HIV Infections
Conditions
Keywords
CCR5 antagonist, CD4 T-cell count, immune activation, treatment experienced
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.
Interventions
DRUGMaraviroc
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.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CD4+ T-cell Count | From baseline to week 24 | 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
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Achieving a 50-cell Increase in CD4+ T-cell Count | From baseline to week 24 | 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 | From pre-treatment 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 | From week 24 to week 36 | 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 Percentage | From baseline to week 24 | 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 | From baseline through week 24 | 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 | From pre-treatment 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. |
| Number of Subjects Who Experience a Grade 2, 3 or 4 Signs and Symptoms, Grade 3 or 4 Laboratory Abnormalities, or Death. | From baseline through week 24 | 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+ | From baseline to week 24 | 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+ | From baseline to week 24 | 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). |
| Within-subject CD4+ T-cell Count Slopes | From baseline through week 24 | 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 in High Sensitivity C-reactive Protein (Hs-CRP) | From baseline to week 24 | 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) | From baseline to week 24 | 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 | From baseline to week 24 | 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 | From baseline to week 24 | 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 | From week 24 to week 36 | 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 | From week 24 to week 36 | 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 | From week 24 to week 36 | Change was calculated as week 36 result 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) | At weeks -1 (pre-entry), 0 (entry), 12, 22, 24, and 36 | 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 | At weeks 4, 12, and 24 | 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. |
| Change in Soluble CD14 | From baseline to week 24 | 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. |
Countries
United States
Participant flow
Recruitment details
Recruited at 29 AIDS Clinical Trials Units in the United States between January 14, 2009 and May 4, 2009
Pre-assignment details
34 enrolled
Participants by arm
| Arm | Count |
|---|---|
| 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. | 34 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Unable to attend clinic visits | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Maraviroc |
|---|---|
| Age, Continuous | 50 years |
| Baseline CD4 percentage | 13 % of total lymphocytes |
| Baseline CD4+ T-cell count | 153 cells/mm^3 |
| Baseline CD8+ T-cell count | 559 cells/mm^3 |
| Race/Ethnicity, Customized Black Non-Hispanic | 6 participants |
| Race/Ethnicity, Customized Hispanic (Regardless of Race) | 4 participants |
| Race/Ethnicity, Customized White Non-Hispanic | 24 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 32 Participants |
| Time with suppressed HIV-1 RNA prior to study entry | 3.0 years |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 34 |
| serious Total, serious adverse events | 4 / 34 |
Outcome results
Primary
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).
Time frame: From baseline to week 24
Population: As-treated: Only participants with either a week 22 CD4+ T-cell count or a week 24 CD4+ T-cell count obtained while receiving MVC without change in background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in CD4+ T-cell Count | 12 cells/mm^3 |
Comparison: The change in CD4+ T-cell count from baseline to week 24 was compared against the null hypothesis of change \<20 cells/mm\^3. The study was powered to yield 80% power to show that there was \>=20 cells/mm\^3 increase in CD4+ T-cell count assuming an underlying change in CD4+ T-cell counts induced by MVC of 50 cells/mm\^3, a standard deviation of 60 cells/mm\^3 around the mean CD4+ T-cell count change, 10% lost-to-follow-up or premature MVC discontinuation rate, and one-sided type 1 error of 0.05.p-value: 0.97Wilcoxon signed-rank, 1-sided
Secondary
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.
Time frame: From pre-treatment through week 24
Population: As-treated: Participants with CD4 percentage available at least through visit week 22 while receiving MVC without change in background regimen were included. Four of these subjects did not have pre-treatment (from at least 48 weeks prior to study entry) CD4 percentage results available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Maraviroc | Change From Within-subject Pre-treatment CD4 Percentage Slopes to Corresponding Within-subject CD4 Percentage Slopes From Baseline Through Week 24 | -1.0 % of total lymphocytes/year |
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
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
Population: As-treated: Participants with CD4+ T-cell counts available at least through visit week 22 while receiving MVC without change in background regimen were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Maraviroc | 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 | 25.2 cells/mm^3/year |
Secondary
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).
Time frame: From week 24 to week 48
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with either a week 46 CD4 percentage or a week 48 CD4 percentage obtained while receiving background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in CD4 Percentage | 0.5 % of total lymphocytes |
Secondary
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).
Time frame: From baseline to week 24
Population: As-treated: Only participants with either a week 22 CD4 percentage or a week 24 CD4 percentage obtained while receiving MVC without change in background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in CD4 Percentage | 0.5 % of total lymphocytes |
Secondary
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).
Time frame: From week 24 to week 36
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with a week 36 CD4 percentage obtained while receiving background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in CD4 Percentage | 0.2 % of total lymphocytes |
Secondary
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).
Time frame: From week 24 to week 48
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with either a week 46 CD4+ T-cell count or a week 48 CD4+ T-cell count obtained while receiving background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in CD4+ T-cell Count | 7 cells/mm^3 |
Secondary
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).
Time frame: From week 24 to week 36
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with a week 36 CD4+ T-cell count obtained while receiving background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in CD4+ T-cell Count | -3 cells/mm^3 |
Secondary
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).
Time frame: From baseline to week 24
Population: As-treated: Only participants with either a week 22 result or a week 24 result obtained while receiving MVC without change in background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in D-dimer | 0.09 mcg/ml |
Secondary
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).
Time frame: From week 24 to week 36
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with a week 36 result obtained while receiving background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in D-dimer | 0.01 mcg/ml |
Secondary
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).
Time frame: From week 24 to week 48
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with either a week 46 result or a week 48 result obtained while receiving background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in D-dimer | -0.02 mcg/ml |
Secondary
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).
Time frame: From baseline to week 24
Population: As-treated: Only participants with either a week 22 result or a week 24 result obtained while receiving MVC without change in background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in High Sensitivity C-reactive Protein (Hs-CRP) | 0.01 mg/dl |
Secondary
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).
Time frame: From week 24 to week 36
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with a week 36 result obtained while receiving background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in Hs-CRP | -0.01 mg/dl |
Secondary
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).
Time frame: From week 24 to week 48
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with either a week 46 result or a week 48 result obtained while receiving background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in Hs-CRP | 0.01 mg/dl |
Secondary
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).
Time frame: From week 24 to week 48
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with either a week 46 result or a week 48 result obtained while receiving background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9 | ICAM-1 | -32.4 ng/ml |
| Maraviroc | Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9 | P-selectin | -17.3 ng/ml |
| Maraviroc | Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9 | sTNFRII | 0.03 ng/ml |
| Maraviroc | Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9 | MMP-9 | 12.8 ng/ml |
Secondary
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).
Time frame: From week 24 to week 36
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with a week 36 result obtained while receiving background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9 | ICAM-1 | -20.9 ng/ml |
| Maraviroc | Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9 | P-selectin | -13.7 ng/ml |
| Maraviroc | Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9 | sTNFRII | -0.05 ng/ml |
| Maraviroc | Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9 | MMP-9 | 11.3 ng/ml |
Secondary
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).
Time frame: From week 24 to week 36
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with a week 36 result obtained while receiving background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | Change in IL-6, MCP-1, MCP-2, and Plasma CD40L | IL-6 | -0.9 pg/ml |
| Maraviroc | Change in IL-6, MCP-1, MCP-2, and Plasma CD40L | MCP-1 | -6.9 pg/ml |
| Maraviroc | Change in IL-6, MCP-1, MCP-2, and Plasma CD40L | MCP-2 | 0.1 pg/ml |
| Maraviroc | Change in IL-6, MCP-1, MCP-2, and Plasma CD40L | CD40L | 0 pg/ml |
Secondary
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).
Time frame: From week 24 to week 48
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with either a week 46 result or a week 48 result obtained while receiving background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | Change in IL-6, MCP-1, MCP-2, and Plasma CD40L | IL-6 | -0.5 pg/ml |
| Maraviroc | Change in IL-6, MCP-1, MCP-2, and Plasma CD40L | MCP-1 | 7.7 pg/ml |
| Maraviroc | Change in IL-6, MCP-1, MCP-2, and Plasma CD40L | MCP-2 | 0.2 pg/ml |
| Maraviroc | Change in IL-6, MCP-1, MCP-2, and Plasma CD40L | CD40L | 32.3 pg/ml |
Secondary
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).
Time frame: From baseline to week 24
Population: As-treated: Only participants with either a week 22 result or a week 24 result obtained while receiving MVC without change in background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | Change in Intercellular Cell Adhesion Molecule (ICAM)-1, Plasma P-selectin, Soluble TNFRII (sTNFRII), and Matrix Metalloproteinase (MMP)-9 | ICAM-1 | -25.7 ng/ml |
| Maraviroc | Change in Intercellular Cell Adhesion Molecule (ICAM)-1, Plasma P-selectin, Soluble TNFRII (sTNFRII), and Matrix Metalloproteinase (MMP)-9 | P-selectin | -11.7 ng/ml |
| Maraviroc | Change in Intercellular Cell Adhesion Molecule (ICAM)-1, Plasma P-selectin, Soluble TNFRII (sTNFRII), and Matrix Metalloproteinase (MMP)-9 | sTNFRII | 0.18 ng/ml |
| Maraviroc | Change in Intercellular Cell Adhesion Molecule (ICAM)-1, Plasma P-selectin, Soluble TNFRII (sTNFRII), and Matrix Metalloproteinase (MMP)-9 | MMP-9 | -12.5 ng/ml |
Secondary
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).
Time frame: From baseline to week 24
Population: As-treated: Only participants with either a week 22 result or a week 24 result obtained while receiving MVC without change in background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | Change in Interleukin (IL)-6, Monocyte Chemoattractant Protein (MCP)-1, MCP-2, and Plasma CD40 Ligand (CD40L) | IL-6 | 0.7 pg/ml |
| Maraviroc | Change in Interleukin (IL)-6, Monocyte Chemoattractant Protein (MCP)-1, MCP-2, and Plasma CD40 Ligand (CD40L) | MCP-1 | 44.6 pg/ml |
| Maraviroc | Change in Interleukin (IL)-6, Monocyte Chemoattractant Protein (MCP)-1, MCP-2, and Plasma CD40 Ligand (CD40L) | MCP-2 | -1.4 pg/ml |
| Maraviroc | Change in Interleukin (IL)-6, Monocyte Chemoattractant Protein (MCP)-1, MCP-2, and Plasma CD40 Ligand (CD40L) | CD40L | -1.8 pg/ml |
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+
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
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with a week 36 result obtained while receiving background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | 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+ | naïve (%CD45RA+CCR7+) | 3.5 % of CD4+ T-cells |
| Maraviroc | 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+ | central memory (%CD45RA-CCR7+) | -1.4 % of CD4+ T-cells |
| Maraviroc | 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+ | effector memory (%CD45RA-CCR7-) | -3.7 % of CD4+ T-cells |
| Maraviroc | 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+ | effector (%CD45RA+CCR7-) | 0.1 % of CD4+ T-cells |
| Maraviroc | 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+ | %HLA-DR+CD38+ | -0.2 % of CD4+ T-cells |
| Maraviroc | 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+ | %CD38+ | 2.8 % of CD4+ T-cells |
| Maraviroc | 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+ | %Ki67+ | 0.1 % of CD4+ T-cells |
| Maraviroc | 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+ | %caspase3+ | 0.3 % of CD4+ T-cells |
| Maraviroc | 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+ | %Bcl-2- | -0.6 % of CD4+ T-cells |
| Maraviroc | 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+ | %CD57+ | -0.9 % of CD4+ T-cells |
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+
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
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with either a week 46 result or a week 48 result obtained while receiving background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | 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+ | naïve (%CD45RA+CCR7+) | 2.1 % of CD4+ T-cells |
| Maraviroc | 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+ | central memory (%CD45RA-CCR7+) | -3.1 % of CD4+ T-cells |
| Maraviroc | 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+ | effector memory (%CD45RA-CCR7-) | 0.4 % of CD4+ T-cells |
| Maraviroc | 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+ | effector (%CD45RA+CCR7-) | 1.2 % of CD4+ T-cells |
| Maraviroc | 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+ | %HLA-DR+CD38+ | 0.4 % of CD4+ T-cells |
| Maraviroc | 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+ | %CD38+ | 7.1 % of CD4+ T-cells |
| Maraviroc | 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+ | %Ki67+ | 0.1 % of CD4+ T-cells |
| Maraviroc | 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+ | %caspase3+ | 0.7 % of CD4+ T-cells |
| Maraviroc | 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+ | %Bcl-2- | -0.5 % of CD4+ T-cells |
| Maraviroc | 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+ | %CD57+ | -0.4 % of CD4+ T-cells |
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+
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
Population: As-treated: Only participants with either a week 22 result or a week 24 result obtained while receiving MVC without change in background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | 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+ | naïve (%CD45RA+CCR7+) | -1.3 % of CD4+ T-cells |
| Maraviroc | 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+ | central memory (%CD45RA-CCR7+) | -4.8 % of CD4+ T-cells |
| Maraviroc | 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+ | effector memory (%CD45RA-CCR7-) | 5.8 % of CD4+ T-cells |
| Maraviroc | 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+ | effector (%CD45RA+CCR7-) | 0.7 % of CD4+ T-cells |
| Maraviroc | 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+ | %HLA-DR+CD38+ | -1.3 % of CD4+ T-cells |
| Maraviroc | 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+ | %CD38+ | -14.8 % of CD4+ T-cells |
| Maraviroc | 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+ | %Ki67+ | -1.0 % of CD4+ T-cells |
| Maraviroc | 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+ | %caspase3+ | -1.1 % of CD4+ T-cells |
| Maraviroc | 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+ | %Bcl-2- | 0.7 % of CD4+ T-cells |
| Maraviroc | 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+ | %CD57+ | 1.8 % of CD4+ T-cells |
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+
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
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with either a week 46 result or a week 48 result obtained while receiving background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | 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+ | naïve (%CD45RA+CCR7+) | 1.1 % of CD8+ T-cells |
| Maraviroc | 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+ | central memory (%CD45RA-CCR7+) | -0.5 % of CD8+ T-cells |
| Maraviroc | 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+ | effector memory (%CD45RA-CCR7-) | -0.1 % of CD8+ T-cells |
| Maraviroc | 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+ | effector (%CD45RA+CCR7-) | 0.4 % of CD8+ T-cells |
| Maraviroc | 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+ | %HLA-DR+CD38+ | 0.1 % of CD8+ T-cells |
| Maraviroc | 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+ | %CD38+ | 4.2 % of CD8+ T-cells |
| Maraviroc | 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+ | %Ki67+ | 0.2 % of CD8+ T-cells |
| Maraviroc | 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+ | %caspase3+ | 0.5 % of CD8+ T-cells |
| Maraviroc | 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+ | %Bcl-2- | 0 % of CD8+ T-cells |
| Maraviroc | 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+ | %CD57+ | -1.4 % of CD8+ T-cells |
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+
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
Population: As-treated: Only participants with either a week 22 result or a week 24 result obtained while receiving MVC without change in background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | 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+ | naïve (%CD45RA+CCR7+) | -3.3 % of CD8+ T-cells |
| Maraviroc | 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+ | central memory (%CD45RA-CCR7+) | -1.0 % of CD8+ T-cells |
| Maraviroc | 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+ | effector memory (%CD45RA-CCR7-) | 2.5 % of CD8+ T-cells |
| Maraviroc | 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+ | effector (%CD45RA+CCR7-) | 2.0 % of CD8+ T-cells |
| Maraviroc | 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+ | %HLA-DR+CD38+ | -1.4 % of CD8+ T-cells |
| Maraviroc | 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+ | %CD38+ | -14.2 % of CD8+ T-cells |
| Maraviroc | 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+ | %Ki67+ | -0.1 % of CD8+ T-cells |
| Maraviroc | 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+ | %caspase3+ | -0.7 % of CD8+ T-cells |
| Maraviroc | 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+ | %Bcl-2- | 0.5 % of CD8+ T-cells |
| Maraviroc | 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+ | %CD57+ | 3.6 % of CD8+ T-cells |
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+
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
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with a week 36 result obtained while receiving background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | 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+ | %HLA-DR+CD38+ | -0.8 % of CD8+ T-cells |
| Maraviroc | 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+ | naïve (%CD45RA+CCR7+) | 2.4 % of CD8+ T-cells |
| Maraviroc | 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+ | central memory (%CD45RA-CCR7+) | -0.3 % of CD8+ T-cells |
| Maraviroc | 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+ | effector memory (%CD45RA-CCR7-) | -5.1 % of CD8+ T-cells |
| Maraviroc | 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+ | effector (%CD45RA+CCR7-) | 2.4 % of CD8+ T-cells |
| Maraviroc | 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+ | %CD38+ | -1.6 % of CD8+ T-cells |
| Maraviroc | 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+ | %Ki67+ | 0.1 % of CD8+ T-cells |
| Maraviroc | 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+ | %caspase3+ | 0.2 % of CD8+ T-cells |
| Maraviroc | 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+ | %Bcl-2- | -0.3 % of CD8+ T-cells |
| Maraviroc | 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+ | %CD57+ | -2.8 % of CD8+ T-cells |
Secondary
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.
Time frame: From week 24 to week 48
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with either a week 46 result or a week 48 result obtained while receiving background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in Soluble CD14 | -0.16 mcg/ml |
Secondary
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.
Time frame: From baseline to week 24
Population: As-treated: Only participants with either a week 22 result or a week 24 result obtained while receiving MVC without change in background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in Soluble CD14 | -0.03 mcg/ml |
Secondary
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.
Time frame: From week 24 to week 36
Population: As-treated: Only participants that were included in the primary week 24 analysis, i.e. change from baseline to week 24, and with a week 36 result obtained while receiving background regimen were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change in Soluble CD14 | -0.17 mcg/ml |
Secondary
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.
Time frame: At weeks 4, 12, and 24
Population: As-treated: Participants who initiated treatment were included. Follow-up while receiving MVC without change in background regimen were included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Maraviroc | Drug Adherence Assessed as Number of Missed Doses Over a 4-day Recall | Week 4 (N=30) | 0 doses missed |
| Maraviroc | Drug Adherence Assessed as Number of Missed Doses Over a 4-day Recall | Week 12 (N=28) | 0 doses missed |
| Maraviroc | Drug Adherence Assessed as Number of Missed Doses Over a 4-day Recall | Week 24 (N=27) | 0 doses missed |
Secondary
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.
Time frame: From baseline through week 24
Population: As-treated: Participants who initiated treatment were included. Follow-up while receiving MVC without change in background regimen were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Number of Subjects Who Experience a Grade 2, 3 or 4 Signs and Symptoms, Grade 3 or 4 Laboratory Abnormalities, or Death. | grade>=2 signs/symptoms or grade>=3 lab abnorm. | 15 participants |
| Maraviroc | Number of Subjects Who Experience a Grade 2, 3 or 4 Signs and Symptoms, Grade 3 or 4 Laboratory Abnormalities, or Death. | deaths | 0 participants |
Secondary
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.
Time frame: From baseline to week 24
Population: As-treated: Only participants with either a week 22 CD4+ T-cell count or a week 24 CD4+ T-cell count obtained while receiving MVC without change in background regimen were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Maraviroc | Proportion of Participants Achieving a 50-cell Increase in CD4+ T-cell Count | 0.06 proportion of participants |
Secondary
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.
Time frame: At weeks -1 (pre-entry), 0 (entry), 12, 22, 24, and 36
Population: As-treated: Participants who initiated treatment were included. Through week 24, follow-up while receiving MVC without change in background regimen were included. For week 36, only results obtained while receiving background regimen were included. One subject who had a large rise (blip) in viral load at week 24 was excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Maraviroc | Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA) | Week -1 (N=31) | 0.35 proportion of participants |
| Maraviroc | Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA) | Week 0 (N=31) | 0.32 proportion of participants |
| Maraviroc | Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA) | Week 12 (N=30) | 0.43 proportion of participants |
| Maraviroc | Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA) | Week 22 (N=31) | 0.29 proportion of participants |
| Maraviroc | Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA) | Week 24 (N=29) | 0.48 proportion of participants |
| Maraviroc | Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA) | Week 36 (N=30) | 0.43 proportion of participants |
Secondary
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.
Time frame: From baseline through week 24
Population: As-treated: Participants with CD4 percentage available at least through visit week 22 while receiving MVC without change in background regimen were included. Four of these subjects did not have pre-treatment (from at least 48 weeks prior to study entry) CD4 percentage results available.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Maraviroc | Within-subject CD4 Percentage Slopes | -0.3 % of total lymphocytes/year |
Secondary
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.
Time frame: From baseline through week 24
Population: As-treated: Participants with CD4+ T-cell counts available at least through visit week 22 while receiving MVC without change in background regimen were included.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Maraviroc | Within-subject CD4+ T-cell Count Slopes | 24.7 cells/mm^3/year |