search
Back to results

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

Primary Purpose

HIV Infections

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Maraviroc
Sponsored by
AIDS Clinical Trials Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring CCR5 antagonist, CD4 T-cell count, immune activation, treatment experienced

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • HIV-1 infection
  • On ART for at least 48 weeks prior to study entry with a regimen that includes three or more antiretroviral medications
  • No change in ART regimen for at least 24 weeks prior to study entry
  • Screening CD4+ T-cell count less than 250 obtained within 60 days prior to study entry
  • Stable CD4+ T-cell count for at least 48 weeks prior to study entry (as assessed by an estimated CD4+ T-cell count slope between -20 and +20 cells/year)
  • Screening HIV-1 RNA below the limit of detection using an FDA-approved assay obtained within 60 days prior to study entry
  • All other plasma HIV-1 RNA measurements in the 48 weeks prior to study entry must be below the limit of detection

  • Laboratory values obtained within 60 days prior to study entry:

    • Absolute neutrophil count (ANC) >=750/µL
    • Hemoglobin >=9.0 g/dL for female subjects and >=10.0 g/dL for male subjects
    • Platelet count >=50,000/ µL
    • Calculated creatinine clearance (CrCl) >=30 mL/min
    • Aspartate aminotransferase (serum glutamic oxaloacetic transaminase), alanine aminotransferase (serum glutamic pyruvic transaminase), and alkaline phosphatase <=5 X Upper Limit of Normal (ULN)
    • Direct bilirubin <=2.5 X ULN
  • Females of reproductive potential will need a negative serum or urine pregnancy test within 48 hours prior to study entry
  • Agree not to participate in the conception process, and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least two reliable forms of contraceptives while receiving study treatment and for 6 weeks after stopping study treatment.

Exclusion Criteria:

  • Unstable clinical condition
  • Currently breast-feeding or pregnant
  • Use of immunomodulators or cancer chemotherapy or radiation treatment within 12 months prior to study entry
  • An acute AIDS-defining illness within 60 days prior to study entry
  • Known allergy/sensitivity or hypersensitivity to components of MVC, including allergy or hypersensitivity to soya lecithin, soya or peanuts
  • Active drug or alcohol abuse that, in the opinion of the investigator, would interfere with adherence to study regimens
  • Serious illness requiring systemic treatment and/or hospitalization within 60 days prior to study entry
  • Receipt of a vaccine within 30 days prior to study entry
  • Current or previous use of a CCR5 inhibitor
  • Plan to change background ART regimen within 24 weeks after study entry
  • Receipt of experimental or non-experimental medications for the purpose of raising CD4+ T-cell counts within 6 months prior to study entry

Sites / Locations

  • Alabama Therapeutics CRS (5801)
  • UCLA CARE Center CRS (601)
  • Stanford CRS (501)
  • Ucsd, Avrc Crs (701)
  • Ucsf Aids Crs (801)
  • Georgetown University CRS (GU CRS) (1008)
  • Univ. of Miami AIDS CRS (901)
  • The Ponce de Leon Ctr. CRS (5802)
  • Northwestern University CRS (2701)
  • IHV Baltimore Treatment CRS (4651)
  • Johns Hopkins Adult AIDS CRS (201)
  • Massachusetts General Hospital ACTG CRS (101)
  • Brigham and Women's Hosp. ACTG CRS (107)
  • Boston Medical Center ACTG CRS (104)
  • Washington University CRS (2101)
  • Cornell CRS (7804)
  • NY Univ. HIV/AIDS CRS (401)
  • AIDS Care CRS (1108)
  • Univ. of Rochester ACTG CRS (1101)
  • Unc Aids Crs (3201)
  • Duke Univ. Med. Ctr. Adult CRS (1601)
  • Univ. of Cincinnati CRS (2401)
  • MetroHealth CRS (2503)
  • The Ohio State Univ. AIDS CRS (2301)
  • Hosp. of the Univ. of Pennsylvania CRS (6201)
  • Pittsburgh CRS (1001)
  • Vanderbilt Therapeutics CRS (3652)
  • Peabody Health Ctr. CRS (31443)
  • Houston AIDS Research Team CRS (31473)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Maraviroc

Arm Description

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.

Outcomes

Primary Outcome Measures

Change in CD4+ T-cell Count
Change was calculated as the week 24 CD4+ T-cell count (average of the week 22 and week 24 values) minus the baseline CD4+ T-cell count (average of pre-entry and entry values).

Secondary Outcome Measures

Proportion of Participants Achieving a 50-cell Increase in CD4+ T-cell Count
Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Within-subject CD4+ T-cell Count Slopes
The estimated mean slope was summarized across the population by using generalized estimating equations. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
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
The estimated mean change in slopes was summarized across the population by using generalized estimating equations. Pre-treatment CD4+ T-cell counts (from at least 48 weeks prior to study entry) were recorded at screening from patient source documentation. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Change in CD4+ T-cell Count
Change was calculated as week 36 CD4+ T-cell count minus the week 24 CD4+ T-cell count (average of the week 22 and week 24 values).
Change in CD4+ T-cell Count
Change was calculated as week 48 CD4+ T-cell count (average of week 46 and week 48) minus the week 24 CD4+ T-cell count (average of the week 22 and week 24 values).
Change in CD4 Percentage
Change was calculated as the week 24 CD4 percentage (average of the week 22 and week 24 values) minus the baseline CD4 percentage (average of pre-entry and entry values).
Within-subject CD4 Percentage Slopes
The estimated mean slope was summarized across the population by using generalized estimating equations. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Change From Within-subject Pre-treatment CD4 Percentage Slopes to Corresponding Within-subject CD4 Percentage Slopes From Baseline Through Week 24
The estimated mean change in slopes was summarized across the population by using generalized estimating equations. Pre-treatment CD4 percentage (from at least 48 weeks prior to study entry) were recorded at screening from patient source documentation. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Change in CD4 Percentage
Change was calculated as week 36 CD4 percentage minus the week 24 CD4 percentage (average of the week 22 and week 24 values).
Change in CD4 Percentage
Change was calculated as week 48 CD4 percentage (average of week 46 and week 48) minus the week 24 CD4 percentage (average of the week 22 and week 24 values).
Number of Subjects Who Experience a Grade 2, 3 or 4 Signs and Symptoms, Grade 3 or 4 Laboratory Abnormalities, or Death.
Events with date of onset or specimen date prior to first dose of MVC or after the last dose of MVC were excluded. Signs and symptoms with a date of onset the same as the first dose of MVC were excluded if confirmed by the site to be before the first dose. Lab abnormalities with the date of specimen the same as the date of the first dose of MVC were excluded on the assumption that the specimen was drawn before the first dose. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life-threatening.
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+
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
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+
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
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+
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
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+
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
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+
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
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+
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Change in Soluble CD14
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values). Soluble CD14 is a marker of gut microbial translocation.
Change in Soluble CD14
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values). Soluble CD14 is a marker of gut microbial translocation.
Change in Soluble CD14
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values). Soluble CD14 is a marker of gut microbial translocation.
Change in High Sensitivity C-reactive Protein (Hs-CRP)
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Change in Interleukin (IL)-6, Monocyte Chemoattractant Protein (MCP)-1, MCP-2, and Plasma CD40 Ligand (CD40L)
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Change in Intercellular Cell Adhesion Molecule (ICAM)-1, Plasma P-selectin, Soluble TNFRII (sTNFRII), and Matrix Metalloproteinase (MMP)-9
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Change in D-dimer
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Change in Hs-CRP
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Change in IL-6, MCP-1, MCP-2, and Plasma CD40L
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Change in D-dimer
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Change in Hs-CRP
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Change in IL-6, MCP-1, MCP-2, and Plasma CD40L
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Change in D-dimer
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA)
A subject was considered detectable at a specific week if HIV-1 RNA by SCA >=1 copy/ml.
Drug Adherence Assessed as Number of Missed Doses Over a 4-day Recall
Self-reported MVC adherence data were based on a four-day (8 expected doses) recall. Based on the wording of the Self Report case report form (CRF), participants reporting that they were currently taking MVC that then failed to complete the record of the number of missed doses were assumed to have no missed doses to report. Missing adherence assessments at a time point of interest were ignored and only those participants completing an adherence assessment at least one time point of interest were included.

Full Information

First Posted
July 1, 2008
Last Updated
September 11, 2018
Sponsor
AIDS Clinical Trials Group
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
search

1. Study Identification

Unique Protocol Identification Number
NCT00709111
Brief Title
Adding Maraviroc to Antiretroviral Therapy for Suboptimal CD4 T-Cell Recovery Despite Sustained Virologic Suppression
Official Title
A Pilot Trial of Maraviroc for Treatment of Subjects on Antiretroviral Therapy With Suboptimal CD4 T-cell Count Recovery Despite Sustained Virologic Suppression
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
January 2009 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
April 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AIDS Clinical Trials Group
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Despite viral suppression, antiretroviral therapy (ART) does not restore CD4+ T-cell counts in some subjects. The purpose of this study is to assess whether adding maraviroc (MVC) to a suppressive ART will result in a significant CD4+ T-cell count increase over 24 weeks in subjects with suboptimal CD4+ T-cell recovery despite sustained virologic suppression.
Detailed Description
The majority of HIV-infected subjects with virologic suppression on antiretroviral therapy (ART) have a marked increase in CD4+ T-cell counts over the first year on treatment. However, a portion of these individuals show a suboptimal immune response and remain at an elevated risk for disease progression. The use of the CCR5 inhibitor maraviroc (MVC) is associated with enhanced CD4+ T-cell recovery in subjects who initiate ART. AIDS Clinical Trials Group (ACTG) A5256 studied the effect of ART intensification with MVC on CD4+ T-cell counts in subjects with suboptimal CD4 recovery despite sustained virologic suppression. Eligible subjects added MVC to their ART regimen, and continued MVC for 24 weeks. At week 24, subjects discontinued MVC and were followed for an additional 24 weeks off MVC. Subjects were seen through week 48 for clinical and laboratory evaluations, including plasma HIV-1 RNA, CD4+ T-cell count, and safety laboratories. Subjects had 2 baseline visits prior to starting MVC. Study visits were scheduled at weeks 4, 8, 12, 16, 22, 24, 36, 46, and 48. CD4+ T-cell counts were measured at every study visit and HIV-1 RNA at weeks 12, 24, 36, and 48, regardless of treatment status. Measures of activation, T-cell maturation, and apoptosis were performed at all weeks except 4, 8, and 16. At the end of the study, the pre-entry, entry, week 12, 22, 24, and 36 samples for the HIV-1 RNA by single-copy assay (SCA) were run. The week 46 and 48 samples were not run.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
CCR5 antagonist, CD4 T-cell count, immune activation, treatment experienced

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
34 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Maraviroc
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Maraviroc
Other Intervention Name(s)
MVC, Selzentry
Intervention Description
The maraviroc doses were 150 mg orally twice daily, 300 mg orally twice daily, or 600 mg orally twice daily, depending on the pharmacokinetic interaction with a subject's pre-study ART and non-ART drug regimen according to the package insert.
Primary Outcome Measure Information:
Title
Change in CD4+ T-cell Count
Description
Change was calculated as the week 24 CD4+ T-cell count (average of the week 22 and week 24 values) minus the baseline CD4+ T-cell count (average of pre-entry and entry values).
Time Frame
From baseline to week 24
Secondary Outcome Measure Information:
Title
Proportion of Participants Achieving a 50-cell Increase in CD4+ T-cell Count
Description
Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Time Frame
From baseline to week 24
Title
Within-subject CD4+ T-cell Count Slopes
Description
The estimated mean slope was summarized across the population by using generalized estimating equations. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Time Frame
From baseline through week 24
Title
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
Description
The estimated mean change in slopes was summarized across the population by using generalized estimating equations. Pre-treatment CD4+ T-cell counts (from at least 48 weeks prior to study entry) were recorded at screening from patient source documentation. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Time Frame
From pre-treatment through week 24
Title
Change in CD4+ T-cell Count
Description
Change was calculated as week 36 CD4+ T-cell count minus the week 24 CD4+ T-cell count (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 36
Title
Change in CD4+ T-cell Count
Description
Change was calculated as week 48 CD4+ T-cell count (average of week 46 and week 48) minus the week 24 CD4+ T-cell count (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 48
Title
Change in CD4 Percentage
Description
Change was calculated as the week 24 CD4 percentage (average of the week 22 and week 24 values) minus the baseline CD4 percentage (average of pre-entry and entry values).
Time Frame
From baseline to week 24
Title
Within-subject CD4 Percentage Slopes
Description
The estimated mean slope was summarized across the population by using generalized estimating equations. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Time Frame
From baseline through week 24
Title
Change From Within-subject Pre-treatment CD4 Percentage Slopes to Corresponding Within-subject CD4 Percentage Slopes From Baseline Through Week 24
Description
The estimated mean change in slopes was summarized across the population by using generalized estimating equations. Pre-treatment CD4 percentage (from at least 48 weeks prior to study entry) were recorded at screening from patient source documentation. Baseline was defined as the average of pre-entry and entry values. Week 24 was defined as the average of the week 22 and week 24 values.
Time Frame
From pre-treatment through week 24
Title
Change in CD4 Percentage
Description
Change was calculated as week 36 CD4 percentage minus the week 24 CD4 percentage (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 36
Title
Change in CD4 Percentage
Description
Change was calculated as week 48 CD4 percentage (average of week 46 and week 48) minus the week 24 CD4 percentage (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 48
Title
Number of Subjects Who Experience a Grade 2, 3 or 4 Signs and Symptoms, Grade 3 or 4 Laboratory Abnormalities, or Death.
Description
Events with date of onset or specimen date prior to first dose of MVC or after the last dose of MVC were excluded. Signs and symptoms with a date of onset the same as the first dose of MVC were excluded if confirmed by the site to be before the first dose. Lab abnormalities with the date of specimen the same as the date of the first dose of MVC were excluded on the assumption that the specimen was drawn before the first dose. Grading used the Division of AIDS (DAIDS) 2004 Severity of Adverse Events Tables, where Grade 1=Mild, 2=Moderate, 3=Severe, 4=Potentially life-threatening.
Time Frame
From baseline through week 24
Title
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+
Description
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Time Frame
From baseline to week 24
Title
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+
Description
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Time Frame
From baseline to week 24
Title
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+
Description
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 36
Title
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+
Description
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 36
Title
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+
Description
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 48
Title
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+
Description
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 48
Title
Change in Soluble CD14
Description
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values). Soluble CD14 is a marker of gut microbial translocation.
Time Frame
From baseline to week 24
Title
Change in Soluble CD14
Description
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values). Soluble CD14 is a marker of gut microbial translocation.
Time Frame
From week 24 to week 36
Title
Change in Soluble CD14
Description
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values). Soluble CD14 is a marker of gut microbial translocation.
Time Frame
From week 24 to week 48
Title
Change in High Sensitivity C-reactive Protein (Hs-CRP)
Description
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Time Frame
From baseline to week 24
Title
Change in Interleukin (IL)-6, Monocyte Chemoattractant Protein (MCP)-1, MCP-2, and Plasma CD40 Ligand (CD40L)
Description
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Time Frame
From baseline to week 24
Title
Change in Intercellular Cell Adhesion Molecule (ICAM)-1, Plasma P-selectin, Soluble TNFRII (sTNFRII), and Matrix Metalloproteinase (MMP)-9
Description
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Time Frame
From baseline to week 24
Title
Change in D-dimer
Description
Change was calculated as the week 24 result (average of the week 22 and week 24 values) minus the baseline result (average of pre-entry and entry values).
Time Frame
From baseline to week 24
Title
Change in Hs-CRP
Description
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 36
Title
Change in IL-6, MCP-1, MCP-2, and Plasma CD40L
Description
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 36
Title
Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9
Description
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 36
Title
Change in D-dimer
Description
Change was calculated as week 36 result minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 36
Title
Change in Hs-CRP
Description
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 48
Title
Change in IL-6, MCP-1, MCP-2, and Plasma CD40L
Description
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 48
Title
Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9
Description
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 48
Title
Change in D-dimer
Description
Change was calculated as week 48 result (average of week 46 and week 48) minus the week 24 result (average of the week 22 and week 24 values).
Time Frame
From week 24 to week 48
Title
Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA)
Description
A subject was considered detectable at a specific week if HIV-1 RNA by SCA >=1 copy/ml.
Time Frame
At weeks -1 (pre-entry), 0 (entry), 12, 22, 24, and 36
Title
Drug Adherence Assessed as Number of Missed Doses Over a 4-day Recall
Description
Self-reported MVC adherence data were based on a four-day (8 expected doses) recall. Based on the wording of the Self Report case report form (CRF), participants reporting that they were currently taking MVC that then failed to complete the record of the number of missed doses were assumed to have no missed doses to report. Missing adherence assessments at a time point of interest were ignored and only those participants completing an adherence assessment at least one time point of interest were included.
Time Frame
At weeks 4, 12, and 24

10. Eligibility

Sex
All
Minimum Age & Unit of Time
16 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: HIV-1 infection On ART for at least 48 weeks prior to study entry with a regimen that includes three or more antiretroviral medications No change in ART regimen for at least 24 weeks prior to study entry Screening CD4+ T-cell count less than 250 obtained within 60 days prior to study entry Stable CD4+ T-cell count for at least 48 weeks prior to study entry (as assessed by an estimated CD4+ T-cell count slope between -20 and +20 cells/year) Screening HIV-1 RNA below the limit of detection using an FDA-approved assay obtained within 60 days prior to study entry All other plasma HIV-1 RNA measurements in the 48 weeks prior to study entry must be below the limit of detection Laboratory values obtained within 60 days prior to study entry: Absolute neutrophil count (ANC) >=750/µL Hemoglobin >=9.0 g/dL for female subjects and >=10.0 g/dL for male subjects Platelet count >=50,000/ µL Calculated creatinine clearance (CrCl) >=30 mL/min Aspartate aminotransferase (serum glutamic oxaloacetic transaminase), alanine aminotransferase (serum glutamic pyruvic transaminase), and alkaline phosphatase <=5 X Upper Limit of Normal (ULN) Direct bilirubin <=2.5 X ULN Females of reproductive potential will need a negative serum or urine pregnancy test within 48 hours prior to study entry Agree not to participate in the conception process, and if participating in sexual activity that could lead to pregnancy, the subject/partner must use at least two reliable forms of contraceptives while receiving study treatment and for 6 weeks after stopping study treatment. Exclusion Criteria: Unstable clinical condition Currently breast-feeding or pregnant Use of immunomodulators or cancer chemotherapy or radiation treatment within 12 months prior to study entry An acute AIDS-defining illness within 60 days prior to study entry Known allergy/sensitivity or hypersensitivity to components of MVC, including allergy or hypersensitivity to soya lecithin, soya or peanuts Active drug or alcohol abuse that, in the opinion of the investigator, would interfere with adherence to study regimens Serious illness requiring systemic treatment and/or hospitalization within 60 days prior to study entry Receipt of a vaccine within 30 days prior to study entry Current or previous use of a CCR5 inhibitor Plan to change background ART regimen within 24 weeks after study entry Receipt of experimental or non-experimental medications for the purpose of raising CD4+ T-cell counts within 6 months prior to study entry
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Timothy J. Wilkin, MD, MPH
Organizational Affiliation
Cornell Clinical Research Site
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Roy Gulick, MD, MPH
Organizational Affiliation
Cornell HIV Clinical Trials Unit
Official's Role
Study Chair
Facility Information:
Facility Name
Alabama Therapeutics CRS (5801)
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
UCLA CARE Center CRS (601)
City
Los Angeles
State/Province
California
ZIP/Postal Code
90035
Country
United States
Facility Name
Stanford CRS (501)
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Ucsd, Avrc Crs (701)
City
San Diego
State/Province
California
ZIP/Postal Code
92103
Country
United States
Facility Name
Ucsf Aids Crs (801)
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
Georgetown University CRS (GU CRS) (1008)
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Univ. of Miami AIDS CRS (901)
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
The Ponce de Leon Ctr. CRS (5802)
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
Northwestern University CRS (2701)
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
IHV Baltimore Treatment CRS (4651)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Johns Hopkins Adult AIDS CRS (201)
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21205
Country
United States
Facility Name
Massachusetts General Hospital ACTG CRS (101)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Facility Name
Brigham and Women's Hosp. ACTG CRS (107)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Boston Medical Center ACTG CRS (104)
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Washington University CRS (2101)
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Cornell CRS (7804)
City
New York
State/Province
New York
ZIP/Postal Code
10011
Country
United States
Facility Name
NY Univ. HIV/AIDS CRS (401)
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
AIDS Care CRS (1108)
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Univ. of Rochester ACTG CRS (1101)
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Unc Aids Crs (3201)
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27516
Country
United States
Facility Name
Duke Univ. Med. Ctr. Adult CRS (1601)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Univ. of Cincinnati CRS (2401)
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
MetroHealth CRS (2503)
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44109
Country
United States
Facility Name
The Ohio State Univ. AIDS CRS (2301)
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Hosp. of the Univ. of Pennsylvania CRS (6201)
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Pittsburgh CRS (1001)
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Vanderbilt Therapeutics CRS (3652)
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37204
Country
United States
Facility Name
Peabody Health Ctr. CRS (31443)
City
Dallas
State/Province
Texas
ZIP/Postal Code
75215
Country
United States
Facility Name
Houston AIDS Research Team CRS (31473)
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
18174962
Citation
Fadel H, Temesgen Z. Maraviroc. Drugs Today (Barc). 2007 Nov;43(11):749-58. doi: 10.1358/dot.2007.43.11.1131763.
Results Reference
background
PubMed Identifier
18532888
Citation
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. doi: 10.1086/589289.
Results Reference
background
Citation
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.
Results Reference
result
Citation
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.
Results Reference
result
Citation
Hilldorfer B, Lalama C, McKinnon J, Coombs B, Tenorio A, Fox L, Gandhi R, Ribaudo H, Currier J, Gulick R, Wilkin TJ, Mellors J. Effects of Maraviroc (MVC) on Residual Low-Level Viremia in Patients on Suppressive Antiretroviral Therapy (ART): Results from ACTG 5256. 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy, July 17-20, 2011.
Results Reference
result
PubMed Identifier
22740718
Citation
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. doi: 10.1093/infdis/jis376. Epub 2012 Jun 27.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs