Clinical trial NCT00987948: Maraviroc Intensification and Peripheral Blood Monocyte HIV DNA Levels
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Keywords: HIV
dementia
High HIV DNA within CD14+ PBMCs
treatment experienced
Lead sponsor: University of Hawaii
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2009-10-01
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: Baseline to 24 weeks
Secondary outcomes:
measure: Change From Baseline to 24 Weeks in Neuropsychological Performance As Measured by Age- and Education-Adjusted Z-Scores
timeFrame: Baseline to 24 Weeks
Other outcomes:
Locations:
city: Honolulu
country: United States
facility: Hawaii Center for AIDS
state: Hawaii
Study officials:
affiliation: University of Hawaii at Manoa
name: Cecilia M Shikuma, M.D.
role: PRINCIPAL_INVESTIGATOR
References: