Treatment With Rosuvastatin Versus Switching PI (Protease Inhibitor) in Patients HIV With High Cholesterol Levels

Phase 4

Completed

Interventions: Drug: Switch ritonavir-boosted PI
Drug: Continue Ritonavir-boosted PI+Rosuvastatin

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

Recruitment & Eligibility

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

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Switch ritonavir-boosted PI	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.
Continue ritonavir-boosted PI+Rosuvastatin	Continue Ritonavir-boosted PI+Rosuvastatin	Continue ritonavir-boosted PI-based ART and commence rosuvastatin 10 mg daily (5 mg daily in Asian participants).

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Total Cholesterol Through Week 12	12 weeks
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
Fasting Glucose and Insulin.	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.