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

NCT01173510 | Withdrawn Phase 4 DMC

• 1 other identifier: 10-184
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

HIV Infections; Acquired Immune Deficiency Syndrome

Keywords

HIV; AIDS; Atripla; Truvada; Raltegravir; Human Immunodeficiency Virus; Acquired Immune Deficiency Syndrome Virus

Outcome Measures

Primary Outcomes (2)

• 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.

  24 weeks

• 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.

  24 weeks

Secondary Outcomes (4)

• Efficacy in eradicating PBMC-associated early viral spliced mRNA

  24 weeks

• Efficacy in eradicating PBMC-associated viral genomic RNA

  24 weeks

• Efficacy in eradicating CD34+-cell-associated early viral spliced mRNA

  24 weeks

• Efficacy in eradicating CD34+-cell-associated viral genomic RNA

  24 weeks

Study Arms (2)

Raltegravir plus tenofovir/emtricitabine

EXPERIMENTAL

Drug: Raltegravir plus Truvada

Efavirenz/Emtricitabine/Tenofovir

ACTIVE COMPARATOR

Drug: Atripla

Interventions

Raltegravir plus Truvada DRUG

Raltegravir 400 mg twice daily plus tenofovir/emtricitabine (Truvada) one tablet once daily

Raltegravir plus tenofovir/emtricitabine

Atripla DRUG

Efavirenz/Emtricitabine/Tenofovir DF one tablet once daily

Efavirenz/Emtricitabine/Tenofovir

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Community Research Initiative of New England: lead
• Merck Sharp & Dohme LLC: collaborator

Related Links

• Community Research Initiative website

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Raltegravir Potassium; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Oxazines

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2010
• First Posted: August 2, 2010
• Study Start: August 23, 2010
• Primary Completion: October 19, 2012
• Study Completion: October 19, 2012
• Last Updated: June 14, 2017

Record last verified: 2017-06