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

This study has been completed.

Sponsor:

Collaborator:

National Institute of Allergy and Infectious Diseases (NIAID)

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

History of Changes

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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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 ]

Show Outcome Measure 1

2. Secondary:

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

Show Outcome Measure 2

3. Secondary:

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

Show Outcome Measure 3

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 ]

Show Outcome Measure 4

5. Secondary:

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

Show Outcome Measure 5

6. Secondary:

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

Show Outcome Measure 6

7. Secondary:

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

Show Outcome Measure 7

8. Secondary:

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

Show Outcome Measure 8

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 ]

Show Outcome Measure 9

10. Secondary:

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

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11. Secondary:

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

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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 ]

Show Outcome Measure 12

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 ]

Show Outcome Measure 13

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 ]

Show Outcome Measure 14

15. Secondary:

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16. Secondary:

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17. Secondary:

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18. Secondary:

Show Outcome Measure 18

19. Secondary:

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

Show Outcome Measure 19

20. Secondary:

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

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21. Secondary:

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

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22. Secondary:

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

Show Outcome Measure 22

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 ]

Show Outcome Measure 23

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 ]

Show Outcome Measure 24

25. Secondary:

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

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26. Secondary:

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

Show Outcome Measure 26

27. Secondary:

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

Show Outcome Measure 27

28. Secondary:

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

Show Outcome Measure 28

29. Secondary:

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

Show Outcome Measure 29

30. Secondary:

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

Show Outcome Measure 30

31. Secondary:

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

Show Outcome Measure 31

32. Secondary:

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

Show Outcome Measure 32

33. Secondary:

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

Show Outcome Measure 33

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 ]

Show Outcome Measure 34

35. Secondary:

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

Show Outcome Measure 35

Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: In accordance with the Clinical Trial Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights

Limitations and Caveats

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.

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:

Fadel H, Temesgen Z. Maraviroc. Drugs Today (Barc). 2007 Nov;43(11):749-58. Review.

MacArthur RD, Novak RM. Reviews of anti-infective agents: maraviroc: the first of a new class of antiretroviral agents. Clin Infect Dis. 2008 Jul 15;47(2):236-41.

Publications automatically indexed to this study:

Wilkin TJ, Lalama CM, McKinnon J, Gandhi RT, Lin N, Landay A, Ribaudo H, Fox L, Currier JS, Mellors JW, Gulick R, Tenorio AR. A pilot trial of adding maraviroc to suppressive antiretroviral therapy for suboptimal CD4⁺ T-cell recovery despite sustained virologic suppression: ACTG A5256. J Infect Dis. 2012 Aug 15;206(4):534-42. Epub 2012 Jun 27.

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

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