Cardiovascular Prevention for Persons With HIV

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection; Cardiovascular Disease Risk
• Intervention / Treatment: Drug: Lisinopril; Drug: Pravastatin

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Hennepin Healthcare Research Institute
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Jason Baker, MD, Hennepin Faculty Associates

Publications and helpful links

General Publications

• Baker JV, Huppler Hullsiek K, Prosser R, Duprez D, Grimm R, Tracy RP, Rhame F, Henry K, Neaton JD. Angiotensin converting enzyme inhibitor and HMG-CoA reductase inhibitor as adjunct treatment for persons with HIV infection: a feasibility randomized trial. PLoS One. 2012;7(10):e46894. doi: 10.1371/journal.pone.0046894. Epub 2012 Oct 17.

Study record dates

Study Major Dates

• Study Start: September 1, 2009
• Primary Completion (Actual): December 1, 2010
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: September 22, 2009
• First Submitted That Met QC Criteria: September 22, 2009
• First Posted (Estimate): September 23, 2009

Study Record Updates

• Last Update Posted (Actual): November 22, 2017
• Last Update Submitted That Met QC Criteria: October 19, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: treatment experienced
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases; HIV Infections; Cardiovascular Diseases; Infections; Acquired Immunodeficiency Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Enzyme Inhibitors; Antimetabolites; Protease Inhibitors; Protective Agents; Cardiotonic Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Angiotensin-Converting Enzyme Inhibitors; Pravastatin; Lisinopril
• Other Study ID Numbers: PCC-003