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

This study has been completed.
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
ClinicalTrials.gov Identifier:
NCT00735072
First received: August 12, 2008
Last updated: June 13, 2012
Last verified: June 2012
Results First Received: June 5, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: HIV Infection
Interventions: Drug: Placebo
Drug: Maraviroc

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Subjects were recruited from the HIV clinics at San Francisco General Hospital, Stanford University, Case Western Reserve University, and Rush University/CORE Center between September, 2008, and December, 2009.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
All 45 enrolled patients were assigned to study intervention. We over-enrolled by 3 subjects given 2 premature treatment discontinuations and one subject with unavailable baseline peripheral blood mononuclear cell (PBMC) samples available for analysis.

Reporting Groups
  Description
Maraviroc Maraviroc (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).
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).

Participant Flow:   Overall Study
    Maraviroc     Placebo  
STARTED     23     22  
COMPLETED     22     21  
NOT COMPLETED     1     1  
interrupted study med during ARV change                 1                 0  
Subject interrupted ARVs (non-adherence)                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Maraviroc Maraviroc (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).
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).
Total Total of all reporting groups

Baseline Measures
    Maraviroc     Placebo     Total  
Number of Participants  
[units: participants]
  23     22     45  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     23     21     44  
>=65 years     0     1     1  
Age  
[units: years]
Mean ± Standard Deviation
  50  ± 8     50  ± 10     50  ± 9  
Gender  
[units: participants]
     
Female     0     2     2  
Male     23     20     43  
Region of Enrollment  
[units: participants]
     
United States     23     22     45  



  Outcome Measures

1.  Primary:   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 ]
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Measure Type Primary
Measure Title 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)
Measure Description No text entered.
Time Frame Week 24  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Maraviroc Maraviroc (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).
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).

Measured Values
    Maraviroc     Placebo  
Number of Participants Analyzed  
[units: participants]
  23     22  
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)  
[units: %CD38+ HLA-DR+ CD8+ T cells]
Median ( Inter-Quartile Range )
  2.2  
  ( -0.6 to 4.1 )  
  -0.7  
  ( -3.5 to 0.6 )  


Statistical Analysis 1 for 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)
Groups [1] All groups
Method [2] Wilcoxon (Mann-Whitney)
P Value [3] 0.014
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Null hypothesis: there will be no difference in the week 24 change in %activated CD8+ T cells between arms. Assuming a standard deviation as high as 3.5% and a Type I error of 5%, with 21 subjects in each treatment arm we would have 80% statistical power to detect a mean 3 percentage-point difference in the percent of activated CD8+ T cells between the active drug and placebo groups.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.



2.  Secondary:   Change in CD4+ T Cell Count   [ Time Frame: Week 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

3.  Secondary:   Change in Ultra-sensitive Plasma HIV RNA Level (Single Copy/ml Assay)   [ Time Frame: Week 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

4.  Secondary:   Change in Brachial Artery Flow-mediated Dilatation (UCSF Site Only)   [ Time Frame: Week 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No

5.  Secondary:   Change in Gut-associated Lymphoid Tissue HIV RNA Level (UCSF Site Only)   [ Time Frame: Week 24 ]
Results not yet posted.   Anticipated Posting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Peter W. Hunt, MD
Organization: UCaliforniaSF
phone: (415) 476-4082 ext 345
e-mail: phunt@php.ucsf.edu


No publications provided by University of California, San Francisco

Publications automatically indexed to this study:

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00735072     History of Changes
Other Study ID Numbers: GA9001DE
Study First Received: August 12, 2008
Results First Received: June 5, 2011
Last Updated: June 13, 2012
Health Authority: United States: Institutional Review Board