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

Study Overview
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Brief Summary
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To compare the effect of rosuvastatin to protease inhibitor switching on fasting total cholesterol over 12 weeks.

Detailed Description
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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

Official Title
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Rosuvastatin Versus Protease Inhibitor Switching for Hypercholesterolaemia in HIV-infected Adults

Conditions
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HIV, Hypercholesterolaemia

Intervention / Treatment
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* Drug: Switch ritonavir-boosted PI
* Drug: Continue Ritonavir-boosted PI+Rosuvastatin


Participation Criteria
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Eligibility Criteria
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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: 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) other immunosuppressive or immunomodulating drugs Contraindication to rosuvastatin therapy: liver transaminases >5 times the upper normal limit creatinine clearance <30 mL/min known myopathy current fibrate therapy 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Switch ritonavir-boosted PI<br>Switch their existing ritonavir-boosted PI to another potent ART drug with lesser effects on serum cholesterol selected by the investigator. | Drug: Switch ritonavir-boosted PI<br>* Switch their existing ritonavir-boosted PI to another potent ART drug with lesser effects on serum cholesterol selected by the investigator.<br>|
| Experimental: Continue ritonavir-boosted PI+Rosuvastatin<br>Continue ritonavir-boosted PI-based ART and commence rosuvastatin 10 mg daily (5 mg daily in Asian participants). | Drug: Continue Ritonavir-boosted PI+Rosuvastatin<br>* Continue ritonavir-boosted PI-based ART and commence rosuvastatin 10 mg daily (5 mg daily in Asian participants).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change from baseline in total cholesterol at 12 weeks. |  | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | Screening and week 12. | 
| D:A:D 5-year estimated risk calculator. |  | Screening and week 12. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypercholesterolaemia, HIV, Rosuvastatin, Protease inhibitor switching