Dyslipidemia and Cardiovascular Risk in Human Immunodeficiency Virus Infection

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Key points

  • Since the advent of effective antiretroviral therapy, cardiovascular disease has become a major cause of morbidity and mortality in the population with human immunodeficiency virus.

  • The pathogenesis of atherosclerosis in human immunodeficiency virus–infected individuals is complex, and proatherogenic quantitative and qualitative changes in lipids have a major role in this process.

  • HIV replication, chronic inflammation and immune activation, and exposure to antiretroviral drugs (either directly or

Factors other than dyslipidemia may contribute to accelerated atherosclerosis in HIV infection

Cardiovascular risk factors have a major role in development of CVD disease. HIV-infected subjects have higher prevalence of established CVD risk factors, such as smoking, hypertension, insulin resistance, and dyslipidemia, compared with age-matched individuals.9 Cocaine use, which is relatively common among some groups of HIV-infected patients, renal function, and albuminuria have also been associated with the risk for coronary artery disease in HIV-infected patients.9, 10 All of these risk

Host Factors in HIV-Infected Subjects May Contribute to Dyslipidemia Development

HIV-infected subjects have increased prevalence of dyslipidemia; however, it is unclear to what extent this is associated with specific host factors. In the D:A:D study, 33.8% and 22.2% of a group of treated HIV-infected individuals had elevated levels of triglyceride and TC, respectively.20 Longitudinal and cross-sectional studies have assessed the role of single-nucleotide polymorphisms on the incidence of dyslipidemia in HIV patients.21 The Multicenter AIDS Cohort Study showed that

Lipid changes during treated HIV disease may contribute to immune activation in HIV infection

A hallmark of HIV infection is activation of the immune system, which persists to some degree even after the initiation of effective ART.19 Although the exact mechanisms that drive this immune activation are unclear, residual HIV replication, microbial translocation, and inflammatory lipids are potential contributors. Modified lipoproteins such as oxidized LDL carry oxidized lipids and may regulate immunity.86 We recently showed that HIV-infected subjects have dysfunctional HDL that is

Diagnosis of Lipid Disorders in the Context of CVD

Current HIV treatment recommendations emphasize the importance of CVD risk screening in all patients starting ART and throughout the course of treatment.91, 92 Fasting lipid levels should be obtained at initiation of care for HIV-infected subjects and before and within 1 to 3 months after starting ART.91 In addition, screening for other metabolic abnormalities should also be performed. For example, fasting blood glucose or hemoglobin A1c should be obtained before and within 1 to 3 months after

Summary

As the HIV population ages, it is important to prevent development of long-term comorbidities such as CVD. The mechanisms of atherosclerosis in HIV remain to be fully elucidated. Host, virus, immune deficiency, and ART factors have a major role in the increased risk for CVD in HIV and lipid changes may both be a consequence and a driver of these interactions (Fig. 2). During untreated HIV infection, lipid alterations are associated with the virus and its effects on the immune system. These are

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References (100)

  • C.J. Cohen et al.

    Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomised, non-inferiority trial

    Lancet

    (2011)
  • F. Raffi et al.

    Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study

    Lancet

    (2013)
  • P.E. Sax et al.

    Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks

    Lancet

    (2012)
  • H. Bjorkbacka et al.

    Emerging biomarkers and intervention targets for immune-modulation of atherosclerosis - a review of the experimental evidence

    Atherosclerosis

    (2013)
  • L.S. Graham et al.

    Oxidized lipids enhance RANKL production by T lymphocytes: implications for lipid-induced bone loss

    Clin Immunol

    (2009)
  • J.J. Eron et al.

    Switch to a raltegravir-based regimen versus continuation of a lopinavir-ritonavir-based regimen in stable HIV-infected patients with suppressed viraemia (SWITCHMRK 1 and 2): two multicentre, double-blind, randomised controlled trials

    Lancet

    (2010)
  • J.E. Sackoff et al.

    Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City

    Ann Intern Med

    (2006)
  • J.S. Currier et al.

    Epidemiological evidence for cardiovascular disease in HIV-infected patients and relationship to highly active antiretroviral therapy

    Circulation

    (2008)
  • V.A. Triant et al.

    Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease

    J Clin Endocrinol Metab

    (2007)
  • V.A. Triant et al.

    Association of C-reactive protein and HIV infection with acute myocardial infarction

    J Acquir Immune Defic Syndr

    (2009)
  • J.V. Baker et al.

    Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection

    J Acquir Immune Defic Syndr

    (2011)
  • W.M. El-Sadr et al.

    CD4+ count-guided interruption of antiretroviral treatment

    N Engl J Med

    (2006)
  • C. Grunfeld et al.

    Preclinical atherosclerosis due to HIV infection: carotid intima-medial thickness measurements from the FRAM study

    AIDS

    (2009)
  • J.V. Baker et al.

    Inflammation predicts changes in high-density lipoprotein particles and apolipoprotein A1 following initiation of antiretroviral therapy

    AIDS

    (2011)
  • A.I. Choi et al.

    Association between kidney function and albuminuria with cardiovascular events in HIV-infected persons

    Circulation

    (2010)
  • N. Friis-Moller et al.

    Predicting the risk of cardiovascular disease in HIV-infected patients: the data collection on adverse effects of anti-HIV drugs study

    Eur J Cardiovasc Prev Rehabil

    (2010)
  • D.A. Duprez et al.

    Inflammation, coagulation and cardiovascular disease in HIV-infected individuals

    PLoS One

    (2012)
  • R.C. Kaplan et al.

    Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment

    J Acquir Immune Defic Syndr

    (2012)
  • T. Kelesidis et al.

    Biomarkers of microbial translocation and macrophage activation: association with progression of subclinical atherosclerosis in HIV-1 infection

    J Infect Dis

    (2012)
  • T.H. Burdo et al.

    Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients

    J Infect Dis

    (2011)
  • S. Subramanian et al.

    Arterial inflammation in patients with HIV

    JAMA

    (2012)
  • E. Blodget et al.

    Relationship between microbial translocation and endothelial function in HIV infected patients

    PLoS One

    (2012)
  • J.M. Brenchley et al.

    Microbial translocation is a cause of systemic immune activation in chronic HIV infection

    Nat Med

    (2006)
  • N. Friis-Moller et al.

    Cardiovascular disease risk factors in HIV patients–association with antiretroviral therapy. Results from the DAD study

    AIDS

    (2003)
  • L. Egana-Gorrono et al.

    Impact of genetic factors on dyslipidemia in HIV-infected patients starting antiretroviral therapy

    AIDS

    (2013)
  • M.J. Nicholaou et al.

    HAART-associated dyslipidemia varies by biogeographical ancestry in the multicenter AIDS cohort study

    AIDS Res Hum Retroviruses

    (2013)
  • E. Cassol et al.

    Plasma metabolomics identifies lipid abnormalities linked to markers of inflammation, microbial translocation, and hepatic function in HIV patients receiving protease inhibitors

    BMC Infect Dis

    (2013)
  • C. Grunfeld et al.

    Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome

    J Clin Endocrinol Metab

    (1992)
  • Drozd DR, Nance RM, Delaney JA. et al. Lower CD4 Count and Higher Viral Load Are Associated With Increased Risk of...
  • S.A. Riddler et al.

    Impact of HIV infection and HAART on serum lipids in men

    JAMA

    (2003)
  • B. Enkhmaa et al.

    HIV disease activity as a modulator of lipoprotein(a) and allele-specific apolipoprotein(a) levels

    Arterioscler Thromb Vasc Biol

    (2013)
  • W. Khovidhunkit et al.

    Infection and inflammation-induced proatherogenic changes of lipoproteins

    J Infect Dis

    (2000)
  • A.V. Khera et al.

    Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis

    N Engl J Med

    (2011)
  • Z. Mujawar et al.

    Human immunodeficiency virus impairs reverse cholesterol transport from macrophages

    PLoS Biol

    (2006)
  • E.R. Feeney et al.

    The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation

    J Infect Dis

    (2013)
  • B.J. Van Lenten et al.

    Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell cocultures

    J Clin Invest

    (1995)
  • S. Grinspoon et al.

    Cardiovascular risk and body-fat abnormalities in HIV-infected adults

    N Engl J Med

    (2005)
  • P. Holvoet et al.

    Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome

    JAMA

    (2008)
  • R.H. Haubrich et al.

    Metabolic outcomes in a randomized trial of nucleoside, nonnucleoside and protease inhibitor-sparing regimens for initial HIV treatment

    AIDS

    (2009)
  • M. Navab et al.

    HDL and cardiovascular disease: atherogenic and atheroprotective mechanisms

    Nat Rev Cardiol

    (2011)
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      Participants in the doravirine group had mean decreases of less than 1 mg/dL of LDL and non-HDL cholesterol from baseline to 96 weeks, whereas those in the ritonavir-boosted darunavir group had mean increases of 14·0 mg/dL in LDL cholesterol and 17·7 mg/dL in non-HDL cholesterol. Because dyslipidaemia occurs in a large proportion of patients with HIV-1, it is important that antiretroviral medications do not exacerbate these conditions, especially for those already at high risk of cardiovascular disease.20 Doravirine has been shown to have few drug–drug interactions—including when co-administered with atorvastatin, a commonly prescribed statin—supporting its use in these patients.21–23

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    Disclosures: J.S. Currier: Received grant funds to UCLA from Merck. T. Kelesidis: None.

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