Adding Maraviroc to Antiretroviral Therapy for Suboptimal CD4 T-Cell Recovery Despite Sustained Virologic Suppression

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
AIDS Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00709111
First received: July 1, 2008
Last updated: January 23, 2012
Last verified: January 2012
Results First Received: July 26, 2011  
Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: HIV Infections
Intervention: 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
Recruited at 29 AIDS Clinical Trials Units in the United States between January 14, 2009 and May 4, 2009

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
34 enrolled

Reporting Groups
  Description
Maraviroc Maraviroc (MVC) was taken for 24 weeks, in addition to the subject's current antiretroviral therapy (ART) drug regimen. At week 24, subjects discontinued MVC and were followed for an additional 24 weeks off MVC, but still on current ART drug regimen.

Participant Flow:   Overall Study
    Maraviroc  
STARTED     34  
Week 22/24     33  
COMPLETED     32  
NOT COMPLETED     2  
Withdrawal by Subject                 1  
Unable to attend clinic visits                 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 (MVC) was taken for 24 weeks, in addition to the subject's current antiretroviral therapy (ART) drug regimen. At week 24, subjects discontinued MVC and were followed for an additional 24 weeks off MVC, but still on current ART drug regimen.

Baseline Measures
    Maraviroc  
Number of Participants  
[units: participants]
  34  
Age  
[units: years]
Median ( Inter-Quartile Range )
  50  
  ( 47 to 55 )  
Gender  
[units: participants]
 
Female     2  
Male     32  
Race/Ethnicity, Customized  
[units: participants]
 
White Non-Hispanic     24  
Black Non-Hispanic     6  
Hispanic (Regardless of Race)     4  
Baseline CD4+ T-cell count [1]
[units: cells/mm^3]
Median ( Inter-Quartile Range )
  153  
  ( 119 to 203 )  
Baseline CD4 percentage [2]
[units: % of total lymphocytes]
Median ( Inter-Quartile Range )
  13  
  ( 10 to 17 )  
Baseline CD8+ T-cell count [3]
[units: cells/mm^3]
Median ( Inter-Quartile Range )
  559  
  ( 416 to 872 )  
Time with suppressed HIV-1 RNA prior to study entry [4]
[units: years]
Median ( Inter-Quartile Range )
  3.0  
  ( 1.8 to 4.5 )  
[1] Baseline CD4+ T-cell count is the average (mean) of the pre-entry and entry values
[2] Baseline CD4 percentage is the average (mean) of the pre-entry and entry values
[3] Baseline CD8+ T-cell count is the average (mean) of the pre-entry and entry values
[4] Four (4) participants had no documentation or recall of the date when they became suppressed (HIV-1 RNA <400 copies/ml)



  Outcome Measures
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1.  Primary:   Change in CD4+ T-cell Count   [ Time Frame: From baseline to week 24 ]

2.  Secondary:   Proportion of Participants Achieving a 50-cell Increase in CD4+ T-cell Count   [ Time Frame: From baseline to week 24 ]

3.  Secondary:   Within-subject CD4+ T-cell Count Slopes   [ Time Frame: From baseline through week 24 ]

4.  Secondary:   Change From Within-subject Pre-treatment CD4+ T-cell Count Slopes to Corresponding Within-subject CD4+ T-cell Count Slopes From Baseline Through Week 24   [ Time Frame: From pre-treatment through week 24 ]

5.  Secondary:   Change in CD4+ T-cell Count   [ Time Frame: From week 24 to week 36 ]

6.  Secondary:   Change in CD4+ T-cell Count   [ Time Frame: From week 24 to week 48 ]

7.  Secondary:   Change in CD4 Percentage   [ Time Frame: From baseline to week 24 ]

8.  Secondary:   Within-subject CD4 Percentage Slopes   [ Time Frame: From baseline through week 24 ]

9.  Secondary:   Change From Within-subject Pre-treatment CD4 Percentage Slopes to Corresponding Within-subject CD4 Percentage Slopes From Baseline Through Week 24   [ Time Frame: From pre-treatment through week 24 ]

10.  Secondary:   Change in CD4 Percentage   [ Time Frame: From week 24 to week 36 ]

11.  Secondary:   Change in CD4 Percentage   [ Time Frame: From week 24 to week 48 ]

12.  Secondary:   Number of Subjects Who Experience a Grade 2, 3 or 4 Signs and Symptoms, Grade 3 or 4 Laboratory Abnormalities, or Death.   [ Time Frame: From baseline through week 24 ]

13.  Secondary:   Change in Percentage of CD4+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+   [ Time Frame: From baseline to week 24 ]

14.  Secondary:   Change in Percentage of CD8+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+   [ Time Frame: From baseline to week 24 ]

15.  Secondary:   Change in Percentage of CD4+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+   [ Time Frame: From week 24 to week 36 ]

16.  Secondary:   Change in Percentage of CD8+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+   [ Time Frame: From week 24 to week 36 ]

17.  Secondary:   Change in Percentage of CD4+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+   [ Time Frame: From week 24 to week 48 ]

18.  Secondary:   Change in Percentage of CD8+ T-cells That Are: naïve (%CD45RA+CCR7+), Central Memory (%CD45RA-CCR7+), Effector Memory (%CD45RA-CCR7-), Effector (%CD45RA+CCR7-), %HLA-DR+CD38+, %CD38+, %Ki67+, %caspase3+, %Bcl-2-, and %CD57+   [ Time Frame: From week 24 to week 48 ]

19.  Secondary:   Change in Soluble CD14   [ Time Frame: From baseline to week 24 ]

20.  Secondary:   Change in Soluble CD14   [ Time Frame: From week 24 to week 36 ]

21.  Secondary:   Change in Soluble CD14   [ Time Frame: From week 24 to week 48 ]

22.  Secondary:   Change in High Sensitivity C-reactive Protein (Hs-CRP)   [ Time Frame: From baseline to week 24 ]

23.  Secondary:   Change in Interleukin (IL)-6, Monocyte Chemoattractant Protein (MCP)-1, MCP-2, and Plasma CD40 Ligand (CD40L)   [ Time Frame: From baseline to week 24 ]

24.  Secondary:   Change in Intercellular Cell Adhesion Molecule (ICAM)-1, Plasma P-selectin, Soluble TNFRII (sTNFRII), and Matrix Metalloproteinase (MMP)-9   [ Time Frame: From baseline to week 24 ]

25.  Secondary:   Change in D-dimer   [ Time Frame: From baseline to week 24 ]

26.  Secondary:   Change in Hs-CRP   [ Time Frame: From week 24 to week 36 ]

27.  Secondary:   Change in IL-6, MCP-1, MCP-2, and Plasma CD40L   [ Time Frame: From week 24 to week 36 ]

28.  Secondary:   Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9   [ Time Frame: From week 24 to week 36 ]

29.  Secondary:   Change in D-dimer   [ Time Frame: From week 24 to week 36 ]

30.  Secondary:   Change in Hs-CRP   [ Time Frame: From week 24 to week 48 ]

31.  Secondary:   Change in IL-6, MCP-1, MCP-2, and Plasma CD40L   [ Time Frame: From week 24 to week 48 ]

32.  Secondary:   Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9   [ Time Frame: From week 24 to week 48 ]

33.  Secondary:   Change in D-dimer   [ Time Frame: From week 24 to week 48 ]

34.  Secondary:   Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA)   [ Time Frame: At weeks -1 (pre-entry), 0 (entry), 12, 22, 24, and 36 ]

35.  Secondary:   Drug Adherence Assessed as Number of Missed Doses Over a 4-day Recall   [ Time Frame: At weeks 4, 12, and 24 ]


  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
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinicaltrials.gov Coordinator
Organization: Center for Biostatistics in AIDS Research, Harvard School of Public Health
phone: (617) 432-2829
e-mail: CBAR.ClinicalTrials.Gov@sdac.harvard.edu


Publications of Results:
Wilkin T, Lalama C, Tenorio A, Landay A, Ribaudo H, McKinnon J, Gandhi R, Mellors J, Currier J, and Gulick R. Maraviroc Intensification for Suboptimal CD4+ Cell Response Despite Sustained Virologic Suppression: ACTG 5256. 17th Conference on Retroviruses and Opportunistic Infections, San Francisco, CA, February 16-19, 2010.
Wilkin T, Lalama C, Tenorio A, Landay A, Fox L, McKinnon J, Gandhi R, Mellors J, Currier J, Gulick R. ACTG 5256: Effect of adding and removing maraviroc (MVC) on immune activation in participants on suppressive antiretroviral therapy (ART). 18th Conference on Retroviruses and Opportunistic Infections, Boston, MA, February 27-March 02, 2011.

Other Publications:
Publications automatically indexed to this study:

Responsible Party: AIDS Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00709111     History of Changes
Other Study ID Numbers: ACTG A5256, 1U01AI068636
Study First Received: July 1, 2008
Results First Received: July 26, 2011
Last Updated: January 23, 2012
Health Authority: United States: Federal Government