HIV y Riesgo Cardiovascular

HIV y Riesgo Cardiovascular. Dra. Magalí Barchuk Laboratorio de Lípidos y Aterosclerosis. Facultad de Farmacia y Bioquímica, UBA. 2021.

Infección por HIV. O o.

350/0 de dlsrn1nuclOn dc las nuevas Infccclones por VIH 20 420/0 de dlsrnlnucbn de las muertcs relaclonadas con el slda desde el Punto maxJmo de 204 580/0 de dlsrnlnuclön de nuevas Infecclones e/ VIH entre los n nos desde el 200) de aurnento del acceso al tratamlento antlrretrovirlco desde el m 10.

HIV en números. Argentina. actualizadcs a 2019 • a.mb:rs • Varones • En promedio se notifican se estiman 139 mil con VIH 17 desconoce diagnOstico 83 5.800 RazOn varön/ muJer en diagnösticos de VIH 2016 •2018 casos de VIH por aho Mediana de edad de diagnöstico de VIH 59 VIH Se en tratamientO Con antirretrovirales en el subsistema de Salud hasta diciembre de 2019. 32 anos 33 anos.

Terapia Antirretroviral. Abacavir Zidovudna. Efavirenz Neviparina.

Hígado graso. Madre: IAM Padre: HTA. Octubre 2008: derivado al servicio de infectologÍa por dermopatía  Diagnóstico de HIV.

Le indican Dieta. Se inicia tratamiento antirretroviral con: ritonavir (IP) Zidovudina (AZT,ITRN) Efavirenz (EFV, ITRNN).

Enfermedad renal. Cocaína. HIV-associated inflammation Insulin resistance Specific antiretroviral drugs Dyslipidemia HIV direct viral effect Lifestyle.

Traditional Risk Factors t Smoking t Hypertension t Diabetes HDL IV Drug Use Protease Inhibitor Use Opportunistic Infections Immune Dysfunction Inflammation Gut Microbiota Dysbiosis Neutrophil Extracellular Traps Microvascular Dysfunction Endothelial Dysfunction Thrombosis Plaque Rupture Plaque Erosion Coronary Artery Disease STEMI NSTEMI Recurrent MI Type II MI.

Le indican Dieta + fenofibrato. 01/2009 06/2009 08/2009 Hemograma Hematocrito (%)/ Rto Blancos/Plaquetas ( cel /mm 3 ) 47/ 4700 39/4900/327000 Urea (mg/dl) Creatinina (mg/dl) 35 0.8 36 1.35 Glucemia (mg/dl) 90 87 113 Col-Total (mg/dl) Col-HDL (mg/dl) Col-LDL (mg/dl) 150 226 199 29 166 TG (mg/dl) 275 793 420 FAL (UI/l) 180 256 TGO (UI/l) TGP (UI/l) 42 75 17 26 29 51 CD4 ( cel /mm 3 ) CV (copias/ml) 17 9100 41 menor a 40.

12/2009 Es derivado por el servicio de infectología por dislipemia en tratamiento con fenofibrato Refiere una disminución de grasa corporal en cara, pectorales, glúteos y abdomen Peso: 71.8 kg; Talla: 1.69 mts ; Cintura: 99 cm, BMI: 25. Laboratorio: glucemia 118 mg/dl CT 189 mg/dl HDL 50 mg/dl LDL 88 mg/dl TG 241 mg/dl TG/HDL 4.8 Se solicita PTOG glucemia basal: 119 mg/dl glucemia 120 min: 158 mg/dl Continua con fenofibrato Se dan indicaciones de Plan de alimentación más actividad física.

Por CD4 < 100 se rota TAR a Kaletra (IP) , Lopinavir, Ritonavir + 3TC (ITRN).

ART & HIV virus Immune activation Viral replication O o HIV CMV T cel Etivatbn (C038+) T znesænce (C028- / CD57+) Resistan ' Adipose Tissue O and Liver Dysfunction $4' visceral, epicardial fat, steatosis A#ocytes FARM, Admredin Glucose •.t*e HDLc, TNFa, PA-I, IL6 FFA Pathophysiology of CAD in IV-infected subjects sosclerosis Vascular and endothelial dysfunction z • Environment Chronic inflammation Inflammaging LPS I Macn*ages + others CRP.TVc, L6. sCD14 dOders Ddi-ners. trigen F. VII. Wilettand fadcc Tsue fadr, PtaBets HIV ART Endottwlial cells and VSMC Prelatnin A acarnulation ROS, RAS NO.

Actividad alterada de Lipasas. Inflamación in situ y sistémica.

Chronic inflammation o Inflammaging Mactial tanslces:n LPS Mactc#ages + others CRP,TtFa, u, sCD14 CoagulaS:n Seders Ddmets, ftrrgen Tsue fadm PlaEets reæfiity.

HIV-I Infected CDC T HIV-I 1 Macrophagø Gut epithelial barrier EV cargo TAR mRNA' RNA 2 Circulating EVs Cytokines 3 miRNA' C) a Cytokines Ctwmokinw Bystander 4 TNF.a IL-lß Figure I. Model of chronic inflammation enhanced by extracellular vesides. HIV replication or Of viral latently infected cels, in with bacterial PAMPs released into circulation as a consequence of microbial in the gut, constitute a stimuli for immune cells such as T ymphocytes, monocytes and These activated cells release Wito circulation EVs containing pro-inflarrrnatory from the host or HIV-denved PAMPs (as detaikd in the veskk) Macrophages exposed to circulating EVs become and rekase inflammatory cytokines (31. which in turn contrbute a positWe Imp of systemk chronic infbrnmatbn [41..

Promoción de la aterosclerosis y aumento de rigidez vascular, en ausencia de replicación viral (1-5).

Moléculas de adhesión Factores de crecimiento (angiogénesis, MLV).

ART & HIV virus Immune activation Viral replication O o HIV CMV T cel activatbn (C038+) T senesænce (CD28- / C057+) Resistan ' Adipose Tissue O and Liver Dysfunction $4' visceral, epicardial fat, steatosis A#ocytes FARM, Adporedin Gluoose •.t*e HDLc, TNFa, PA-I, IL6 FFA Pathophysiology of CAD in IV-infected subjects sosclerosis Vascular and endothelial dysfunction z • Environment Chronic inflammation Inflammaging LPS I Macn*ages + others CRP.TVc, L6. sCD14 Coagulasm dOders Ddi-ners. ftmo•gen F. VII. Wilettand fadcc Tsue fadr, PtaBets reæfiO HIV ART Endottwlial cells and VSMC Prelatnin A acarnulation Senescenæ ROS, RAS NO.

Endothelial dysfunction, arterial stiffening, and intima-media thickening in large arteries from HIV-I transgenic mice Laura Hansen 1, Ivana Parker2, Roy L. Sutliff3, Manu O. Piatt 1.4, and Rudolph Gleason Jr...

> Progreso de la enfermedad. Perfil de citoquinas alterado Clearance de lípidos Sintesis de VLDL.

Transl Res. 2017 May;183:41-56.

IP. Lipodistrofia, Obesidad Central, Hipertrofia mamaria e IR. Acumulación de ApoE y ApoCIII.

Table 1 Drugs Interest/cautionary for agents in HIV Metformin Sulfonylurus Glucagon-like peptide I Peptidase 4 (DPP4) inhibitors Gliflozins No weight gain Ihs interfere with antiretroviral treatment Redtre inflammatory markers such as TNF01pha HDL Weight ICN No in CIM or HIV RNA counts in treated HIV-infected No interactions ART and dapagliflozin are expwted Wamings and precautions with dolutegravir rnetformin concentration Weight Gain Weight Gain Should reduced when used in with P450 3A4/5 inhibitors swh as ritonavir Cangliflozin rmst itrreased when with ritonavir.

Curr Opin Cardiol. 2018 Jul;33(4):429-435. Transl Res. 2017 May;183:41-56.

Lipogénesis y diferenciación del adipocito. IP. Tejido Adiposo Visceral Central y Ácidos Grasos circulantes Oxidación de AG.

Además, los ATRV tendrían otros efectos que promoverían el proceso aterosclerótico y la enfermedad coronaria, por alteraciones de la.

12/2009 Es derivado por el servicio de infectología por dislipemia en tratamiento con fenofibrato Refiere una disminución de grasa corporal en cara, pectorales, glúteos y abdomen  Peso: 71.8 kg; Talla: 1.69 mts ; Cintura: 99 cm, BMI: 25. Laboratorio: glucemia 118 mg/dl CT 189 mg/dl HDL 50 mg/dl LDL 88 mg/dl TG 241 mg/dl TG/HDL 4.8 Se solicita PTOG glucemia basal: 119 mg/dl glucemia 120 min: 158 mg/dl Continua con fenofibrato Se dan indicaciones de Plan de alimentación más actividad física.

Hereditarias Adquiridas. Generalizadas Parciales.

TNF α α 2microglobulina PGC-1a. COX2 COX4 UCP12 CEBP-a PPAR γ GLUT4 LPL Leptina Adiponectina.

Lipodistrofia asociada a VIH.

2/2012 52 años de edad Refiere internación en UCO por IAM de cara anterior con colocación de 2 stent Glu basal: 112 mg/dl Glu 120 min: 182 mg/dl Insulinemia basal: 13.8 μ UI/l HOMA: 3.8 Peso: 74 Kg, BMI: 26.4 TA: 135/80 mmHg Se refuerzan las medidas higiénico-dietéticas Rosuvastatina 10 mg/d post IAM.

1. Epicardial Coronary Artery Disease Innuenced by chronic risk factors: HIV-related immune inflammation, dyslipidemia, hypertension, smoking. diabetes. dysbiosis & bacterial transkxat.on 2. In-Situ Thrombus, Ischemia, due to Plaque Plaque Rupture, or Vasospasm Influenced by HIV-associated coagulable milieu, persistent Inflammation. vascx:onstricbon 3. Downstream Complications: MI, myocardial scar, heart failure, fatal arrhythmias Influenæd by dynarnic factors: extent Of thrombus, microvascular function (likely impaired in HIV), collateral circulation. immune regulation & inflammatory cell clearance Figtre I. Pathcvhysiolcgy of human immmo&ficiercy virus (HIV)-assæiated coronary artery disease (CAD) arui acute corma•y yndrorre (A(S). MI, rnyocardal infarctim..

2/2012 52 años de edad Refiere internación en UCO por IAM de cara anterior con colocación de 2 stent Glu basal: 112 mg/dl Glu 120 min: 182 mg/dl Insulinemia basal: 13.8 μ UI/l HOMA: 3.8 Peso: 74 Kg, BMI: 26.4 TA: 135/80 mmHg Se refuerzan las medidas higiénico-dietéticas Rosuvastatina 10 mg/d post IAM.

Efectos Inmunomoduladores de las Estatinas. • Coenzyme QI O • Dolichol Steroids Cholesterol Oxisterols Acetyl-CoA Acetoacetyl-CoA HMG.CoA HMG-CoA ns reductase Mevalonate Isogw1tenyl-PP GPP FPP Squalene • Antioxidant activity • Antiinflammatory activity • Immunomodulatcry activity GGPP prenylates proteins (RhoA FPP prenylates proteins (Ras) Pleiotropic Effects Vascular- Protection Neuro- rotectio.

C' 2016 British HIV Association DO': 10.1 1 /hiv.12362 mv Medicine (2016) ORIGINAL RESEARCH Rosuvastatin vs. protease inhibitor switching for hypercholesterolaemia: a randomized trial FJ Lee, P Monteiro,2 D Baker, 3 M Bloch, 4 N Roth,5 R Finlayson, 6 R Moore,7 J Hoy,a E Martinez2 and A Carri 'Clinical Research Program. Centre for Applied Nfedical Research. St Vincent's Hospital. Sydney. NSW, Australia. 2 Infectious Diseases Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain, 'East Sydney Doctors, Sydney, NSW. Australia. CH01dsworth House Aledical Practice. Sydney. NSW. Australia. S Prahran Market Clinic. Melbourne. Vic.. Australia. 6Taylor Square Private Clinic. Sydney. NSW. Australia. 7 Northside Clinic. Melbourne, Vic„ Australia. a Department of Infectious Diseases, "Ille Alfred Hospital Monash University. Melbourne. Vice, Australia and 9 Sydney Medical School, University of Sydney, Sydney, NSW, Australia.

Resultado de imagen para imagen duda.

Lipodistrofia: Cirugía. Control glucémico estricto.

Innate immuntv: • Reduced GI mucosal integrity • Higher microbial translocation Villous blunting and local inflammation • Lower secretory IgA Lower eosinophils and NK ælls Adaptive immunity: • Lower total lymphocytes • Reduced T cell proliferative response Higher TH2-type CD4+ cell polarization • Lower THI cell IL-2 and INF-y expression • Impaired delayed hypersensitivity resgx)nse Potential interventions: Foa:i assistance / macronutrient supplements • Livelihood support / cash transfers • Clean water & programs to reduce environmental Expanded HIV testing and earlier treatment Innate immunitv: Higher circulating IL-6 and other cytokines produced by adipæytes MI inflammatory macrophage and T 17 CD.4+ T cell plarization in tissue Leptin (adipokine) promotes macrophage TNF-a, IL-6 and IL-12 expression Adaptive immunity: More robust CD4+ cell recovery on antiretroviral therapy at higher BMI • Increased peripheral T cells, T cell activation, and T HI-type CD4+ cell polarization Leptin (an adipokine produced by adipocytes) promdes CD4+ T cell proliferation and THI polarization in vitro Potential Interventions: • Weight loss and exercise programs • Gastric Growth-hormone-releasing hormone (Tesamorelin) Figure I. Malnutrition and obesity-related factors potentially affecting chronic immune ætivation inhuman immunodeficiency virus (HIV) infection. Abbreviations: BMI, mass index; Gl, gastrointestinal: IFNI, interferon y; IgA immunoglobulin A; IL, interleukin: NK natural killer: TNFO, tumor fætor.

Table 3. Comparisons of typical aging and aging with HIV — diseases and conditions Factor Vascular diseases Cancer (common) Cancer (environmental) Cancer (AIDS) Cancer (HIV) Renal Frailty Geriatric syndromes [kpression Hepatitis C Typical aging CVD, stroke hYRrtension Increased colon, prostate and breast Increased lung Kaposi sarcoma rare Anal, oral, Hodgkin's increased with age End stage due to diabetes and hypertension Loss of reserve frequent Vascular/Alzheimeds at old ages Falls/fractures common Less common with age (may related to decreased telomere length [461) Usual frequency HIV MI and CVD higher [48, 49] Less breast and prostate Increased lung Kaposi sarcoma associated with AIDS Anal, oral, at least 2-3 times higher [50] Immune activation is the cause [55] More frequent in MSM (12 vs. 9% in uninfected) [24]. In women associated with low CD4 nadir [21] Mild cognitive problems increased [56] Increased fracture risk with overall of 2.9 vs. I .8 patients with fractures Rr persons [53] 3-5 times rate of uninfected [541 Increased due to IV drug use Comment Both due to smoking.

Boccara F, et al. HIV and coronary heart disease : time for a better understanding . J Am Coll Cardiol . 2013 Feb 5;61(5):511-23. Chu C, et al. HIV-Associated Complications: A Systems-Based Approach . Am Fam Physician. 2017 Aug 1;96(3):161-169. Crowe SM, et al. The macrophage : the intersection between HIV infection and atherosclerosis . J Leukoc Biol 2010;87:589 –98. (4) Eckard AR, el at. Cardiovascular Disease, Statins, and HIV. J Infect Dis. 2016 Oct 1;214 Suppl 2:S83-92.. Garg A . Lipodystrophies : genetic and acquired body fat disorders . Clinical review . J Clin Endocrinol Metab . 2011 Nov;96(11):3313-25. Guaraldi G. Antiretroviral therapies and cardiovascular risk: True or false ? Atherosclerosis. 2017 May 27. pii : S0021-9150(17)30235-6 Sociedad Argentina de Infectologia . VI Consenso Argentino de Terapia Antirretroviral 2016-2017 . Buenos Aires, 2014-2015. Hansen L, et al. Endothelial dysfunction , arterial stiffening , and intima-media thickening in large arteries from HIV-1 transgenic mice . Ann Biomed Eng. 2013 Apr;41(4):682-93. Hsue PY, et al. Increased carotid intima-media thickness in HIV patients is associated with increased cytomegalovirus-specific T-cell responses . AIDS 2006;20:2275– 83. (1) Hsue PY, et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS 2009;23:1059–67. (3) Jain A, et al. HIV infection and lipids . Curr Opin Cardiol . 2018 Jul;33(4):429-435. Kaplan RC, et al. T cell activation and senescence predict subclinical carotid artery disease in HIV- infected women . J Infect Dis 2011;203:452– 63. (5) Kearns A. et al. HIV-1–Associated Atherosclerosis: Unraveling the Missing Link . J Am Coll Cardiol . 2017;69(25):3084-98 Koethe JR, et al. From Wasting to Obesity: The Contribution of Nutritional Status to Immune Activation in HIV Infection . J Infect Dis. 2016 Oct 1;214 Suppl 2:S75-82. Lee FJ, et al. Rosuvastatin vs. protease inhibitor switching for hypercholesterolaemia : a randomized trial . HIV Med. 2016 Sep;17(8):605-14. Maggi P, et al. Cardiovascular risk and dyslipidemia among persons living with HIV: a review . BMC Infect Dis. 2017 Aug 9;17(1):551. Ministerio de Salud y Seguridad Social. Dirección de SIDA, ETC, Hepatitis y TBC. Boletín sobre VIH, SIDA y ETS en Argentina , N°36, año XXII, diciembre 2019 Noubissi EC, et al. Diabetes and HIV. Curr Diab Rep. 2018 Oct 8;18(11):125. Non LR, et al. HIV and its relationship to insulin resistance and lipid abnormalities. Transl Res. 2017 May;183:41-56. Perez PS, et al . Extracellular vesicles and chronic inflammation during HIV infection. J Extracell Vesicles . 2019 Nov 6;8(1):1687275 Ross AC, et al. Relationship between inflammatory markers , endothelial activation markers , and carotid intima-media thickness in HIV- infected patients receiving antiretroviral therapy . Clin Infect Dis 2009;49:1119 –27. (2) Sinha A, et al. Coronary Artery Disease Manifestations in HIV: What, How, and Why. Can J Cardiol . 2019 Mar;35(3):270-279. Suelen Jorge Souzaa , et al. Lipid profile of HIV- infected patients in relation to antiretroviral therapy : a review . Ver Assoc Med Bras. 2013;59(2):186–198.

i 9>912949. Dra. Magalí Barchuk Lab. De Lípidos y Aterosclerosis Piso 1, Sector D – Hospital de Clínicas mbarchuk@docente.ffyb.uba.ar.