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

This study has been withdrawn prior to enrollment.
(This study was not feasible due to facility budget and contractual issues.)
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Cal Cohen, Community Research Initiative of New England
ClinicalTrials.gov Identifier:
NCT01173510
First received: July 29, 2010
Last updated: December 11, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Acquired Immune Deficiency Syndrome
Drug: Raltegravir plus Truvada
Drug: Atripla
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study to Determine if Raltegravir Eradicates HIV From Peripheral Blood Mononuclear Cells

Resource links provided by NLM:


Further study details as provided by Community Research Initiative of New England:

Primary Outcome Measures:
  • Efficacy in eradicated HIV-1 integrated DNA from PBMCs [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 0
Arms Assigned Interventions
Experimental: Raltegravir plus tenofovir/emtricitabine Drug: Raltegravir plus Truvada
Raltegravir 400 mg twice daily plus tenofovir/emtricitabine (Truvada) one tablet once daily
Active Comparator: Efavirenz/Emtricitabine/Tenofovir Drug: Atripla
Efavirenz/Emtricitabine/Tenofovir DF one tablet once daily

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01173510

Sponsors and Collaborators
Community Research Initiative of New England
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Clyde S Crumpacker, MD Beth Israel Deaconess Medical Center - Division of Infectious Disease
Principal Investigator: Calvin J Cohen, MD Community Research Initiative of New England
  More Information

Additional Information:
No publications provided

Responsible Party: Cal Cohen, Director of Research, Community Research Initiative of New England
ClinicalTrials.gov Identifier: NCT01173510     History of Changes
Other Study ID Numbers: 10-184
Study First Received: July 29, 2010
Last Updated: December 11, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Community Research Initiative of New England:
HIV
AIDS
Atripla
Truvada
Raltegravir
Human Immunodeficiency Virus
Acquired Immune Deficiency Syndrome Virus

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Efavirenz, emtricitabine, tenofovir disoproxil fumarate drug combination
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 31, 2014