Safety and Effectiveness of Addition of Maraviroc to ART Regimens in HIV-Infected Adults With Suboptimal CD4 T-Cell Count Recovery Despite Sustained Virologic Suppression - Full Text View

Sponsor:	National Institute of Allergy and Infectious Diseases (NIAID)
Collaborator:	Adult AIDS Clinical Trials Group
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00709111

Purpose

Some HIV-infected individuals with low viral load on antiretroviral therapy (ART) do not have increased CD4 counts and remains at risk for clinical progression of HIV. The purpose of this study is to assess whether adding maraviroc (MVC) to a stable ART regimen will result in an improved immune response in individuals with a limited CD4 response despite sustained virologic suppression.

Condition	Intervention	Phase
HIV Infections	Drug: Maraviroc	Phase 0

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
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

Resource links provided by NLM:

MedlinePlus related topics: AIDS

Drug Information available for: Maraviroc

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Increase in CD4 count [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Persistence of CD4 count increase after discontinuation of MVC [ Time Frame: From Weeks 24 to 48 ] [ Designated as safety issue: No ]
Safety and tolerability of MVC in subjects on ART with suboptimal CD4 response [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Mechanism by which MVC influences CD4 count measured by a set of immunologic markers [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Effect of MVC on gut microbial translocation [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Effect of MVC on low-level HIV-1 viremia [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Effect of MVC on inflammatory markers [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Adherence to study medications and relationship between adherence and study outcome [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	32
Study Start Date:	September 2009
Estimated Primary Completion Date:	September 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Maraviroc (MVC) will be taken orally twice daily for 24 weeks. Dosage is dependent on the pharmacokinetic interaction with participant's current ART and non-ART drug regimen.	Drug: Maraviroc 150 mg taken orally twice daily for participants already receiving the following: potent CYP3A inhibitors (e.g., all protease inhibitors, with or without ritonavir, with or without NNRTI, except tipranavir/ritonavir (TPV/RTV); delavirdine, itraconazole, ketoconazole, clarithromycin, nefazadone, telithromycin) 300 mg taken orally twice daily for participants already receiving the following: TPV/RTV and regimens without CYP3A inducers or inhibitors (including NRTI-only regimen, nevirapine, raltegravir, enfuvirtide) 600 mg taken orally twice daily for participants already receiving the following: potent CYP3A inducers without a strong CYP3A inhibitor (e.g., efavirenz, etravirine, carbamazepine, phenobarbital, and phenytoin)

Arms

Assigned Interventions

1: Experimental

Maraviroc (MVC) will be taken orally twice daily for 24 weeks. Dosage is dependent on the pharmacokinetic interaction with participant's current ART and non-ART drug regimen.

Drug: Maraviroc

150 mg taken orally twice daily for participants already receiving the following: potent CYP3A inhibitors (e.g., all protease inhibitors, with or without ritonavir, with or without NNRTI, except tipranavir/ritonavir (TPV/RTV); delavirdine, itraconazole, ketoconazole, clarithromycin, nefazadone, telithromycin)

300 mg taken orally twice daily for participants already receiving the following: TPV/RTV and regimens without CYP3A inducers or inhibitors (including NRTI-only regimen, nevirapine, raltegravir, enfuvirtide)

600 mg taken orally twice daily for participants already receiving the following: potent CYP3A inducers without a strong CYP3A inhibitor (e.g., efavirenz, etravirine, carbamazepine, phenobarbital, and phenytoin)

Detailed Description:

The majority of HIV-infected individuals with virologic suppression on antiretroviral therapy (ART) have a significant increase in CD4 count over the first year. However, a portion of these individuals show a suboptimal immune response and remain at an elevated risk for clinical progression. The primary purpose of this study is to determine the effectiveness and safety of the addition of maraviroc (MVC) to stable treatment regimens in individuals with suboptimal immune response despite sustained virologic suppression.

This study will last approximately 48 weeks. All participants will add MVC to their current antiretroviral drug regimen for 24 weeks. Dosage of MVC will depend on the regimen of each participant. At Week 24, participants will discontinue MVC and be followed for an additional 24 weeks.

All participants will have study visits at study entry and Weeks 4, 8, 12, 16, 22, 24, 36, 46, and 48. A clinical assessment and blood collection will occur at all visits. A questionnaire will take place at select visits. For women, a pregnancy test will occur at study entry and Week 24. MVC will be distributed at study entry and Weeks 8 and 16. Other ART will not be supplied by the study.

Eligibility

Ages Eligible for Study:	16 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-1 infection
Taking 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
CD4 count less than 250 within 60 days prior to study entry
Stable CD4 count for at least 48 weeks prior to study entry. More information on this criterion can be found in the protocol.
Documentation of CD4 count obtained within 14 days prior to study entry
Documentation of viral load less than the limit of detection. All viral load measurements within 48 weeks of study entry must be less than the limit of detection. More information on this criterion can be found in the protocol.
Confirmation of the availability of stored plasma sample obtained at the pre-entry visit
Confirmation that advanced lymphocyte flow cytometry has been performed within14 days prior to study entry
Females of reproductive potential. More information on this criterion can be found in the protocol.
Agree to use at least two forms of contraception while using study treatment and for the 6 weeks after stopping study treatment

Exclusion Criteria:

Unstable clinical condition. More information on this criterion can be found in the protocol.
Using immunomodulators within 12 months prior to study entry. More information on this criterion can be found in the protocol.
Acute AIDS-defining illness within 60 days prior to study entry
Known allergy/sensitivity or hypersensitivity to 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 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 counts within 6 months prior to study entry
Certain abnormal laboratory values. More information on this criterion can be found in the protocol.
Pregnant or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00709111

Locations

United States, California
Ucsf Aids Crs	Not yet recruiting
San Francisco, California, United States, 94110
Contact: Michele Downing, RN 415-476-4082 ext 354 mdowning@php.ucsf.edu
Principal Investigator: Diane V. Havlir, MD
UCLA CARE Center CRS	Recruiting
Los Angeles, California, United States, 90035
Contact: Maricela Gonzalez 310-557-3798 mmgonzalez@mednet.ucla.edu
Principal Investigator: Judith S. Currier, MD, MSc
United States, District of Columbia
Georgetown University CRS (GU CRS)	Recruiting
Washington, District of Columbia, United States, 20007
Contact: Abimael Lopez 202-687-7387 al374@georgetown.edu
Principal Investigator: Princy N. Kumar, MD
United States, Florida
Univ. of Miami AIDS CRS	Recruiting
Miami, Florida, United States, 33136
Contact: Leslie Thompson, RN, BSN 305-243-3838 lthomps@gate.net
Principal Investigator: Margaret A. Fischl, MD
United States, Georgia
The Ponce de Leon Ctr. CRS	Recruiting
Atlanta, Georgia, United States, 30308
Contact: Ericka Patrick 404-616-6313 erpatri@emory.edu
Principal Investigator: Carlos del Rio, MD
United States, Illinois
Northwestern University CRS	Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Baiba Berzins, MPH 312-695-4994 Baiba@northwestern.edu
Principal Investigator: Babafemi O. Taiwo, MD
United States, Massachusetts
Massachusetts General Hospital ACTG CRS	Recruiting
Boston, Massachusetts, United States, 02114
Contact: Teri Flynn, RN, MSN, ANP 1-617-724-0072 tflynn@partners.org
Principal Investigator: Rajesh T. Gandhi, MD
Brigham and Women's Hosp. ACTG CRS	Recruiting
Boston, Massachusetts, United States, 02115
Contact: Jon Gothing, RN 617-732-5635 jgothing@partners.org
Principal Investigator: Paul E. Sax, MD
United States, North Carolina
Duke Univ. Med. Ctr. Adult CRS	Not yet recruiting
Durham, North Carolina, United States, 27710
Contact: Sara Patillo, MHS, CCRP 919-684-8216 sara.patillo@duke.edu
Principal Investigator: Nathan M. Thielman, MD, MPH
United States, Texas
Houston AIDS Research Team CRS	Not yet recruiting
Houston, Texas, United States, 77030
Contact: Hilda Cuervo 713-500-6751 Hilda.cuervo@uth.tmc.edu
Principal Investigator: Roberto C. Arduino, MD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Adult AIDS Clinical Trials Group

Investigators

Study Chair:	Timothy J. Wilkin, MD, MPH	Cornell Clinical Research Site
Study Chair:	Roy Gulick, MD, MPH	Cornell HIV Clinical Trials Unit

More Information

Additional Information:

Click here for more information about maraviroc This link exits the ClinicalTrials.gov site

Publications:

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

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5256, A5256
Study First Received:	July 1, 2008
Last Updated:	February 19, 2009
ClinicalTrials.gov Identifier:	NCT00709111 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Treatment Experienced

Additional relevant MeSH terms:

Virus Diseases
Sexually Transmitted Diseases, Viral
RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Infection
Retroviridae Infections
Immunologic Deficiency Syndromes

ClinicalTrials.gov processed this record on February 08, 2010