HIV, Hypercholesterolaemia
Conditions
Keywords
Hypercholesterolaemia, HIV, Rosuvastatin, Protease inhibitor switching
Brief summary
To compare the effect of rosuvastatin to protease inhibitor switching on fasting total cholesterol over 12 weeks.
Detailed description
To compare the effects of rosuvastatin to protease inhibitor switching on: * Total cholesterol through week 12 * Safety parameters (HIV viral load, clinical adverse events, serious adverse events, laboratory adverse events, modifications to antiretroviral therapy) * Quality of life (SF-12) * Fasting LDL cholesterol (estimated with Friedewald equation unless triglycerides \>400mg/dL, in which case LDL-C would be measured directly), HDL cholesterol, total : HDL cholesterol ratio, LDL particles sizes, triglycerides * Fasting glucose and insulin * Framingham cardiovascular risk score * D:A:D 5-year estimated risk calculator
Interventions
DRUGSwitch ritonavir-boosted PI
Switch their existing ritonavir-boosted PI to another potent ART drug with lesser effects on serum cholesterol selected by the investigator.
DRUGContinue Ritonavir-boosted PI+Rosuvastatin
Continue ritonavir-boosted PI-based ART and commence rosuvastatin 10 mg daily (5 mg daily in Asian participants).
Sponsors
Juan A. Arnaiz
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HIV-positive status * Adults (≥18 years of age) * Stable and well-tolerated combination ART including a ritonavir-boosted protease inhibitor for the previous 6 months * HIV RNA \<50 copies/mL for at least the preceding 3 months * Fasting total cholesterol ≥5.5 mmol/L (\>213 mg/dL) * Framingham risk score ≥8% at 10 years OR diabetes mellitus OR a family history of premature coronary artery disease in a first-degree relative * Provision of written, informed consent
Exclusion criteria
* Any statin in the previous 12 weeks * Previous statin-induced myopathy or hepatitis * History of coronary artery disease, stroke or any other indication for the use of statin therapy (hyperlipidaemia: genetic, secondary or idiopathic) * Concurrent use of: 1. oral corticosteroids use other than for replacement therapy (i.e. prednisolone 5-7.5 mg, hydrocortisone 20-30 mg, cortisone acetate 25-37.5 mg daily) 2. other immunosuppressive or immunomodulating drugs * Contraindication to rosuvastatin therapy: 1. liver transaminases \>5 times the upper normal limit 2. creatinine clearance \<30 mL/min 3. known myopathy 4. current fibrate therapy 5. known resistance to one or more backbone ART drugs * No potent switch ART drug available to replace the current ritonavir-boosted protease inhibitor * Known intolerance to rosuvastatin or the proposed switch ART drug * Women attempting or likely to become pregnant, or who are pregnant or breast-feeding * A patient with a history or current evidence of any condition, therapy, or laboratory abnormality, or other circumstance that might confound the results of the study, or interfere with the patient's participation for the full duration of the study * Unable to complete study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change From Baseline in Total Cholesterol at 12 Weeks. | 12 weeks from baseline (week 0 to week 12) | The outcome was defined as the percentage change in fasting total cholesterol from baseline (week 0) to week 12. Fasting blood samples were collected after a 12-hour fast, and total cholesterol was measured in mmol/L. The percentage change was calculated for each participant and compared between the rosuvastatin and PI/r switch groups using an intention-to-treat analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Parameters (HIV Viral Load, Clinical Adverse Events, Serious Adverse Events, Laboratory Adverse Events, Modifications to Antiretroviral Therapy) | 12 weeks | — |
| Quality of Life (SF-12) | 12 weeks | — |
| Fasting LDL Cholesterol (Estimated With Friedewald Equation Unless Triglycerides >400mg/dL, in Which Case LDL-C Would be Measured Directly), HDL Cholesterol, Total : HDL Cholesterol Ratio, LDL Particles Sizes, Triglycerides | 12 weeks | — |
| Total Cholesterol Through Week 12 | 12 weeks | — |
| Framingham Cardiovascular Risk Score (10-year Risk Estimate) | Screening and week 12 | The Framingham Risk Score is a sex-specific algorithm used to estimate the 10-year risk of developing cardiovascular disease (CVD), including coronary heart disease, stroke, peripheral artery disease, and heart failure. It is based on factors such as age, sex, total cholesterol, HDL cholesterol, systolic blood pressure, treatment for hypertension, smoking status, and diabetes. Scale Title: Framingham 10-Year Cardiovascular Risk Score Minimum Value: 0% Maximum Value: 100% Interpretation: Higher scores indicate a worse outcome, meaning a higher estimated risk of developing cardiovascular disease within 10 years. |
| D:A:D 5-year Estimated Risk Calculator. | Screening and week 12. | — |
| Fasting Glucose and Insulin. | 12 weeks | — |
Countries
Spain
Participant flow
Recruitment details
Participants were recruited between June 2012 and April 2014 across nine clinical sites in Australia and Spain, including hospitals and private HIV clinics. Recruitment targeted HIV-1-infected adults with controlled viral load and elevated cardiovascular risk, not currently on lipid-lowering therapy.
Pre-assignment details
After providing informed consent, participants underwent a screening period of up to 14 days to confirm eligibility. This included fasting blood tests, cardiovascular risk assessment (Framingham score), and confirmation of stable ART. Participants were excluded prior to randomization if they did not meet inclusion criteria (e.g., cholesterol \<5.5 mmol/L, low cardiovascular risk, or contraindications to study drugs). No washout or run-in period was required.
Participants by arm
| Arm | Count |
|---|---|
| PI/r Switch Group Switch their existing ritonavir-boosted PI to another potent ART drug with lesser effects on serum cholesterol selected by the investigator.
Switch ritonavir-boosted PI: Switch their existing ritonavir-boosted PI to another potent ART drug with lesser effects on serum cholesterol selected by the investigator. | 20 |
| Rosuvastatin Continue ritonavir-boosted PI-based ART and commence rosuvastatin 10 mg daily (5 mg daily in Asian participants).
Continue Ritonavir-boosted PI+Rosuvastatin: Continue ritonavir-boosted PI-based ART and commence rosuvastatin 10 mg daily (5 mg daily in Asian participants). | 23 |
| Total | 43 |
Baseline characteristics
| Characteristic | PI/r Switch Group | Total | Rosuvastatin |
|---|---|---|---|
| Age, Continuous | 56 years STANDARD_DEVIATION 8.2 | 55 years STANDARD_DEVIATION 8.5 | 53 years STANDARD_DEVIATION 8.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 19 Participants | 41 Participants | 22 Participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 20 Participants | 42 Participants | 22 Participants |
| Total cholesterol | 6.0 mmol/L STANDARD_DEVIATION 0.9 | 6.2 mmol/L STANDARD_DEVIATION 1.2 | 6.3 mmol/L STANDARD_DEVIATION 1.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 20 | 0 / 23 |
| other Total, other adverse events | 14 / 20 | 14 / 23 |
| serious Total, serious adverse events | 1 / 20 | 1 / 23 |
Outcome results
Primary
Percentage Change From Baseline in Total Cholesterol at 12 Weeks.
The outcome was defined as the percentage change in fasting total cholesterol from baseline (week 0) to week 12. Fasting blood samples were collected after a 12-hour fast, and total cholesterol was measured in mmol/L. The percentage change was calculated for each participant and compared between the rosuvastatin and PI/r switch groups using an intention-to-treat analysis.
Time frame: 12 weeks from baseline (week 0 to week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PI/r Switch Group | Percentage Change From Baseline in Total Cholesterol at 12 Weeks. | 8.7 Percentage Change (%) | Standard Deviation 10.8 |
| Rosuvastatin | Percentage Change From Baseline in Total Cholesterol at 12 Weeks. | 21.4 Percentage Change (%) | Standard Deviation 19.2 |
Comparison: Comparison of percentage change in fasting total cholesterol from baseline to week 12 between rosuvastatin and PI/r switch groups. Wilcoxon rank-sum test used. Study powered to detect a 15% difference with 80% power and α = 0.05. All participants included in intention-to-treat analysis.p-value: 0.00395% CI: [2.9, 22.5]Wilcoxon (Mann-Whitney)
Secondary
D:A:D 5-year Estimated Risk Calculator.
Time frame: Screening and week 12.
Secondary
Fasting Glucose and Insulin.
Time frame: 12 weeks
Secondary
Fasting LDL Cholesterol (Estimated With Friedewald Equation Unless Triglycerides >400mg/dL, in Which Case LDL-C Would be Measured Directly), HDL Cholesterol, Total : HDL Cholesterol Ratio, LDL Particles Sizes, Triglycerides
Time frame: 12 weeks
Secondary
Framingham Cardiovascular Risk Score (10-year Risk Estimate)
The Framingham Risk Score is a sex-specific algorithm used to estimate the 10-year risk of developing cardiovascular disease (CVD), including coronary heart disease, stroke, peripheral artery disease, and heart failure. It is based on factors such as age, sex, total cholesterol, HDL cholesterol, systolic blood pressure, treatment for hypertension, smoking status, and diabetes. Scale Title: Framingham 10-Year Cardiovascular Risk Score Minimum Value: 0% Maximum Value: 100% Interpretation: Higher scores indicate a worse outcome, meaning a higher estimated risk of developing cardiovascular disease within 10 years.
Time frame: Screening and week 12
Secondary
Quality of Life (SF-12)
Time frame: 12 weeks
Secondary
Safety Parameters (HIV Viral Load, Clinical Adverse Events, Serious Adverse Events, Laboratory Adverse Events, Modifications to Antiretroviral Therapy)
Time frame: 12 weeks
Secondary
Total Cholesterol Through Week 12
Time frame: 12 weeks