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

Information source: AIDS Clinical Trials Group
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: HIV Infections

Intervention: Maraviroc (Drug)

Phase: N/A

Status: Completed

Sponsored by: AIDS Clinical Trials Group

Official(s) and/or principal investigator(s):
Timothy J. Wilkin, MD, MPH, Study Chair, Affiliation: Cornell Clinical Research Site
Roy Gulick, MD, MPH, Study Chair, Affiliation: Cornell HIV Clinical Trials Unit

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.

Clinical Details

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 design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Change in CD4+ T-cell Count

Secondary outcome:

Proportion of Participants Achieving a 50-cell Increase in CD4+ T-cell Count

Within-subject CD4+ T-cell Count Slopes

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

Change in CD4+ T-cell Count

Change in CD4+ T-cell Count

Change in CD4 Percentage

Within-subject CD4 Percentage Slopes

Change From Within-subject Pre-treatment CD4 Percentage Slopes to Corresponding Within-subject CD4 Percentage Slopes From Baseline Through Week 24

Change in CD4 Percentage

Change in CD4 Percentage

Number of Subjects Who Experience a Grade 2, 3 or 4 Signs and Symptoms, Grade 3 or 4 Laboratory Abnormalities, or Death.

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 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 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 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 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 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 in Soluble CD14

Change in Soluble CD14

Change in Soluble CD14

Change in High Sensitivity C-reactive Protein (Hs-CRP)

Change in Interleukin (IL)-6, Monocyte Chemoattractant Protein (MCP)-1, MCP-2, and Plasma CD40 Ligand (CD40L)

Change in Intercellular Cell Adhesion Molecule (ICAM)-1, Plasma P-selectin, Soluble TNFRII (sTNFRII), and Matrix Metalloproteinase (MMP)-9

Change in D-dimer

Change in Hs-CRP

Change in IL-6, MCP-1, MCP-2, and Plasma CD40L

Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9

Change in D-dimer

Change in Hs-CRP

Change in IL-6, MCP-1, MCP-2, and Plasma CD40L

Change in ICAM-1, Plasma P-selectin, sTNFRII, and MMP-9

Change in D-dimer

Proportion of Participants With Detectable HIV-1 Viremia as Measured by Single Copy Assay (SCA)

Drug Adherence Assessed as Number of Missed Doses Over a 4-day Recall

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.

Eligibility

Minimum age: 16 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Alabama Therapeutics CRS (5801), Birmingham, Alabama 35294, United States

UCLA CARE Center CRS (601), Los Angeles, California 90035, United States

Stanford CRS (501), Palo Alto, California 94304, United States

Ucsd, Avrc Crs (701), San Diego, California 92103, United States

Ucsf Aids Crs (801), San Francisco, California 94110, United States

Georgetown University CRS (GU CRS) (1008), Washington, District of Columbia 20007, United States

Univ. of Miami AIDS CRS (901), Miami, Florida 33136, United States

The Ponce de Leon Ctr. CRS (5802), Atlanta, Georgia 30308, United States

Northwestern University CRS (2701), Chicago, Illinois 60611, United States

IHV Baltimore Treatment CRS (4651), Baltimore, Maryland 21201, United States

Johns Hopkins Adult AIDS CRS (201), Baltimore, Maryland 21205, United States

Boston Medical Center ACTG CRS (104), Boston, Massachusetts 02118, United States

Brigham and Women's Hosp. ACTG CRS (107), Boston, Massachusetts 02115, United States

Massachusetts General Hospital ACTG CRS (101), Boston, Massachusetts 02114, United States

Washington University CRS (2101), St. Louis, Missouri 63110, United States

Cornell CRS (7804), New York, New York 10011, United States

NY Univ. HIV/AIDS CRS (401), New York, New York 10016, United States

AIDS Care CRS (1108), Rochester, New York 14642, United States

Univ. of Rochester ACTG CRS (1101), Rochester, New York 14642, United States

Unc Aids Crs (3201), Chapel Hill, North Carolina 27516, United States

Duke Univ. Med. Ctr. Adult CRS (1601), Durham, North Carolina 27710, United States

Univ. of Cincinnati CRS (2401), Cincinnati, Ohio 45267, United States

MetroHealth CRS (2503), Cleveland, Ohio 44109, United States

The Ohio State Univ. AIDS CRS (2301), Columbus, Ohio 43210, United States

Hosp. of the Univ. of Pennsylvania CRS (6201), Philadelphia, Pennsylvania 19104, United States

Pittsburgh CRS (1001), Pittsburgh, Pennsylvania 15213, United States

Vanderbilt Therapeutics CRS (3652), Nashville, Tennessee 37204, United States

Peabody Health Ctr. CRS (31443), Dallas, Texas 75215, United States

Houston AIDS Research Team CRS (31473), Houston, Texas 77030, United States

Additional Information

Click here for more information about maraviroc

Related publications:

Fadel H, Temesgen Z. Maraviroc. Drugs Today (Barc). 2007 Nov;43(11):749-58. doi: 10.1358/dot.2007.43.11.1131763. Review.

MacArthur RD, Novak RM. Reviews of anti-infective agents: maraviroc: the first of a new class of antiretroviral agents. Clin Infect Dis. 2008 Jul 15;47(2):236-41. doi: 10.1086/589289. Review.

Starting date: January 2009
Last updated: January 23, 2012

Page last updated: August 23, 2015

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