Cardiovascular Prevention for Persons With HIV

Study Overview
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Brief Summary
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This study is funded by the American Heart Association. The goal of this research is to prevent early cardiovascular damage before symptoms develop for persons with HIV infection. Evidence suggests that taking low doses of blood pressure and cholesterol medication reduces risk for heart disease in persons who are at increased risk (such as the case with HIV infection). Participants who are taking HIV treatment with an 'undetectable' viral load, and who do NOT need treatment for high blood pressure or cholesterol may be eligible to enroll. Participants will take a low dose cholesterol medication (or placebo) and a low dose of a blood pressure medication (or a placebo), and will be seen at 3 study visits over 4 months.

Official Title
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Cardiovascular Disease Risk Reduction for Persons With HIV Infection: a Polypill Pilot Study

Conditions
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HIV Infection, Cardiovascular Disease Risk

Intervention / Treatment
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* Drug: Pravastatin
* Drug: Lisinopril


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV Infection with viral load 'undetectable' while taking antiretroviral therapy Age ≥40 Framingham risk score (FRS) ≥5%, or ≥3% with ≥5 years of exposure to antiretroviral therapy Exclusion Criteria: Known cardiovascular disease or Framingham risk score (FRS) ≥20% Blood pressure ≥140/90 LDL cholesterol ≥160 (with FRS <10%), or ≥130 (with FRS 10-20%) Currently taking, or has a medication contraindication to take, a 'statin', an ACE inhibitor, or an angiotensin receptor blocker medication Cirrhosis or plasma ALT/AST levels >2x upper limit of normal Chronic kidney disease and a creatinine >2.0mg/dL Triglycerides >500mg/dL

Ages Eligible for Study
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Minimum Age: 40 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: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lisinopril<br>Lisinopril 10mg once daily | Drug: Lisinopril<br>* Participants randomized to take lisinopril (active) or matching placebo pill once daily<br>|
| Placebo Comparator: Lisinopril Placebo<br>Placebo pill (matched to lisinopril) once daily | Drug: Lisinopril<br>* Participants randomized to take lisinopril (active) or matching placebo pill once daily<br>|
| Experimental: Pravastatin<br>Pravastatin 20mg once daily | Drug: Pravastatin<br>* Participants randomized to take pravastatin (active) or matching placebo pill once daily<br>|
| Placebo Comparator: Pravastatin placebo<br>Placebo pill (matched to pravastatin) once daily | Drug: Pravastatin<br>* Participants randomized to take pravastatin (active) or matching placebo pill once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who Stated (by Self-report) That They Had Side Effects | Participants were asked at each visit if they had any side effects to study medication. They provided a yes or no answer, and if yes they specified what the side effect was. | 4 months | 
| Number of Participants Who Took >90% of Their Doses (by Pill Count) | The number of pills missing from study medication bottles was counted by study nurses at the completion of the study. The proportion of pills taken divided by the number of days the participant was enrolled in the study was calculated, and multiplied by 100, to generate the '% of doses taken' | 4 months | 
| Change From Baseline to Month 4 in the Framingham Risk Score (FRS) | The Framingham Risk Score is calculated by a published algorithm that predicts a patients risk of having a coronary heart disease event in the next 10 years. The measures that are considering in predicting this risk are: age, blood pressure, cholesterol (both total cholesterol and high-density lipoprotein cholesterol), smoking status, and use of medication to treat hypertension. This risk score can be estimated using an online calculator (http://hp2010.nhlbihin.net/atpiii/calculator.asp) | Change from baseline to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Blood Pressure | Blood pressure was assessed by standard clinical methods (i.e., the same way it is measured during a routine clinic visit) | change from baseline to 4 months | 
| Changes in Blood Lipids | Blood lipids include routine cholesterol measurements that are monitored in clinical practice. They are measured in blood after a blood draw is performed. The specific measurements include: a) total cholesterol, b) low-density lipoprotein cholesterol, c) high-density lipoprotein cholesterol, and d) triglycerides | change from baseline to 4 months | 
| Changes in Small Artery Elasticity | Small artery elasticity is a measure of vascular function, estimated through analysis of the blood pressure waveform. A sensor is placed on wrist over the radial pulse. The blood pressure waveform of the pulse is recorded and analyzed the elasticity, or compliance, of the small (and large) vasculature. Impaired artery elasticity, or increased stiffness, is an early sign of vascular disease that predicts risk for future cardiovascular events. | change from baseline to 4 months | 
| Changes hsCRP (C-reactive Protein) | This biomarker represents systemic inflammation within in the body. | change from baseline to 4 months | 
| Changes IL-6 (Interleukin-6) | This biomarker represents systemic inflammation within in the body. | change from baseline to 4 months | 
| Changes TNFa (Tumor Necrosis Factor Alpha) | This biomarker represents systemic inflammation within in the body. | change from baseline to 4 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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treatment experienced