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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00709111
• Date of registration: 01/07/2008
• Prospective Registration: Yes
• Primary sponsor: AIDS Clinical Trials Group
• Public title: Adding Maraviroc to Antiretroviral Therapy for Suboptimal CD4 T-Cell Recovery Despite Sustained Virologic Suppression
• Scientific title: A Pilot Trial of Maraviroc for Treatment of Subjects on Antiretroviral Therapy With Suboptimal CD4 T-cell Count Recovery Despite Sustained Virologic Suppression
• Date of first enrolment: January 2009
• Target sample size: 34
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00709111
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: N/A

Countries of recruitment

United States

Contacts

• Name: Timothy J. Wilkin, MD, MPH
• Affiliation: Cornell Clinical Research Site

• Name: Roy Gulick, MD, MPH
• Affiliation: Cornell HIV Clinical Trials Unit

Key inclusion & exclusion 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



Age minimum: 16 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

HIV Infections

Intervention(s)

Drug: Maraviroc

Primary Outcome(s)

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

Secondary Outcome(s)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary ID(s)

ACTG A5256

1U01AI068636

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Institute of Allergy and Infectious Diseases (NIAID)

Results

• Results available: Yes
• Date Posted: 24/02/2012
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00709111