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Statins and HIV: Tailoring Therapy to Optimize Outcomes

  • Authors: Steven Grinspoon MD; Karen E. Aspry, MD
  • CME / ABIM MOC / CE Released: 9/19/2018
  • Valid for credit through: 9/19/2019, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for cardiologists, infectious disease/HIV specialists, diabetologists, endocrinologists, nurses, nurse practitioners, and pharmacists.

The goal of this activity is to improve cardiovascular outcomes in HIV-infected individuals with the use of appropriate statin therapy.

Upon completion of this activity, participants will be able to:

  • Have increased knowledge regarding
    • Common challenges associated with treatment of dyslipidemia in patients who are HIV positive
    • Differences between currently available statins in terms of drug-drug interactions with antiretroviral therapy (ART)
    • Coordinated team-based care to promote treatment adherence in patients with dyslipidemia who are HIV positive
  • Have greater competence related to
    • Tailoring lipid-lowering therapy in patients who are HIV positive to optimize cardiovascular disease (CVD) risk reduction


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  • Steven Grinspoon, MD

    Professor of Medicine
    Harvard Medical School
    MGH Endowed Chair in Neuroendocrinology and Metabolism
    MGH Program in Nutritional Metabolism and Nutrition Obesity Research Center at Harvard
    Boston, Massachusetts


    Disclosure: Steven Grinspoon, MD, has disclosed the following relevant financial relationships:
    Received grants for clinical research from: Gilead Sciences, Inc.; Kowa Company Ltd.; Theratechnologies Inc.

    Dr Grinspoon does not intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the FDA for use in the United States.

    Dr Grinspoon does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States.


  • Karen E. Aspry, MD

    Assistant Professor of Medicine (Clinical)
    Alpert Medical School
    Brown University
    Lipid and Prevention Program
    Lifespan CV Institute
    Providence, Rhode Island


    Disclosure: Karen E. Aspry, MD, has disclosed the following relevant financial relationships:
    Other: Contracted research: Akcea Therapeutics; Amgen Inc.; Ionis Pharmaceuticals, Inc.

    Dr Aspry does intend to discuss off-label uses of drugs, mechanical devices, biologics, or diagnostics approved by the FDA for use in the United States.

    Dr Aspry does not intend to discuss investigational drugs, mechanical devices, biologics, or diagnostics not approved by the FDA for use in the United States.


  • Joy P. Marko, MS, APN-C, CCMEP

    Scientific Director, Medscape, LLC


    Disclosure: Joy P. Marko, MS, APN-C, CCMEP, has disclosed no relevant financial relationships.

  • Kalanethee Paul-Pletzer, PhD

    Scientific Director, Medscape, LLC


    Disclosure: Kalanethee Paul-Pletzer, PhD, has disclosed no relevant financial relationships.

CME / CE Reviewer

  • Amy Bernard, MS, BSN, RN-BC, CHCP

    Lead Nurse Planner, Medscape, LLC


    Disclosure: Amy Bernard, MS, BSN, RN-BC, CHCP, has disclosed no relevant financial relationships.

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Statins and HIV: Tailoring Therapy to Optimize Outcomes

Authors: Steven Grinspoon MD; Karen E. Aspry, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 9/19/2018

Valid for credit through: 9/19/2019, 11:59 PM EST


  • Statins and HIV: Tailoring Therapy to Optimize Outcomes

  • Slide 1.

    Slide 1.

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  • Understanding the Changing CV Risk Burden in HIV Infection[1]

    • Cardiovascular (CV) risk is significantly elevated in HIV-infected individuals
    • There is a high prevalence of myocardial infarctions (MIs), ischemic stroke, and peripheral arterial disease
    • Multiple risk factors contribute to the increased risk

  • Slide 2.

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  • Reasons for Increased ASCVD Risk in HIV Infection[1]

    • Higher prevalence of traditional risk factors in HIV-infected vs general population including
      • Smoking (3-fold higher)
      • Insulin resistance
      • Nephrotic syndrome
    • Traditional risk factors account for approximately 25% of the excess risk
    • Remaining 75% of excess risk is due to nontraditional risk factors:
      • Inflammation
      • Immune activation
      • Dysregulated lipid and glucose metabolism
    • HIV infection is a disease of immune dysfunction, but there is simultaneous immune activation
    • HIV targets proteins involved in lipid and glucose metabolism, accelerating atherosclerosis
      • Example: It interferes with lipoprotein lipase and cholesterol efflux from macrophages

  • Slide 3.

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  • Lipid Changes in HIV-Infected Individuals[2,3]

    • Dyslipidemia in HIV individuals is likely due to insulin resistance
    • Older antiretroviral therapy (ART) agents doubled the risk of MI in HIV-infected individuals
    • Newer ART agents (newer protease inhibitors [PIs] and integrase inhibitors) are not associated with increased MI risk
    • Early, continuous ART improves HIV outcomes without increasing CV events

  • Slide 4.

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  • Decline in MI in ART-Treated Individuals[2]

    • Relative rate of MI had reduced to about 1.3-fold in the period 2006-2008 from >2-fold in prior years
    • Declining rate of MI was paralleled by increasing use of lipid-lowering therapy (LLT)

  • Slide 5.

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  • SMART: Episodic vs Continuous ART[4]

    • Continuous ART significantly reduced CV events
    • Viral suppression, however, does not completely suppress inflammation
    • ART alone is not sufficient to reduce elevated CV risk in the HIV population

  • Slide 6.

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  • Assessment of CV Risk for Primary Prevention in HIV-Infected Individuals[5]

    • Perform lipid and glucose panel test before starting ART or before a change in ART
    • Repeat the tests every 6 months thereafter
    • Adopt a holistic approach to risk assessment by assessing all traditional risk factors
    • Use of the 2013 ACC/AHA ASCVD risk calculator in the HIV population is unclear

  • Slide 7.

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  • Match Lipid Treatment to Level of Risk: Per NLA, Count Risk Factors, Add HIV as Additional Factor[6]

    • The National Lipid Association (NLA) recommends counting HIV as an additional risk factor
    • Treatment goals are based on risk category
    • HIV patients may not necessarily have elevated low-density lipoprotein cholesterol (LDL-C), but they have an atherogenic lipid profile:
      • Elevated non-high-density lipoprotein cholesterol (HDL-C)
      • Oxidized LDL
      • Small LDL particles

  • Slide 8.

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  • ACC/AHA: Lifestyle as the Foundation for ASCVD Risk-Reduction Efforts[5]

    • Engage in shared decision making with the patient
    • Ensure patient understands the need for therapy
    • Recognize that statins are the drugs of choice for atherosclerotic cardiovascular disease (ASCVD) risk reduction, unless triglycerides are >500 mg/dL
    • Statins are relatively safe for use in the HIV population with no increased risk of myopathy or liver dysfunction
    • Statins have other pleiotropic properties; they lower C-reactive protein and other immune activation indices, and coronary plaque
    • Coronary plaque in HIV is a noncalcified plaque as opposed to calcified plaques in traditional models of ASCVD

  • Slide 9.

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  • Drug-Drug Interactions: Use of Statins With PIs[7]

    • Not all statins are equal
    • Some statins are inappropriate in patients with HIV due to drug-drug interactions with ART
    • Pitavastatin is not metabolized via the cytochrome P450 3A4 (CYP3A) system and has no significant interaction with other ART
    • Review statin label and select doses that are appropriate for the ART the patient is taking

  • Slide 10.

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  • JUPITER: CV Benefits and Diabetes Risk[8]

    • Statins are associated with new-onset diabetes
    • Diabetes risk is outweighed by CV benefit of statins

  • Slide 11.

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  • INTREPID: Pitavastatin vs Pravastatin in ART-Treated HIV-1-Infected Individuals With Dyslipidemia[9]

    • Pitavastatin and pravastatin do not depend on cytochrome P450 for primary metabolism
    • Both were effective in reducing LDL-C -- pitavastatin to a greater extent than pravastatin

  • Slide 12.

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  • INTREPID: Markers of Immune Activation and Arterial Inflammation[10]

    • Pitavastatin and pravastatin reduced key markers of inflammation -- pitavastatin to a greater extent
    • Both statins did not increase glucose levels

  • Slide 13.

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  • REPRIEVE: CV Outcomes Trial[11]

    • A large, randomized, placebo-controlled trial of pitavastatin for the primary prevention of CV events
    • First outcome trial in the HIV population with major adverse cardiovascular event (MACE) as an endpoint
    • Previous trials used surrogate endpoints such as lipid lowering

  • Slide 14.

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  • Disparities in CV Care in the United States: HIV-Infected vs HIV-Uninfected Adults With CV Risk Factors[12]

    • Adherence to statin therapy is low in both the HIV-infected and noninfected population

  • Slide 15.

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  • Challenges Associated With Statin Therapy in HIV-Infected Population

    • Pill burden is a major contributing factor of nonadherence to statin therapy
      • ART agents are being grouped together into a single pill to reduce pill burden
      • The polypill for the HIV-infected population could be ART plus an anti-inflammatory/antilipid strategy
    • Early initiation of statin treatment is another challenge
      • At present, ART is being initiated as soon as a diagnosis of HIV is made
      • Statin treatment should also be considered as early as possible

  • Slide 16.

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  • Other Anti-Inflammatory Strategies for HIV-Infected Individuals[13-15]

  • Slide 17.

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  • Statin Therapy Considerations in HIV-Infected Individuals[6,16,17]

    • LDL-C reduction is the main driver of CV risk reduction
    • Important to treat to reduce LDL-C by ≥50%
    • Ezetimibe is safe in patients with HIV and can be added to statins to reach target LDL-C reduction
    • Reduce saturated fat content in the diet

  • Slide 18.

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  • Association Between Lowering LDL-C and CV Risk Reduction: Systematic Review and Meta-Analysis[18]

    • Anti-inflammatory pleiotropic effects of statins may further lower CV risk
    • Need to maximize therapy to lower both traditional and nontraditional risk factors
    • Lifestyle management is an equally important component of risk reduction
    • Smoking cessation efforts should be a priority in HIV patients
    • Risk of CV events in HIV-positive patients decrease with increasing time since smoking cessation

  • Slide 19.

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  • Team-Based Care

    • Patients with HIV are treated by a variety of healthcare providers (HCPs)
    • Coordination and collaboration between the different HCPs is critical for effective management of dyslipidemia
    • Educate the patient on the rationale for statin therapy
    • Use behavioral approaches to improve adherence to statin therapy and diet/lifestyle
    • Follow up patients frequently

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  • This content has been condensed for improved clarity.

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