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Withdrawn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
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
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
NCT ID
NCT01173510
First Posted
July 29, 2010
Last Updated
June 13, 2017
Sponsor
Community Research Initiative of New England
Collaborators
Merck Sharp & Dohme LLC
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
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A Pilot Study to Determine if Raltegravir Eradicates HIV From Peripheral Blood Mononuclear Cells
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