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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.
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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.
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HIV replication, chronic inflammation and immune activation, and exposure to antiretroviral drugs (either directly or
Endocrinology and Metabolism Clinics of North America
Dyslipidemia and Cardiovascular Risk in Human Immunodeficiency Virus Infection
Section snippets
Key points
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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Cited by (35)
ApoA-I mimetics favorably impact cyclooxygenase 2 and bioactive lipids that may contribute to cardiometabolic syndrome in chronic treated HIV
2021, Metabolism: Clinical and ExperimentalCitation Excerpt :Altered lipids are associated with impaired immune responses, comorbidities and aging in people with chronic treated HIV [3,4]. Although dyslipidemia may reflect altered metabolism in HIV [5], certain bioactive lipids like fatty acids may directly contribute to insulin resistance and the pathogenesis of metabolic syndrome [6,7]. However, little is known about the impact of HIV-1 versus ART on bioactive lipids such as prostanoids, a family of lipid mediators generated by the action of cyclooxygenase (COX) on unsaturated fatty acids [8].
Cross-talk between lipid homeostasis and endoplasmic reticulum stress in neurodegeneration: Insights for HIV-1 associated neurocognitive disorders (HAND)
2020, Neurochemistry InternationalCitation Excerpt :In addition, the interpreted post-ART ER stress and UPR activation can provide a research model to examine the underlying pathways involved in dementia procedure and block the disease progression (Gills et al., 2007; Nooka and Ghorpade, 2017; Robertson et al., 2010; Schönthal, 2012). With regard to the functional significance of lipid composition in ER integrity and the common pathological features of HAND and other neurodegenerative disease, it is likely that targeting ART-elevated dyslipidemia and the mechanism by which they interact with PQC possess more beneficial outcomes (Dave et al., 2016; Feeney and Mallon, 2011; Kelesidis and Currier, 2014; Souza et al., 2013). As more than 90% of identified proteins and pathways in HIV-associated dementia and non-viral neurodegeneration overlap (Zhou et al., 2010), the findings of pathway studies can possibly be generalized to more than an individual disease.
Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial
2020, The Lancet HIVCitation Excerpt :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
NUtraceutical TReatment for hYpercholesterolemia in HIV-infected patients: The NU-TRY(HIV) randomized cross-over trial
2019, AtherosclerosisCitation Excerpt :Beyond traditional CV risk factor exposure, HIV infection per se, concomitant immunovirological abnormalities and ART have been shown to contribute to increased CV disease burden in this population [2]. Specifically, exposure to different ART regimens has been associated with proatherogenic lipid abnormalities [3], including hypercholesterolemia, hypertriglyceridemia and hypoalphalipoproteinemia [4]. Moreover, despite extensive ART-mediated virological suppression, residual HIV infection may still sustain chronic low-grade inflammation [5].
Disclosures: J.S. Currier: Received grant funds to UCLA from Merck. T. Kelesidis: None.