Cardiovascular Disease, HIV Infection, HIV Infections, Inflammation
Conditions
Keywords
Treatment Experienced, CCR5 receptor, maraviroc
Brief summary
The purpose of this study is to determine the potentially beneficial aspects of CCR5 inhibition on inflammation and endothelial function as measured by brachial artery reactivity in antiretroviral treated HIV patients with an undetectable viral load.
Interventions
DRUGMaraviroc
For subjects assigned to the maraviroc group, they will receive maraviroc at 300mg by mouth twice daily for 24 weeks in addition to taking their current anti-HIV medications. For subjects on ritonavir, the dose will be reduced to 150mg by mouth twice daily for 24 weeks.
DRUGplacebo
For subjects assigned to the placebo group, they will receive a matching placebo pill 300mg to be taken by mouth twice daily for 24 weeks in addition to taking their current anti-HIV medications.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Pfizer
University of California, San Francisco
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Stable antiretroviral therapy for at least 12 months 2. All plasma HIV RNA levels within the past year must be below level of detection (\< 50 copies RNA/mL), although isolated single values \> 50 but \< 200 copies will be allowed. 3. Screening plasma HIV RNA levels \< 50 copies RNA/mL 4. \>90% adherence to therapy within the preceding 30 days, as determined by self-report 5. Females of childbearing potential must have a negative serum pregnancy test at screening and agree to use a double-barrier method of contraception throughout the study period.
Exclusion criteria
1. Ongoing or prior use of any integrase inhibitor or R5 inhibitor. 2. Patients who plan to modify existing antiretroviral therapy in the next 24 weeks for any reason 3. Serious illness requiring hospitalization or parental antibiotics within preceding 3 months 4. Concurrent or recent exposure to any immunomodulatory drugs 5. Advanced liver disease or active hepatitis B or C 6. Patients with systolic blood pressure \<100/70 7. Starting or stopping statin therapy during the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in FMD | Baseline, 24 weeks | endothelial function as assessed by measured flow-mediated vasodilation (FMD) of the brachial artery |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Maraviroc maraviroc at 300mg by mouth twice daily for 24 weeks in addition to current anti-HIV medication regimen. For subjects on ritonavir, the dose of maraviroc was 150mg by mouth twice daily. | 26 |
| Placebo matching placebo pill 300mg by mouth twice daily for 24 weeks in addition to current anti-HIV medication regimen. | 26 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Maraviroc | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 52 years | 52 years | 52 years |
| Region of Enrollment United States | 26 participants | 26 participants | 52 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 25 Participants | 26 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 26 | 0 / 26 |
| serious Total, serious adverse events | 1 / 26 | 0 / 26 |
Outcome results
Primary
Percent Change in FMD
endothelial function as assessed by measured flow-mediated vasodilation (FMD) of the brachial artery
Time frame: Baseline, 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Maraviroc | Percent Change in FMD | 0.57 percent change in FMD | Standard Deviation 2.1 |
| Placebo | Percent Change in FMD | -0.05 percent change in FMD | Standard Deviation 2.1 |
Comparison: within-arm, pre-post change in FMDp-value: 0.17t-test, 2 sided
Comparison: within-arm, pre-post change in FMDp-value: 0.9t-test, 2 sided