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Maraviroc as an Immunomodulatory Drug for Antiretroviral-treated HIV Infected Patients Exhibiting Immunologic Failure

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ClinicalTrials.gov Identifier: NCT00735072
Recruitment Status : Completed
First Posted : August 14, 2008
Results First Posted : July 18, 2012
Last Update Posted : July 18, 2012
Sponsor:
Collaborators:
Pfizer
amfAR, The Foundation for AIDS Research
Stanford University
Case Western Reserve University
Rush University
Information provided by (Responsible Party):
University of California, San Francisco

Study Description
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Brief Summary:

Many people with HIV fail to regain normal CD4 counts despite effectively suppressing HIV replication with medications. Blocking the "co-receptor" for HIV might decrease inflammation of the immune system, potentially providing an immune benefit. The goal of the current trial is to determine whether adding maraviroc, a new CCR5 "co-receptor" blocker, decreases inflammation, providing an immune benefit for patients with low CD4 counts despite undetectable viral loads on HIV medications.

In this study, HIV-infected patients who are receiving antiretroviral therapy for HIV will receive either maraviroc or a placebo (sugar pill) each day for 24 weeks. After 24 weeks, the study medication will be stopped and all subjects will be followed for 12 more weeks. Blood tests measuring the extent of inflammation, low-level viremia, and immune function will be measured throughout the trial and compared between treatment arms.


Condition or disease Intervention/treatment Phase
HIV Infection Drug: Placebo Drug: Maraviroc Phase 4

Detailed Description:
Our primary hypothesis is that CCR5 inhibitors may have protective immunomodulatory effects independent of their impact on HIV replication. Specifically, we predict that maraviroc will reduce the persistent T cell activation that prevents normal immune reconstitution during HAART-mediated viral suppression. This hypothesis will be tested in the context of a placebo controlled pilot study assessing the impact of maraviroc in antiretroviral-treated patients with a CD4+ T cell count less than 350 cells/mm3. In order to address the immunologic activity of this drug independent of plasma HIV RNA levels, we will study individuals who have undetectable viral loads (< 75 copies RNA/mL). Subjects will be randomized to maraviroc for 24 weeks or matching placebo for 24 weeks, followed by a 12 week washout period. We will use as our primary endpoint the proportion of CD8+ T cells that co-expresses CD38 and HLA-DR, as these outcomes have been well validated in prior studies. The primary outcome will be change in the percentage of activated CD8+ T cells at week 24. Change in CD4+ T cell counts, HIV RNA levels (using ultra-sensitive techniques), and other more experimental immunologic measurements will be assessed as secondary outcomes.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Maraviroc as an Immunomodulatory Drug for Antiretroviral-treated HIV Infected Patients Exhibiting Immunologic Failure
Study Start Date : September 2008
Actual Primary Completion Date : April 2010
Actual Study Completion Date : July 2010

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS
Drug Information available for: Maraviroc
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Experimental: Maraviroc
Maraviroc (dose based on current medications in regimen: 150mg orally (PO) twice daily (BID) for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens).
 Drug: Maraviroc
Dose based on current medications in regimen: 150mg orally (PO) twice daily (BID) for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens.
Other Name: Selzentry
Placebo Comparator: Placebo
Placebo (dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens).
 Drug: Placebo
Dose based on current medications in regimen: 150mg PO BID for those on a protease inhibitor-based regimen other than Tipranavir; 600mg PO BID for efavirenz-containing regimens; or 300 mg PO BID for all other regimens.
Other Name: Placebo for Maraviroc


Outcome Measures
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Primary Outcome Measures :
  1. Week 24 Change in Percentage of CD8+ T Cells That Co-express CD38 and HLA DR (Week 24 %CD38+HLA-DR+ CD8+ T Cells Minus Baseline %CD38+HLA-DR+ CD8+ T Cells) [ Time Frame: Week 24 ]

Secondary Outcome Measures :
  1. Change in CD4+ T Cell Count [ Time Frame: Week 24 ]
  2. Change in Ultra-sensitive Plasma HIV RNA Level (Single Copy/ml Assay) [ Time Frame: Week 24 ]
  3. Change in Brachial Artery Flow-mediated Dilatation (UCSF Site Only) [ Time Frame: Week 24 ]
  4. Change in Gut-associated Lymphoid Tissue HIV RNA Level (UCSF Site Only) [ Time Frame: Week 24 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HIV-1 infection, as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
  2. Stable antiretroviral therapy for at least 12 months
  3. Screening CD4+ T cell count below 350 cells/mm3
  4. All available CD4+ T cell counts in the last year and at screening < 350 cells/mm3
  5. Screening plasma HIV RNA levels below level of detection (< 50 copies RNA/mL using Roche Amplicor or < 75 copies/mL using Bayer bDNA)
  6. All available plasma HIV RNA levels within past year below the level of detection. Isolated values that are detectable but < 500 copies will be allowed as long as the plasma HIV RNA levels before and after this time point are undetectable.
  7. > 90% adherence to therapy within the preceding 30 days, as determined by self-report.
  8. Both male and female subjects are eligible. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.
  9. Ability and willingness of subject or legal guardian/representative to provide informed consent

Exclusion Criteria:

  1. Increase in CD4 count of > 100 cells/mm3 in past year.
  2. Patients who are intending to modify antiretroviral therapy in the next 24 weeks for any reason.
  3. Serious illness requiring hospitalization or parental antibiotics within preceding 3 months.
  4. Concurrent treatment with immunomodulatory drugs, or exposure to any immunomodulatory drug in past 16 weeks.
  5. HBVsAg+ or active hepatitis C or hepatitis B which will require treatment in the subsequent 24 weeks.
  6. Prior exposure to CCR5 inhibitors
  7. Screening absolute neutrophil count <1,000 cells/mm3, platelet count <50,000 cells/mm3, hemoglobin < 8mg/dL, estimated creatinine clearance <40 mL/minute.
  8. Pregnant or breastfeeding women
  9. Use of both Tenofovir and Didanosine in current antiretroviral therapy regimen.
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00735072


Locations
United States, California
University of California San Francisco - San Francisco General Hospital
San Francisco, California, United States, 94110
Stanford University
Stanford, California, United States, 94305
United States, Illinois
Rush University - Stroger Hospital of Cook County
Chicago, Illinois, United States, 60612
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
University of California, San Francisco
Pfizer
amfAR, The Foundation for AIDS Research
Stanford University
Case Western Reserve University
Rush University
Investigators
Principal Investigator: Peter W Hunt, MD University of California, San Francisco
Principal Investigator: Steven G Deeks, MD University of California, San Francisco
Principal Investigator: Nancy Shulman, MD Stanford University
Principal Investigator: Robert Shafer, MD Stanford University
Principal Investigator: Michael Lederman, MD Case Western Reserve University
Principal Investigator: Toyin Adeyemi, MD Rush University
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00735072     History of Changes
Other Study ID Numbers: GA9001DE
First Posted: August 14, 2008    Key Record Dates
Results First Posted: July 18, 2012
Last Update Posted: July 18, 2012
Last Verified: June 2012

Keywords provided by University of California, San Francisco:
HIV infection
T cell activation
Antiretroviral Therapy
CCR5
Maraviroc

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Efavirenz
Maraviroc
Tipranavir
Protease Inhibitors
HIV Protease Inhibitors
Reverse Transcriptase Inhibitors
 Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Cytochrome P-450 CYP2C9 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 CYP2B6 Inducers
Cytochrome P-450 Enzyme Inducers
Cytochrome P-450 CYP3A Inducers
CCR5 Receptor Antagonists
Anti-HIV Agents