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

NCT ID: NCT00709111

Last Updated: 2018-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-31
• Study Completion Date: 2010-04-30

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.

Conditions

HIV Infections

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Maraviroc

Intervention Type: DRUG

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.

Interventions

Maraviroc

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.

Intervention Type: DRUG

Other Intervention Names

MVC; Selzentry

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

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Timothy J. Wilkin, MD, MPH

Role: STUDY_CHAIR

Cornell Clinical Research Site

Roy Gulick, MD, MPH

Role: STUDY_CHAIR

Cornell HIV Clinical Trials Unit

Locations

Alabama Therapeutics CRS (5801)

Birmingham, Alabama, United States

UCLA CARE Center CRS (601)

Los Angeles, California, United States

Stanford CRS (501)

Palo Alto, California, United States

Ucsd, Avrc Crs (701)

San Diego, California, United States

Ucsf Aids Crs (801)

San Francisco, California, United States

Georgetown University CRS (GU CRS) (1008)

Washington D.C., District of Columbia, United States

Univ. of Miami AIDS CRS (901)

Miami, Florida, United States

The Ponce de Leon Ctr. CRS (5802)

Atlanta, Georgia, United States

Northwestern University CRS (2701)

Chicago, Illinois, United States

IHV Baltimore Treatment CRS (4651)

Baltimore, Maryland, United States

Johns Hopkins Adult AIDS CRS (201)

Baltimore, Maryland, United States

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, United States

Brigham and Women's Hosp. ACTG CRS (107)

Boston, Massachusetts, United States

Boston Medical Center ACTG CRS (104)

Boston, Massachusetts, United States

Washington University CRS (2101)

St Louis, Missouri, United States

Cornell CRS (7804)

New York, New York, United States

NY Univ. HIV/AIDS CRS (401)

New York, New York, United States

AIDS Care CRS (1108)

Rochester, New York, United States

Univ. of Rochester ACTG CRS (1101)

Rochester, New York, United States

Unc Aids Crs (3201)

Chapel Hill, North Carolina, United States

Duke Univ. Med. Ctr. Adult CRS (1601)

Durham, North Carolina, United States

Univ. of Cincinnati CRS (2401)

Cincinnati, Ohio, United States

MetroHealth CRS (2503)

Cleveland, Ohio, United States

The Ohio State Univ. AIDS CRS (2301)

Columbus, Ohio, United States

Hosp. of the Univ. of Pennsylvania CRS (6201)

Philadelphia, Pennsylvania, United States

Pittsburgh CRS (1001)

Pittsburgh, Pennsylvania, United States

Vanderbilt Therapeutics CRS (3652)

Nashville, Tennessee, United States

Peabody Health Ctr. CRS (31443)

Dallas, Texas, United States

Houston AIDS Research Team CRS (31473)

Houston, Texas, United States

Countries

United States

References

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

Reference Type: BACKGROUND

PMID: 18174962 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18532888 (View on PubMed)

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: RESULT

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.

Reference Type: DERIVED

PMID: 22740718 (View on PubMed)

Other Identifiers

1U01AI068636

Identifier Type: NIH

Identifier Source: secondary_id

View Link

ACTG A5256

Identifier Type: -

Identifier Source: org_study_id