HIV
Conditions
Keywords
HIV, Lymphoid fibrosis
Brief summary
The investigators propose a proof-of-concept, pathogenesis-oriented, randomized, placebo-controlled pilot study to assess whether the addition of an angiotensin converting enzyme (ACE) inhibitor to standard Highly Active Antiretroviral Therapy (HAART) reverses lymphoid fibrosis, and whether this leads to more effective HIV-specific host immune responses and an accelerated clearance of the latent reservoir.
Interventions
DRUGLisinopril
Lisinopril 20mg QD x 24 weeks
DRUGPlacebo
Placebo QD x24wks
Sponsors
amfAR, The Foundation for AIDS Research
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
include: * Stable HAART with maintenance of plasma HIV RNA levels below level of detection (\< 40-75 copies/mL) for ≥ 12 months * \> 90% adherence to HAART within preceding 30 days
Exclusion criteria
include: * Screening systolic blood pressure \< 110mm Hg or diastolic blood pressure \< 60mm Hg * Current use of any ACE inhibitor, angiotensin receptor blocker, or aldosterone antagonist * Known diabetes mellitus or cardiovascular/kidney/collagen vascular disease * Pregnant/breastfeeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HIV RNA (Copies/Million Rectal Cells) | 22 weeks | Change in HIV RNA measured in GALT (gut-associated lymphoid tissue) from baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in HIV DNA (Copies/Million Rectal Cells) | 22 weeks | Change in HIV DNA measured in GALT (gut-associated lymphoid tissue) from baseline |
Countries
United States
Participant flow
Pre-assignment details
The trial over enrolled by one individual as one participant discontinued the study after enrollment due to an adverse event.
Participants by arm
| Arm | Count |
|---|---|
| ACE Inhibitor Active group
Lisinopril: Lisinopril 20mg Daily x 24 weeks | 16 |
| Placebo Placebo group
Placebo: Placebo Daily x24wks | 15 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | ACE Inhibitor | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 15 Participants | 31 Participants |
| Age, Continuous | 53 years | 54 years | 54 years |
| CD4+ T cell count | 349 cells/mm^3 | 392 cells/mm^3 | 362 cells/mm^3 |
| Race/Ethnicity, Customized Asian | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized Black/African American | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Hispanic/Latino | 0 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Pacific Islander | 0 participants | 1 participants | 1 participants |
| Race/Ethnicity, Customized White | 14 participants | 9 participants | 23 participants |
| Region of Enrollment United States | 16 participants | 15 participants | 31 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 16 Participants | 15 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 16 | 0 / 15 |
| serious Total, serious adverse events | 0 / 16 | 0 / 15 |
Outcome results
Primary
Change in HIV RNA (Copies/Million Rectal Cells)
Change in HIV RNA measured in GALT (gut-associated lymphoid tissue) from baseline
Time frame: 22 weeks
Population: Three participants in the placebo group did not have sufficient cells for analysis for one of the time points.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ACE Inhibitor | Change in HIV RNA (Copies/Million Rectal Cells) | 1.1 copies/million rectal cells |
| Placebo | Change in HIV RNA (Copies/Million Rectal Cells) | -0.2 copies/million rectal cells |
p-value: 0.63Wilcoxon (Mann-Whitney)
Secondary
Change in HIV DNA (Copies/Million Rectal Cells)
Change in HIV DNA measured in GALT (gut-associated lymphoid tissue) from baseline
Time frame: 22 weeks
Population: Three participants in the placebo group did not have sufficient cells for analysis for one of the time points.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| ACE Inhibitor | Change in HIV DNA (Copies/Million Rectal Cells) | -38.4 copies/million rectal cells |
| Placebo | Change in HIV DNA (Copies/Million Rectal Cells) | -53.8 copies/million rectal cells |
p-value: 0.63Wilcoxon (Mann-Whitney)