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

Condition(s) targeted: HIV Infections

Intervention: Maraviroc (Drug)

Phase: N/A

Status: Recruiting

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

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

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.

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

Primary outcome: Increase in CD4 count

Secondary outcome:

Persistence of CD4 count increase after discontinuation of MVC

Safety and tolerability of MVC in subjects on ART with suboptimal CD4 response

Mechanism by which MVC influences CD4 count measured by a set of immunologic markers

Effect of MVC on gut microbial translocation

Effect of MVC on low-level HIV-1 viremia

Effect of MVC on inflammatory markers

Adherence to study medications and relationship between adherence and study outcome

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.

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

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

Ucsf Aids Crs, San Francisco, California 94110, United States; Not yet recruiting
Michele Downing, RN, Phone: 415-476-4082, Ext: 354, Email: mdowning@php.ucsf.edu
Diane V. Havlir, MD, Principal Investigator

UCLA CARE Center CRS, Los Angeles, California 90035, United States; Recruiting
Maricela Gonzalez, Phone: 310-557-3798, Email: mmgonzalez@mednet.ucla.edu
Judith S. Currier, MD, MSc, Principal Investigator

Georgetown University CRS (GU CRS), Washington, District of Columbia 20007, United States; Recruiting
Abimael Lopez, Phone: 202-687-7387, Email: al374@georgetown.edu
Princy N. Kumar, MD, Principal Investigator

Univ. of Miami AIDS CRS, Miami, Florida 33136, United States; Recruiting
Leslie Thompson, RN, BSN, Phone: 305-243-3838, Email: lthomps@gate.net
Margaret A. Fischl, MD, Principal Investigator

The Ponce de Leon Ctr. CRS, Atlanta, Georgia 30308, United States; Recruiting
Ericka Patrick, Phone: 404-616-6313, Email: erpatri@emory.edu
Carlos del Rio, MD, Principal Investigator

Northwestern University CRS, Chicago, Illinois 60611, United States; Not yet recruiting
Baiba Berzins, MPH, Phone: 312-695-4994, Email: Baiba@northwestern.edu
Babafemi O. Taiwo, MD, Principal Investigator

Massachusetts General Hospital ACTG CRS, Boston, Massachusetts 02114, United States; Recruiting
Teri Flynn, RN, MSN, ANP, Phone: 1-617-724-0072, Email: tflynn@partners.org
Rajesh T. Gandhi, MD, Principal Investigator

Brigham and Women's Hosp. ACTG CRS, Boston, Massachusetts 02115, United States; Recruiting
Jon Gothing, RN, Phone: 617-732-5635, Email: jgothing@partners.org
Paul E. Sax, MD, Principal Investigator

Duke Univ. Med. Ctr. Adult CRS, Durham, North Carolina 27710, United States; Not yet recruiting
Sara Patillo, MHS, CCRP, Phone: 919-684-8216, Email: sara.patillo@duke.edu
Nathan M. Thielman, MD, MPH, Principal Investigator

Houston AIDS Research Team CRS, Houston, Texas 77030, United States; Not yet recruiting
Hilda Cuervo, Phone: 713-500-6751, Email: Hilda.cuervo@uth.tmc.edu
Roberto C. Arduino, MD, Principal Investigator

Click here for more information about maraviroc

Related 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.

Starting date: September 2009
Last updated: February 19, 2009