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HOME > Cardiovasc Prev Pharmacother > Volume 4(3); 2022 > Article
Review Article Cardiovascular diseases in HIV patients
Hyun-Ha Changorcid
Cardiovascular Prevention and Pharmacotherapy 2022;4(3):95-98.
DOI: https://doi.org/10.36011/cpp.2022.4.e14
Published online: July 29, 2022
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Division of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, Daegu, Korea

Correspondence to Hyun-Ha Chang, MD Division of Infectious Diseases, Department of Internal Medicine, Kyungpook National University Hospital, Kyungpook National University School of Medicine, 130 Dongdeok-ro, Jung-gu, Daegu 41944, Korea. E-mail: changhha@knu.ac.kr
• Received: May 20, 2022   • Revised: July 8, 2022   • Accepted: July 18, 2022

Copyright © 2022 Korean Society of Cardiovascular Disease Prevention; Korean Society of Cardiovascular Pharmacotherapy.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

  • New and more effective antiretroviral therapy regimens have increased viral suppression and improved immune function recovery, leading to the extension of the lifespan of people living with HIV (PLWH). The extended lifespan of PLWH has recently been reported as a significant factor associated with diabetes mellitus, dyslipidemia, and long-term metabolic consequences, such as cardiovascular diseases. Therefore, this article briefly reviews the epidemiology and risk factors of cardiovascular diseases, including dyslipidemia and diabetes mellitus, in PLWH.
Although weight gain after initiation of antiretroviral therapy (ART) is thought to be appropriate and is considered part of the normal return to health following the successful suppression of HIV, excessive weight gain may lead to obesity and other negative metabolic consequences [1]. Metabolic syndrome is a cluster of risk factors for cardiovascular diseases (CVDs) and type 2 diabetes mellitus, primarily including abdominal obesity, atherogenic dyslipidemia, hypertension, hyperglycemia, insulin resistance, a proinflammatory state, and a prothrombotic state [2,3]. The global prevalence of metabolic syndrome among people living with HIV (PLWH) is from 16.7% to 31.3% according to a meta-analysis, possibly reflecting the extended lifespan of PLWH [4]. Obesity in PLWH results in increased inflammation, increased ectopic lipid disposition, and alterations in lipid and glucose metabolism, contributing to the development of CVDs [5]. CVDs, as long-term metabolic complications, have emerged as a new serious challenge in clinical settings. This review briefly describes the epidemiology and risk factors of CVDs in PLWH.
Before the introduction of highly active ART, Grunfeld et al. [6] reported that patients with HIV infection showed decreased total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels, but patients with AIDS, who have a blood CD4+ T cell count of less than 200/mm3 or have developed any opportunistic infections due to HIV infection, had elevated plasma triglyceride and free fatty acid levels. HIV is associated with chronic inflammation and immune activation, leading to decreased levels of total cholesterol and HDL-C and increased levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides [7,8]. A comprehensive review of the lipid profile as a risk factor for CVDs in PLWH in Asia reported that dyslipidemia was less prevalent in patients who first presented with HIV than in HIV-negative controls. In addition, total cholesterol levels were on average lower in HIV-positive patients, whereas findings were inconsistent regarding triglyceride levels [9]. That review also showed that ART had an unfavorable effect on plasma lipid levels in Asian PLWH [9].
HIV infection and highly active ART are associated with abnormalities of lipid metabolism [10]. ART regimens containing tenofovir disoproxil fumarate (TDF) are associated with lower lipid levels than those containing didanosine, zidovudine, stavudine, or abacavir [11,12]. TDF was recently replaced with tenofovir alafenamide because of the renal and bone toxicity of TDF, resulting in significant increases in triglyceride, total cholesterol, LDL-C, and HDL-C levels [13,14]. A prospective study investigating the incidence of dyslipidemia in PLWH reported that older nonnucleoside reverse transcriptase inhibitors, such as efavirenz and ritonavir-boosted protease inhibitors containing ARTs, were associated with a greater risk of dyslipidemia than newer agents from the same ART class. In addition, dyslipidemia was less common with integrase strand transfer inhibitors than with boosted protease inhibitors [15]. This report also found that, compared with dolutegravir, dyslipidemia was more common with elvitegravir/cobicistat and raltegravir but less common with rilpivirine [15]. Raltegravir, dolutegravir, and bictegravir were associated with more favorable lipid profiles than boosted protease inhibitors, efavirenz, and elvitegravir/cobicistat, in studies conducted on naive participants, and were associated with a clinically significant decrease in lipoproteins in studies of patients who switched regimens [16].
The established risk factors for type 2 diabetes mellitus are also common among PLWH, including older age, high body mass index, central adiposity, family history of diabetes, and Hispanic or African American ethnicity [1721]. Low CD4+ T cell counts and treatment regimens with older nucleoside/nucleotide reverse transcriptase inhibitors and protease inhibitors are additional risk factors for diabetes among PLWH [19,22]. The Veterans Aging Cohort Study found that the risk of diabetes mellitus according to weight gain among PLWH was greater than that in the general population [23]. PLWH had a lower prevalence of diabetes mellitus at baseline (12% in PLWH vs. 23% in HIV-negative individuals); however, the association between weight gain and the risk of diabetes mellitus was linear for PLWH and uninfected people, but the slope of the association was steeper for PLWH. For every 5 pounds (about 2.27 kg) of weight gained, PLWH were at a more sharply increased risk (14%) of developing diabetes mellitus than HIV-negative individuals (8%, P<0.01) [23]. Similar to HIV-negative people, PLWH with diabetes have a higher risk of CVD, chronic kidney disease, and mortality than those without diabetes [21]. A study using the Korean National Health Insurance Service (NHIS) claims database including 14,134 PLWH and 282,039 HIV-negative members of the general population from 2004 to 2016 reported that the incidence of diabetes mellitus was higher in PLWH than in the general population (10.4% in PLWH vs. 6.6% in the general population, P<0.001). Moreover, the incidence of diabetes mellitus was found to be higher in PLWH than in HIV-negative individuals at younger ages [24].
A recent systematic review reported that the risk of CVD development in PLWH was twice that of the general population, and the global burden of HIV-associated CVDs has tripled over the past two decades [25]. Triant et al. [26] reported that the difference in acute myocardial infarction rates between PLWH and non-HIV patients was significant, with a relative risk (RR) of 1.75 (95% confidence interval [CI], 1.51–2.02; P<0.0001), and the RRs (for HIV vs. non-HIV) were 2.98 (95% CI, 2.33–3.75; P<0.0001) for women and 1.40 (95% CI, 1.16–1.67; P=0.0003) for men, adjusting for age, sex, race, hypertension, diabetes, and dyslipidemia. Therefore, the authors suggested that acute myocardial infarction rates and cardiovascular risk factors were higher in HIV patients than in non-HIV patients, particularly among women, and that cardiac risk modification strategies might be important for the long-term care of PLWH [26].
Hsue et al. [27] reported that increased atherosclerosis with HIV infection could occur in the absence of ART, detectable viremia, or overt immunodeficiency, and suggested that chronic inflammation might account for early atherosclerosis in HIV patients. Furthermore, Nordell et al. [28] reported also that higher interleukin-6 and D-dimer levels, reflecting enhanced inflammation and coagulation associated with HIV, were associated with higher risks of fatal CVD and death after a nonfatal CVD event. The Data Collection on Adverse Events of Anti-HIV Drugs (DAD) found that the incidence of myocardial infarction increased with longer exposure to combination ART [29]. The DAD study showed that higher exposure to protease inhibitors was associated with a greater risk of myocardial infarction, which was partly explained by dyslipidemia [30]. This study also showed that patients exposed to abacavir and didanosine within the preceding 6 months had a higher risk of myocardial infarction, and the excess risk did not seem to be explained by underlying established cardiovascular risk factors and was not present beyond 6 months after drug cessation [31].
However, the contribution of obesity to the development of CVD in PLWH is not well understood. The DAD study reported that obesity contributed to CVD risk, showing that the RR of CVD for obese PLWH (body mass index, ≥30 kg/m2) compared with that for normal weight PLWH (body mass index, 23–25 kg/m2) was 1.31 (95% CI, 1.03–1.67) [17]. However, a study using the Korean NHIS claims database, including 14,134 PLWH and 282,039 HIV-negative members of the general population from 2004 to 2016, reported that the incidence of CVD among PLWH was lower than that in the general population in all age groups (1.4% vs. 3.1%, P<0.001), while the adjusted incidence ratios for CVD among PLWH increased over time [24]. Therefore, further long-term follow-up studies are necessary to clarify the relationship between CVD and HIV infection among Korean PLWH.
CVDs as long-term metabolic complications after the initiation of ART have emerged as a serious challenge in our HIV clinics. There have been no well-designed studies establishing the relationship between ART and the incidence of complications, such as CVDs, among Korean PLWH. Further large-scale, long-term follow-up cohort studies are needed to clarify the prevalence and risk factors of CVDs among Korean PLWH.

Ethical statements

Not applicable.

Conflicts of interest

The author has no conflicts of interest to declare.

Funding

None.

  • 1. Koethe JR, Lagathu C, Lake JE, Domingo P, Calmy A, Falutz J, et al. HIV and antiretroviral therapy-related fat alterations. Nat Rev Dis Primers 2020;6:48. ArticlePubMedPDF
  • 2. Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech 2009;2:231-7.ArticlePubMedPMCPDF
  • 3. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009;120:1640-5.ArticlePubMed
  • 4. Nguyen KA, Peer N, Mills EJ, Kengne AP. A meta-analysis of the metabolic syndrome prevalence in the global HIV-infected population. PLoS One 2016;11:e0150970.ArticlePubMedPMC
  • 5. Bailin SS, Gabriel CL, Wanjalla CN, Koethe JR. Obesity and weight gain in persons with HIV. Curr HIV/AIDS Rep 2020;17:138-50.ArticlePubMedPMCPDF
  • 6. Grunfeld C, Pang M, Doerrler W, Shigenaga JK, Jensen P, Feingold KR. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab 1992;74:1045-52.ArticlePubMed
  • 7. El-Sadr WM, Mullin CM, Carr A, Gibert C, Rappoport C, Visnegarwala F, et al. Effects of HIV disease on lipid, glucose and insulin levels: results from a large antiretroviral-naive cohort. HIV Med 2005;6:114-21.ArticlePubMed
  • 8. Funderburg NT, Mehta NN. Lipid abnormalities and inflammation in HIV inflection. Curr HIV/AIDS Rep 2016;13:218-25.ArticlePubMedPMCPDF
  • 9. Bijker R, Choi JY, Ditangco R, Kiertiburanakul S, Lee MP, Siwamogsatham S, et al. Cardiovascular disease and cardiovascular disease risk in HIV-positive populations in the Asian region. Open AIDS J 2017;11:52-66.ArticlePubMedPMCPDF
  • 10. Lo J. Dyslipidemia and lipid management in HIV-infected patients. Curr Opin Endocrinol Diabetes Obes 2011;18:144-7.ArticlePubMedPMC
  • 11. Crane HM, Grunfeld C, Willig JH, Mugavero MJ, Van Rompaey S, Moore R, et al. Impact of NRTIs on lipid levels among a large HIV-infected cohort initiating antiretroviral therapy in clinical care. AIDS 2011;25:185-95.ArticlePubMedPMC
  • 12. Valantin MA, Bittar R, de Truchis P, Bollens D, Slama L, Giral P, et al. Switching the nucleoside reverse transcriptase inhibitor backbone to tenofovir disoproxil fumarate + emtricitabine promptly improves triglycerides and low-density lipoprotein cholesterol in dyslipidaemic patients. J Antimicrob Chemother 2010;65:556-61.ArticlePubMed
  • 13. Plum PE, Maes N, Sauvage AS, Frippiat F, Meuris C, Uurlings F, et al. Impact of switch from tenofovir disoproxil fumarate-based regimens to tenofovir alafenamide-based regimens on lipid profile, weight gain and cardiovascular risk score in people living with HIV. BMC Infect Dis 2021;21:910. ArticlePubMedPMCPDF
  • 14. Lagoutte-Renosi J, Flammang M, Chirouze C, Beck-Wirth G, Bozon F, Brunel AS, et al. Real-life impact on lipid profile of a switch from tenofovir disoproxil fumarate to tenofovir alafenamide in HIV-infected patients. Curr HIV Res 2021;19:84-9.ArticlePubMedPDF
  • 15. The RESPOND Study Group. Incidence of dyslipidemia in people with HIV who are treated with integrase inhibitors versus other antiretroviral agents. AIDS 2021;35:869-82.ArticlePubMed
  • 16. Saumoy M, Sanchez-Quesada JL, Ordonez-Llanos J, Podzamczer D. Do all integrase strand transfer inhibitors have the same lipid profile? Review of randomised controlled trials in naive and switch scenarios in HIV-infected patients. J Clin Med 2021;10:3456. ArticlePubMedPMC
  • 17. Achhra AC, Sabin C, Ryom L, Hatleberg C, Antonella dʼAminio M, de Wit S, et al. Body mass index and the risk of serious non-AIDS events and all-cause mortality in treated HIV-positive individuals: D:A:D cohort analysis. J Acquir Immune Defic Syndr 2018;78:579-88.ArticlePubMed
  • 18. Nansseu JR, Bigna JJ, Kaze AD, Noubiap JJ. Incidence and risk factors for prediabetes and diabetes mellitus among HIV-infected adults on antiretroviral therapy: a systematic review and meta-analysis. Epidemiology 2018;29:431-41.ArticlePubMed
  • 19. Butt AA, McGinnis K, Rodriguez-Barradas MC, Crystal S, Simberkoff M, Goetz MB, et al. HIV infection and the risk of diabetes mellitus. AIDS 2009;23:1227-34.ArticlePubMedPMC
  • 20. Duncan AD, Goff LM, Peters BS. Type 2 diabetes prevalence and its risk factors in HIV: a cross-sectional study. PLoS One 2018;13:e0194199.ArticlePubMedPMC
  • 21. Putcharoen O, Wattanachanya L, Sophonphan J, Siwamogsatham S, Sapsirisavat V, Gatechompol S, et al. New-onset diabetes in HIV-treated adults: predictors, long-term renal and cardiovascular outcomes. AIDS 2017;31:1535-43.ArticlePubMed
  • 22. Brown TT, Cole SR, Li X, Kingsley LA, Palella FJ, Riddler SA, et al. Antiretroviral therapy and the prevalence and incidence of diabetes mellitus in the multicenter AIDS cohort study. Arch Intern Med 2005;165:1179-84.ArticlePubMed
  • 23. Herrin M, Tate JP, Akgun KM, Butt AA, Crothers K, Freiberg MS, et al. Weight gain and incident diabetes among HIV-infected veterans initiating antiretroviral therapy compared with uninfected individuals. J Acquir Immune Defic Syndr 2016;73:228-36.ArticlePubMedPMC
  • 24. Kim JH, Noh J, Kim W, Seong H, Kim JH, Lee WJ, et al. Trends of age-related non-communicable diseases in people living with HIV and comparison with uninfected controls: a nationwide population-based study in South Korea. HIV Med 2021;22:824-33.ArticlePubMedPDF
  • 25. Shah AS, Stelzle D, Lee KK, Beck EJ, Alam S, Clifford S, et al. Global burden of atherosclerotic cardiovascular disease in people living with HIV: systematic review and meta-analysis. Circulation 2018;138:1100-12.ArticlePubMedPMC
  • 26. Triant VA, Lee H, Hadigan C, Grinspoon SK. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 2007;92:2506-12.ArticlePubMedPMCPDF
  • 27. Hsue PY, Hunt PW, Schnell A, Kalapus SC, Hoh R, Ganz P, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS 2009;23:1059-67.ArticlePubMedPMC
  • 28. Nordell AD, McKenna M, Borges AH, Duprez D, Neuhaus J, Neaton JD, et al. Severity of cardiovascular disease outcomes among patients with HIV is related to markers of inflammation and coagulation. J Am Heart Assoc 2014;3:e000844.ArticlePubMedPMC
  • 29. Friis-Moller N, Weber R, Reiss P, Thiebaut R, Kirk O, d’Arminio Monforte A, et al. Cardiovascular disease risk factors in HIV patients: association with antiretroviral therapy: results from the DAD study. AIDS 2003;17:1179-93.ArticlePubMed
  • 30. DAD Study Group, Friis-Moller N, Reiss P, Sabin CA, Weber R, Monforte Ad, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007;356:1723-35.ArticlePubMed
  • 31. D:A:D Study Group, Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, et al. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet 2008;371:1417-26.ArticlePubMedPMC

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