immunodeficiency Virus, Acquired Immune Deficiency Syndrome Virus

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female subjects age 18 or older with HIV-1 infection
  • CD4 cell counts greater than 200 cells/mm at screening
  • Plasma HIV RNA > 1000 copies/mL
  • Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to eight weeks after the last dose of study drug. Women of childbearing potential includes any woman who has experienced menarche and who has not undergone successful surgical sterilization or who is not post-menopausal.

Exclusion Criteria:

  • Previous exposure to antiretroviral medications used in the treatment of HIV-1 infection
  • Evidence of genotypic or phenotypic resistance to most of the medications that will be used in the study (tenofovir, emtricitabine, and efavirenz) on a resistance assay obtained through the patient's primary care physicians as a standard of care test
  • Women with a positive pregnancy test, who are pregnant, or who are breast feeding
  • Sexually active non-sterilized men not using effective birth control if they have female partners who are of child-bearing potential
  • Women of child-bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to eight weeks after the last dose of study drug
  • Presence of any currently active AIDS-defining category C conditions according to the CDC Classification System for HIV Infection with the exception of stable cutaneous Kaposi's sarcoma
  • Any active, clinically significant disease that in the opinion of the Principal Investigator may compromise the subject's safety during the trial
  • Grade 3 or 4 Laboratory abnormalities as defined by a standardized grading scheme based on the DAIDS table - ACTG Toxicity Grading Scale elevations (except pre-existing diabetes mellitus with asymptomatic, non-fasting glucose grade 3 elevations, asymptomatic ≥ grade 3 fasting triglyceride or cholesterol elevations, and subjects with elevated indirect bilirubin)
  • Active substance abuse or significant psychiatric illness that in the opinion of the Principal Investigator may interfere with study compliance
  • Prisoners or subjects who are involuntarily incarcerated
  • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness
  • Known hypersensitivity to G-CSF

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Raltegravir plus tenofovir/emtricitabine

    Efavirenz/Emtricitabine/Tenofovir

    Arm Description

    Outcomes

    Primary Outcome Measures

    Efficacy in eradicated HIV-1 integrated DNA from PBMCs
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating HIV-1 integrated DNA from peripheral blood mononuclear cells (PBMCs) in healthy HIV-infected participants who are naïve to antiretroviral therapy.
    Efficacy in eradicating HIV-1 integrated DNA from CD34+ cells
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating HIV-1 integrated DNA from CD34+ cells mobilized from the bone marrow in healthy HIV-infected participants who are naïve to antiretroviral therapy.

    Secondary Outcome Measures

    Efficacy in eradicating PBMC-associated early viral spliced mRNA
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating PBMC-associated early viral spliced mRNA (tat, rev, and nef) in healthy HIV-infected participants who are naïve to antiretroviral therapy.
    Efficacy in eradicating PBMC-associated viral genomic RNA
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating PBMC-associated viral genomic RNA in healthy HIV-infected participants who are naïve to antiretroviral therapy.
    Efficacy in eradicating CD34+-cell-associated early viral spliced mRNA
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating CD34+-cell-associated early viral spliced mRNA (tat, rev, and nef) in healthy HIV-infected participants who are naïve to antiretroviral therapy.
    Efficacy in eradicating CD34+-cell-associated viral genomic RNA
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating CD34+cell-associated viral genomic RNA in healthy HIV-infected participants who are naïve to antiretroviral therapy.

    Full Information

    First Posted
    July 29, 2010
    Last Updated
    June 13, 2017
    Sponsor
    Community Research Initiative of New England
    Collaborators
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01173510
    Brief Title
    A Pilot Study to Determine if Raltegravir Eradicates HIV From Peripheral Blood Mononuclear Cells
    Official Title
    A Pilot Study to Determine if Raltegravir Eradicates HIV From Peripheral Blood Mononuclear Cells
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    June 2017
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    This study was not feasible due to facility budget and contractual issues.
    Study Start Date
    August 23, 2010 (Anticipated)
    Primary Completion Date
    October 19, 2012 (Actual)
    Study Completion Date
    October 19, 2012 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Community Research Initiative of New England
    Collaborators
    Merck Sharp & Dohme LLC

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    Human Immunodeficiency Virus (HIV) infection is permanently established by integrating a deoxyribonucleic acid (DNA) copy into the human chromosome, a step also necessary to complete the Human Immunodeficiency Virus (HIV)replication cycle. Standard treatment of HIV infection suppresses Human Immunodeficiency Virus (HIV)replication and has not been able to eliminate Human Immunodeficiency Virus (HIV)from an infected person because of the integrated Human Immunodeficiency Virus (HIV). Raltegravir (RAL), the first approved antiretroviral (ARV) in a new class called integrase inhibitors, works by preventing integration of Human Immunodeficiency Virus (HIV). For participants with Human Immunodeficiency Virus (HIV)who have never taken antiretroviral medications, this research study will test whether Raltegravir (RAL), a recommended first-line ARV, can eliminate Human Immunodeficiency Virus (HIV)from key immune system cells.
    Detailed Description
    This is a phase IV study comparing RAL to EFV ability to clear the HIV from mononuclear cells. Participants will be randomized 2:1 to either RAL plus co-formulated FTC/TDF or EFV/FTC/TDF (Atripla). The study will last a minimum of 24 weeks. Participants will come in three days before the weeks 4 and 24 visits to receive a subcutaneous injection of G-CSF, an FDA-approved medication that mobilizes certain cells. A minimum of 5 visits will be required after baseline for blood draws, safety monitoring, or G-CSF injections.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    HIV Infections, Acquired Immune Deficiency Syndrome
    Keywords
    HIV, AIDS, Atripla, Truvada, Raltegravir, Human Immunodeficiency Virus, Acquired Immune Deficiency Syndrome Virus

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Raltegravir plus tenofovir/emtricitabine
    Arm Type
    Experimental
    Arm Title
    Efavirenz/Emtricitabine/Tenofovir
    Arm Type
    Active Comparator
    Intervention Type
    Drug
    Intervention Name(s)
    Raltegravir plus Truvada
    Intervention Description
    Raltegravir 400 mg twice daily plus tenofovir/emtricitabine (Truvada) one tablet once daily
    Intervention Type
    Drug
    Intervention Name(s)
    Atripla
    Intervention Description
    Efavirenz/Emtricitabine/Tenofovir DF one tablet once daily
    Primary Outcome Measure Information:
    Title
    Efficacy in eradicated HIV-1 integrated DNA from PBMCs
    Description
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating HIV-1 integrated DNA from peripheral blood mononuclear cells (PBMCs) in healthy HIV-infected participants who are naïve to antiretroviral therapy.
    Time Frame
    24 weeks
    Title
    Efficacy in eradicating HIV-1 integrated DNA from CD34+ cells
    Description
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating HIV-1 integrated DNA from CD34+ cells mobilized from the bone marrow in healthy HIV-infected participants who are naïve to antiretroviral therapy.
    Time Frame
    24 weeks
    Secondary Outcome Measure Information:
    Title
    Efficacy in eradicating PBMC-associated early viral spliced mRNA
    Description
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating PBMC-associated early viral spliced mRNA (tat, rev, and nef) in healthy HIV-infected participants who are naïve to antiretroviral therapy.
    Time Frame
    24 weeks
    Title
    Efficacy in eradicating PBMC-associated viral genomic RNA
    Description
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating PBMC-associated viral genomic RNA in healthy HIV-infected participants who are naïve to antiretroviral therapy.
    Time Frame
    24 weeks
    Title
    Efficacy in eradicating CD34+-cell-associated early viral spliced mRNA
    Description
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating CD34+-cell-associated early viral spliced mRNA (tat, rev, and nef) in healthy HIV-infected participants who are naïve to antiretroviral therapy.
    Time Frame
    24 weeks
    Title
    Efficacy in eradicating CD34+-cell-associated viral genomic RNA
    Description
    To study the efficacy of Raltegravir plus Tenofovir DF/Emtricitabine versus Efavirenz/Emtricitabine/Tenofovir DF in eradicating CD34+cell-associated viral genomic RNA in healthy HIV-infected participants who are naïve to antiretroviral therapy.
    Time Frame
    24 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Male or female subjects age 18 or older with HIV-1 infection CD4 cell counts greater than 200 cells/mm at screening Plasma HIV RNA > 1000 copies/mL Women of childbearing potential must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to eight weeks after the last dose of study drug. Women of childbearing potential includes any woman who has experienced menarche and who has not undergone successful surgical sterilization or who is not post-menopausal. Exclusion Criteria: Previous exposure to antiretroviral medications used in the treatment of HIV-1 infection Evidence of genotypic or phenotypic resistance to most of the medications that will be used in the study (tenofovir, emtricitabine, and efavirenz) on a resistance assay obtained through the patient's primary care physicians as a standard of care test Women with a positive pregnancy test, who are pregnant, or who are breast feeding Sexually active non-sterilized men not using effective birth control if they have female partners who are of child-bearing potential Women of child-bearing potential who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to eight weeks after the last dose of study drug Presence of any currently active AIDS-defining category C conditions according to the CDC Classification System for HIV Infection with the exception of stable cutaneous Kaposi's sarcoma Any active, clinically significant disease that in the opinion of the Principal Investigator may compromise the subject's safety during the trial Grade 3 or 4 Laboratory abnormalities as defined by a standardized grading scheme based on the DAIDS table - ACTG Toxicity Grading Scale elevations (except pre-existing diabetes mellitus with asymptomatic, non-fasting glucose grade 3 elevations, asymptomatic ≥ grade 3 fasting triglyceride or cholesterol elevations, and subjects with elevated indirect bilirubin) Active substance abuse or significant psychiatric illness that in the opinion of the Principal Investigator may interfere with study compliance Prisoners or subjects who are involuntarily incarcerated Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness Known hypersensitivity to G-CSF
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Clyde S Crumpacker, MD
    Organizational Affiliation
    Beth Israel Deaconess Medical Center - Division of Infectious Disease
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Calvin J Cohen, MD
    Organizational Affiliation
    Community Research Initiative of New England
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Links:
    URL
    http://www.crine.org
    Description
    Community Research Initiative website

    Learn more about this trial

    A Pilot Study to Determine if Raltegravir Eradicates HIV From Peripheral Blood Mononuclear Cells

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