Maraviroc Intensification and Peripheral Blood Monocyte HIV DNA Levels

Pilot Study of the Effect of Maraviroc Intensification on Peripheral Blood Monocyte HIV DNA Levels When Given to HIV-Infected Subjects Stable on Highly Active Antiretroviral Therapy With Undetectable Plasma HIV RNA

High levels of HIV infection within blood monocyte/macrophages (a type of white cells in the bloodstream) increases risk of dementia in HIV-infected individuals. Maraviroc (Selzentry) is a HIV medication that works by blocking the entry of HIV in cells including monocytes/macrophages that use a receptor called CCR5. The study hypothesis is that the addition of Maraviroc to a HIV antiretroviral regimen in HIV-infected individuals with high levels of HIV-infected monocyte/macrophages will lead to a decrease in the levels of infected monocyte/macrophages and to decrease in brain inflammation as studied by magnetic resonance spectroscopy (MRS, a form of MRI study).

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: maraviroc (Selzentry)

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Hawaii
    • Honolulu, Hawaii, United States, 96816
      • Hawaii Center for AIDS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV-1 infection as documented by ELISA and confirmed by either Western blot, HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA by RT-PCR or bDNA at any time prior to study entry.
• Receipt of ARV medication uninterrupted for > 1 year leading up to the screening period with demonstrated HIV RNA < 50 copies/ml for a period of 1 year."
• Willingness for both males and females of childbearing potential to utilize 2 effective contraception methods (2 separate forms, one of which must be an effective barrier method), be non-heterosexually active or have a an exclusive vasectomized partner from screening throughout the duration of the study treatment and for 30 days following the last dose of study drugs.
• Age >18 years.
• Ability and willingness to provide written informed consent

• The following laboratory parameters documented within 30 days prior to study entry:

  • Hemoglobin >8.0
  • Absolute neutrophil count >500
  • Platelet count >40,000
  • AST (SGOT) and ALT (SGPT) <5 x ULN
  • Creatinine <1.5 x ULN
  • Lipase <2.0 x ULN
  • Estimated creatinine clearance > 60 mL/min.
• HIV DNA within peripheral blood mononuclear cells > 100 copies/mL
• Not currently receiving Maraviroc as part of ARV regimen

Exclusion Criteria:

• Past or present HIV opportunistic infection of the brain, learning disability, head injury with prolonged loss of consciousness or cognitive sequelae, or other non-HIV risk factor that may impact cognitive performance.
• Any factor that precludes MRI scan including presence of metal or exposure to metal work (e.g., metal grinder/worker) and claustrophobia
• History of seizure disorder
• History of myocardial infarction, angina, congestive heart failure, peripheral vascular disease, angioplasty or cardiac surgery
• Current malignancy or history of past malignancies excluding basal cell CA
• Any immunomodulator, HIV vaccine, or investigational therapy within 30 days of study entry.
• Any vaccination within 30 days of study entry.
• Requirement for acute therapy for other AIDS-defining illness or other serious medical illnesses (in the opinion of the site investigator) within 14 days prior to study entry.
• Other chronic illnesses including diabetes, autoimmune diseases, and endocrinopathies, except subjects on stable physiologic replacement therapy for low testosterone or thyroid levels
• Known hypersensitivity to Maraviroc
• Any condition which, in the opinion of the investigator, would compromise the subject's ability to participate in the study
• Current active substance or alcohol dependence
• Pregnancy or breast-feeding, intent to become pregnant during the course of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Maraviroc	Drug: maraviroc (Selzentry); dosage varies with other medications being taken; will follow package insert guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to 24 Weeks in HIV DNA (Log-10 Copies/10^6 Cells) as Measured by HIV DNA Within CD14+ Peripheral Blood Mononuclear Cells	Week 24 minus baseline	Baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to 24 Weeks in Neuropsychological Performance As Measured by Age- and Education-Adjusted Z-Scores	The Z-score represents the number of standard deviations away from the mean, with positive Z-scores representing better neuropsychological performance and negative Z-scores representing poorer neuropsychological performance. Z-scores have been adjusted based on age- and education-matched norms.	Baseline to 24 Weeks

Collaborators and Investigators

• Sponsor: University of Hawaii
• Collaborators: Pfizer
• Investigators: Principal Investigator: Cecilia M Shikuma, M.D., University of Hawaii at Manoa

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: September 29, 2009
• First Submitted That Met QC Criteria: September 30, 2009
• First Posted (Estimate): October 1, 2009

Study Record Updates

• Last Update Posted (Actual): March 22, 2017
• Last Update Submitted That Met QC Criteria: February 1, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: dementia; HIV; treatment experienced; High HIV DNA within CD14+ PBMCs
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc
• Other Study ID Numbers: H005