HIV Infections
Conditions
Keywords
HIV, dementia, High HIV DNA within CD14+ PBMCs, treatment experienced
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).
Interventions
DRUGmaraviroc (Selzentry)
dosage varies with other medications being taken; will follow package insert guidelines
Sponsors
Pfizer
University of Hawaii
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc maraviroc (Selzentry): dosage varies with other medications being taken; will follow package insert guidelines | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Maraviroc |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 11 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 1 / 15 |
Outcome results
Primary
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
Time frame: Baseline to 24 weeks
Population: Outcome measure in the 12 patients who completed the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | 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 | 0.58 Log-10 copies/10^6 cells |
Secondary
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.
Time frame: Baseline to 24 Weeks
Population: 6 of 12 patients who completed the study who had mild to moderate cognitive impairment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Maraviroc | Change From Baseline to 24 Weeks in Neuropsychological Performance As Measured by Age- and Education-Adjusted Z-Scores | 0.57 Z-score |