Maraviroc Intensification and Peripheral Blood Monocyte HIV DNA Levels

Phase 2

Completed

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).

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Maraviroc	maraviroc (Selzentry)	-

Primary Outcome Measures

Name	Time	Method
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	Baseline to 24 weeks	Week 24 minus baseline

Secondary Outcome Measures

Name	Time	Method
Change From Baseline to 24 Weeks in Neuropsychological Performance As Measured by Age- and Education-Adjusted Z-Scores	Baseline to 24 Weeks	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.