Acquired Immune Deficiency Syndrome Virus
Conditions
Keywords
immune activation, antiretroviral therapy, atorvastatin, immune exhaustion, adults, Africa
Brief summary
We hypothesise that atorvastatin changes immune activation among HAART-treated adults with suboptimal cluster cell differentiation 4 (CD4) recovery by 25%
Detailed description
The investigators have previously shown that up to 40% of HAART-treated adults have suboptimal CD4 recovery despite viral suppression. The investigators have also shown that immune activation and exhaustion are significantly higher among patients that do not exhibit satisfactory rise in CD4 counts despite viral suppression (suboptimal responders); when compared with their counterparts with viral suppression and satifactory CD4 count recovery (optimal responders). Given that atorvastatin changes immune activation in this pilot study, then larger studies can be done to understand its effect on CD4 count increase among suboptimal responders.
Interventions
DRUGPlacebo
PBMC collected for immune activation assays using flowcytometry
OTHERatorvastatin, Lipitor®
PBMC collected for immune activation assays using flowcytometry
Sponsors
Vaccine and Gene Therapy Institute, Florida
Makerere University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
List of inclusion Criteria: HIV-infected adults on antiretroviral therapy for at least 6 years with sustained viral suppression (viral load\<400 copies), and CD4 increase below 300 cells (difference between current and baseline CD4 count). List of
Exclusion criteria
History of an opportunistic infection within the previous six months, Pregnancy, History of myositis, History of ingestion of lipid-lowering agents at the baseline visit, Use of therapeutic agents known to have substantial drug-drug interactions with statins, and individuals on PI-containing HAART
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Immune Activation Levels After 12 Weeks of Atorvastatin 80mg Daily | 12 weeks | Immune activation was measured by co-expression of CD38 and HLADR on CD4 T-cells (CD4+CD38+HLADR+) Mean percentage change at 12 weeks was calculated |
Participant flow
Recruitment details
30 participants were recruited from the Infectious Diseases Institute research cohort (single site) and followed up for 12 weeks, 4 weeks wash out period and 12 weeks after cross over of treatment assignment
Pre-assignment details
Participants were selected if they had sustained viral suppression for 7 years and CD4 increases below 300 cells/ul
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin First, Then Placebo Intervention is atorvastatin, Lipitor® (40mg) 2 tablets daily (as adjuvant to HAART) for 12 weeks.
PBMC will be collected for immune activation assays using flowcytometry
'atorvastatin, Lipitor®': PBMC were collected for immune activation assays using flowcytometry | 15 |
| Placebo First, Then Atorvastatin Intervention for the placebo comparator arm is Placebo 2 tablets daily for 12 weeks PBMC will be collected for immune activation assays using flowcytometry
Placebo: PBMC were collected for immune activation assays using flowcytometry | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Atorvastatin First, Then Placebo | Placebo First, Then Atorvastatin | 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 | 15 Participants | 15 Participants | 30 Participants |
| Age, Continuous | 41 years | 47 years | 46 years |
| CD4 T-cell activation | 4.2 percenatage of activated CD4 T-cells | 2.9 percenatage of activated CD4 T-cells | 4.2 percenatage of activated CD4 T-cells |
| Region of Enrollment Uganda | 15 participants | 15 participants | 30 participants |
| Sex: Female, Male Female | 7 Participants | 10 Participants | 17 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 15 | 9 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Percentage Change in Immune Activation Levels After 12 Weeks of Atorvastatin 80mg Daily
Immune activation was measured by co-expression of CD38 and HLADR on CD4 T-cells (CD4+CD38+HLADR+) Mean percentage change at 12 weeks was calculated
Time frame: 12 weeks
Population: There was no cross-over or carry-over effect (the sequence did not matter), so we present data for 30 patients for their 12 weeks exposure to atorvastatin
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atorvastatin | Percentage Change in Immune Activation Levels After 12 Weeks of Atorvastatin 80mg Daily | 60 percentage change in activated T-cells |
| Placebo | Percentage Change in Immune Activation Levels After 12 Weeks of Atorvastatin 80mg Daily | 21 percentage change in activated T-cells |
p-value: <0.05Wilcoxon (Mann-Whitney)