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”

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.

Study Type: Interventional

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

Study Primary Completion Date: September 2010

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.

Intervention(s) in this Clinical Trial

• 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, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • 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.

Primary Measures

• Increase in CD4 count
  • Time Frame: Throughout study
    Safety Issue?: No

Secondary Measures

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

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 16 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Overall Clinical Trial Officials and Contacts

Timothy J. Wilkin, MD, MPH Study Chair Cornell Clinical Research Site  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00709111

Study ID Number: ACTG A5256

ClinicalTrials.gov Identifier: NCT00709111

Health Authority: United States: Federal Government

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