HIV Infections
Conditions
Keywords
HIV, chloroquine, disease progression, inflammation, treatment naive
Brief summary
Summary: Chloroquine is a medication that in laboratory settings has significant anti-HIV effects in HIV infected T-cells. Chloroquine has been used safely for over 60 years for malaria treatment and prevention, and it also has significant anti-inflammatory effects. No formal study of chloroquine has been performed in people with HIV infection. Chloroquine is used worldwide and is quite inexpensive outside of the United States. If shown to be effective, chloroquine could be a very important tool worldwide in delaying HIV disease progression which would extend the time period without needing anti-retroviral therapy. In countries where anti-retroviral therapy is not available, this could be very helpful. This is an 8 week trial study requiring 3 study visits. Participants will be ask to take a once a day study medication (chloroquine or placebo) for 8 weeks and have three blood draws for CD4 counts, HIV viral loads, and other research tests. The visits are at study enrollment, 4 weeks, and 8 weeks.
Detailed description
Summary: A phase I randomized, double-blind, placebo controlled trial to investigate the efficacy of chloroquine to decrease T-cell activation and decrease viral load in early HIV. Scientific Rationale: Chloroquine has in vivo direct anti-HIV effects and an anti-inflammatory effect. These properties may be beneficial in reducing viral burden and immune activation therefore delaying HIV disease progression. Sample Size: 25 Length of Study: 8 weeks, \[enrollment + 2 follow up visits\]. Intervention: * Arm 1a: Chloroquine 250mg orally once daily for 8 weeks. * Arm 1b: Chloroquine 500mg orally once daily for 8 weeks. * Arm 2: Placebo once daily for 8 weeks. Measurements: * Blood draws at weeks: 0, 4, and 8 weeks. * CD4, viral load measurements will be communicated to the referring provider (with subject consent).
Interventions
250mg or 500mg PO (by mouth) QDay
DRUGPlacebo
Placebo once daily for 8 weeks
Sponsors
Minnesota Medical Foundation
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* HIV-1 infected adults * CD4 count \> 250 cells/mm3 * Not presently receiving HIV antiretroviral therapy (\> 6 months or naïve) * Viral load \> 3000 RNA copies/mL (3.5 log) * No planned HIV anti-retroviral therapy for 8 weeks
Exclusion criteria
* Prior retinal eye disease * CD4 \< 250 cells/µL * Renal failure * Active malignancy * Corticosteroid therapy * Age \< 18 or \> 65 years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HIV Viral Load Change | baseline and 8 weeks | HIV-1 viral load change between baseline and 8 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Immune Activation Assessed by Flow Cytometry Analysis From Baseline to 8 Weeks | 8 weeks | The Change in the percentages of CD38+ HLA-DR+ CD8 and CD4 memory T cells from baseline to 8 weeks. |
Countries
United States
Participant flow
Recruitment details
2006-2008 recruitment of volunteers in HIV care but electing to not receive ART.
Participants by arm
| Arm | Count |
|---|---|
| Chloroquine 500mg Chloroquine 500mg PO once daily x 8 weeks | 3 |
| Placebo Placebo once daily for 8 weeks | 4 |
| Chloroquine 250mg Chloroquine 250mg PO once daily x 8 weeks | 6 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo | Chloroquine 250mg | Chloroquine 500mg | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 6 Participants | 3 Participants | 13 Participants |
| Age, Continuous | 34 years STANDARD_DEVIATION 5 | 36 years STANDARD_DEVIATION 5 | 40 years STANDARD_DEVIATION 15 | 36.5 years STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 4 participants | 6 participants | 3 participants | 13 participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 3 | 0 / 4 | 0 / 6 |
| serious Total, serious adverse events | 1 / 3 | 1 / 4 | 0 / 6 |
Outcome results
Primary
HIV Viral Load Change
HIV-1 viral load change between baseline and 8 weeks
Time frame: baseline and 8 weeks
| Arm | Measure | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|
| Chloroquine 250mg or 500mg | HIV Viral Load Change | -.083 log10 copies/mL | Standard Deviation 0.5 |
| Placebo | HIV Viral Load Change | 0.0 log10 copies/mL | Standard Deviation 0.1 |
Secondary
Change in Immune Activation Assessed by Flow Cytometry Analysis From Baseline to 8 Weeks
The Change in the percentages of CD38+ HLA-DR+ CD8 and CD4 memory T cells from baseline to 8 weeks.
Time frame: 8 weeks
Population: Analysis of Chloroquine arms is pooled.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Chloroquine 250mg or 500mg | Change in Immune Activation Assessed by Flow Cytometry Analysis From Baseline to 8 Weeks | CD8 CD38+HLA-DR+ | -2.5 percentage change |
| Chloroquine 250mg or 500mg | Change in Immune Activation Assessed by Flow Cytometry Analysis From Baseline to 8 Weeks | CD4 ki67+ | -2.0 percentage change |
| Placebo | Change in Immune Activation Assessed by Flow Cytometry Analysis From Baseline to 8 Weeks | CD8 CD38+HLA-DR+ | 1.85 percentage change |
| Placebo | Change in Immune Activation Assessed by Flow Cytometry Analysis From Baseline to 8 Weeks | CD4 ki67+ | 1.4 percentage change |