Vachiat A, McCutcheon K, Tsabedze N, et al. HIV and ischemic heart disease. J Am Coll Cardiol. 2017;69:73-82.
Grunfeld C. Dyslipidemia and its treatment in HIV infection. Top HIV Med. 2010;18:112-118.
El-Sadr WM, Mullin CM, Carr A, et al. Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naive cohort. HIV Med. 2005;6:114-121.
Strategies for Management of Antiretroviral Therapy (SMART) Study Group. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283-2296.
Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;63:2889-2934.
Jacobson TA, Ito MK, Maki KC, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 - executive summary. J Clin Lipidol. 2014;8:473-488.
US Food and Drug Administration. Drug safety communication: interactions between certain HIV or hepatitis C drugs and cholesterol-lowering statin drugs can increase the risk of muscle injury. https://www.fda.gov/Drugs/DrugSafety/ucm293877.htm. Accessed August 2018.
Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380:565-571.
Aberg JA, Sponseller CA, Ward DJ, et al. Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia (INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomised, double-blind, superiority trial. Lancet HIV. 2017;4:e284-e294.
Toribio M, Fitch KV, Sanchez L, et al. Effects of pitavastatin and pravastatin on markers of immune activation and arterial inflammation in HIV. AIDS. 2017;31:797-806.
ClinicalTrials.gov. Evaluating the use of pitavastatin to reduce the risk of cardiovascular disease in HIV-infected adults (REPRIEVE). https://clinicaltrials.gov/ct2/show/NCT02344290. Accessed August 2018.
Ladapo JA, Richards AK, DeWitt CM, et al. Disparities in the quality of cardiovascular care between HIV-infected versus HIV-uninfected adults in the United States: a cross-sectional study. J Am Heart Assoc. 2017;6:e007107.
Hsue P, Ribaudo H, Deeks SG, et al. Impact of LDMTX on immune activation and endothelial function in treated HIV. 25th Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2018. Boston. Abstract 79.
Tawakol A, Ribaudo H, Isha AE, et al. Impact of methotrexate on arterial inflammation in persons with treated HIV. Conference on Retroviruses and Opportunistic Infections (CROI). March 4-7, 2018. Boston. Abstract 684LB.
Hsue P, Deeks SG, Ishai AE, et al. IL-1β inhibition significantly reduces atherosclerotic inflammation in treated HIV in treated HIV. In: Program and abstracts of the Conference on Retroviruses and Opportunistic Infections, Seattle, Washington, 13-17 February 2016. Abstract 126.
Malvestutto CD, Aberg JA. Challenges of statins in HIV hyperlipidemia. US Endocrinology. 2013;9:157-165.
Jacobson TA, Maki KC, Orringer CE, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: Part 2. J Clin Lipidol. 2015;9:S1-122.e1.
Silverman MG, Ference BA, Im K, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016;316:1289-1297.

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Moderator

Steven Grinspoon, MD

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

Disclosures

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.

Panelist

Karen E. Aspry, MD

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

Disclosures

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.

Editors

Joy P. Marko, MS, APN-C, CCMEP

Scientific Director, Medscape, LLC

Disclosures

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

Kalanethee Paul-Pletzer, PhD

Scientific Director, Medscape, LLC

Disclosures

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

Disclosures

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

CME / ABIM MOC / CE

Statins and HIV: Tailoring Therapy to Optimize Outcomes

Authors: Steven Grinspoon MD; Karen E. Aspry, MD
CME / ABIM MOC / CE Released: 9/19/2018
THIS ACTIVITY HAS EXPIRED FOR CREDIT
Valid for credit through: 9/19/2019, 11:59 PM EST

Start Activity

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

Disclosures

Moderator

Steven Grinspoon, MD

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

Disclosures

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.

Panelist

Karen E. Aspry, MD

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

Disclosures

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.

Editors

Joy P. Marko, MS, APN-C, CCMEP

Scientific Director, Medscape, LLC

Disclosures

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

Kalanethee Paul-Pletzer, PhD

Scientific Director, Medscape, LLC

Disclosures

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

Disclosures

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

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From Medscape Education Cardiology

CME / ABIM MOC / CE

Statins and HIV: Tailoring Therapy to Optimize Outcomes

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

THIS ACTIVITY HAS EXPIRED FOR CREDIT

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

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

processing....

Statins and HIV: Tailoring Therapy to Optimize Outcomes
[ CLOSE WINDOW ]

Slide 1.

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
[ CLOSE WINDOW ]

Slide 2.

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
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Slide 3.

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
[ CLOSE WINDOW ]

Slide 4.

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)
[ CLOSE WINDOW ]

Slide 5.

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
[ CLOSE WINDOW ]

Slide 6.

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
[ CLOSE WINDOW ]

Slide 7.

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
[ CLOSE WINDOW ]

Slide 8.

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
[ CLOSE WINDOW ]

Slide 9.

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
[ CLOSE WINDOW ]

Slide 10.

JUPITER: CV Benefits and Diabetes Risk^[8]
- Statins are associated with new-onset diabetes
- Diabetes risk is outweighed by CV benefit of statins
[ CLOSE WINDOW ]

Slide 11.

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
[ CLOSE WINDOW ]

Slide 12.

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
[ CLOSE WINDOW ]

Slide 13.

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
[ CLOSE WINDOW ]

Slide 14.

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
[ CLOSE WINDOW ]

Slide 15.

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
[ CLOSE WINDOW ]

Slide 16.

Other Anti-Inflammatory Strategies for HIV-Infected Individuals^[13-15]
[ CLOSE WINDOW ]

Slide 17.

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
[ CLOSE WINDOW ]

Slide 18.

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
[ CLOSE WINDOW ]

Slide 19.

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
[ CLOSE WINDOW ]

Slide 20.

Summary
[ CLOSE WINDOW ]

Slide 21.

Thank you
[ CLOSE WINDOW ]

Slide 22.

This content has been condensed for improved clarity.

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The educational activity presented above may involve simulated case-based scenarios. The patients depicted in these scenarios are fictitious and no association with any actual patient is intended or should be inferred.

The material presented here does not necessarily reflect the views of Medscape, LLC, or companies that support educational programming on medscape.org. These materials may discuss therapeutic products that have not been approved by the US Food and Drug Administration and off-label uses of approved products. A qualified healthcare professional should be consulted before using any therapeutic product discussed. Readers should verify all information and data before treating patients or employing any therapies described in this educational activity.

References

Faculty and Disclosures

Moderator

Steven Grinspoon, MD

Panelist

Karen E. Aspry, MD

Editors

Joy P. Marko, MS, APN-C, CCMEP

Kalanethee Paul-Pletzer, PhD

CME / CE Reviewer

Amy Bernard, MS, BSN, RN-BC, CHCP

CME / ABIM MOC / CE

Statins and HIV: Tailoring Therapy to Optimize Outcomes

Target Audience and Goal Statement

Disclosures

Moderator

Steven Grinspoon, MD

Panelist

Karen E. Aspry, MD

Editors

Joy P. Marko, MS, APN-C, CCMEP

Kalanethee Paul-Pletzer, PhD

CME / CE Reviewer

Amy Bernard, MS, BSN, RN-BC, CHCP

Accreditation Statements

For Physicians

For Nurses

For Pharmacists

Instructions for Participation and Credit

Statins and HIV: Tailoring Therapy to Optimize Outcomes

Statins and HIV: Tailoring Therapy to Optimize Outcomes

Slide 1.

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

Slide 2.

Reasons for Increased ASCVD Risk in HIV Infection[1]

Slide 3.

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

Slide 4.

Decline in MI in ART-Treated Individuals[2]

Slide 5.

SMART: Episodic vs Continuous ART[4]

Slide 6.

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

Slide 7.

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

Slide 8.

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

Slide 9.

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

Slide 10.

JUPITER: CV Benefits and Diabetes Risk[8]

Slide 11.

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

Slide 12.

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

Slide 13.

REPRIEVE: CV Outcomes Trial[11]

Slide 14.

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

Slide 15.

Challenges Associated With Statin Therapy in HIV-Infected Population

Slide 16.

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

Slide 17.

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

Slide 18.

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

Slide 19.

Team-Based Care

Slide 20.

Summary

Slide 21.

Thank you

Slide 22.

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

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

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

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

SMART: Episodic vs Continuous ART^[4]

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

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

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

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

JUPITER: CV Benefits and Diabetes Risk^[8]

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

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

REPRIEVE: CV Outcomes Trial^[11]

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

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

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

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