Canadian Journal of Cardiology

Stroke in HIV

Published:December 05, 2018DOI:


      Stroke is a heterogeneous disease in persons living with human immunodeficiency virus (HIV). HIV is thought to increase the risk of stroke through both HIV-related and traditional stroke risk factors, which vary with respect to the patient’s age and clinical characteristics. Numerous studies show that detectable viremia and immunosuppression increase the risk of stroke across all ages, whereas traditional risk factors are more common in the aging population with HIV. As persons living with HIV age and acquire traditional stroke risk factors, the prevalence of stroke will likely continue to increase. Large- and small-vessel disease are the most common causes of stroke, although it is important to evaluate for infectious etiology as well. Research regarding the management of stroke in patients with HIV is scant, and recommendations often parallel those for the general population. Treatment of HIV and effective reduction of traditional stroke risk factors is important to reduce the risk of stroke in persons living with HIV. Future research will help elucidate the pathophysiology of HIV and stroke risk, investigate sex differences in stroke risk, and evaluate the safety and benefits of standard stroke preventative measures and HIV-specific interventions in this population.


      L’accident vasculaire cérébral (AVC) est une maladie hétérogène chez les personnes vivant avec le virus de l’immunodéficience humaine (VIH). On pense que le VIH accroît le risque d’AVC par l’intermédiaire de facteurs de risques tant liés au VIH que traditionnels qui varient en fonction de l’âge et des caractéristiques cliniques du patient. De nombreuses études montrent que la virémie décelable et l’immunosuppression augmentent le risque d’AVC sans égard à l’âge, alors que les facteurs de risque traditionnels sont plus fréquents dans la population plus âgée infectée par le VIH. À mesure que les personnes vivant avec le VIH vieillissent et acquièrent des facteurs de risque d’AVC traditionnels, la prévalence de l’AVC est appelée à augmenter. Si les affections touchant les gros et les petits vaisseaux sont les causes les plus courantes d’AVC, il n’en demeure pas moins important d’évaluer aussi la possibilité d’une étiologie infectieuse. Les recherches sur la prise en charge de l’AVC chez les patients infectés par le VIH sont rares, et les recommandations sont souvent les mêmes que celles visant la population générale. Le traitement du VIH et la réduction réelle des facteurs de risque d’AVC traditionnels jouent un rôle important dans la réduction du risque d’AVC chez les personnes vivant avec le VIH. Les recherches futures contribueront à préciser la physiopathologie du VIH et du risque d’AVC, à analyser les différences entre les sexes quant au risque d’AVC et à évaluer l’innocuité et les effets bénéfiques des mesures standard de prévention de l’AVC et des interventions ciblant le VIH dans cette population.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Canadian Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Abdallah A.
        • Chang J.
        • O’Carroll C.
        • et al.
        Stroke in human immunodeficiency virus-infected individuals in Sub-Saharan Africa (SSA): a systematic review.
        J Stroke Cerebrovasc Dis. 2018; 27: 1828-1836
        • Gutierrez J.
        • Menshawy K.
        • Gonzalez M.
        • et al.
        Brain large artery inflammation associated with HIV and large artery remodeling.
        AIDS. 2016; 30: 415-423
        • Koethe J.
        • Jenkins C.
        • Lau B.
        • et al.
        • North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD)
        Rising obesity prevalence and weight gain among adults starting antiretroviral therapy in the United States and Canada.
        AIDS Res Hum Retroviruses. 2016; 32: 50-58
        • Vinikoor M.
        • Napravnik S.
        • Floris-Moore M.
        • et al.
        Incidence and clinical features of cerebrovascular disease among HIV-infected adults in the Southeastern United States.
        AIDS Res Hum Retroviruses. 2013; 29: 1068-1074
        • Ances B.
        • Bhatt A.
        • Vaida F.
        • et al.
        Role of metabolic syndrome components in human immunodeficiency virus–associated stroke.
        J Neurovirol. 2009; 15: 249-256
        • Benjamin L.
        • Khoo S.
        HIV infection and stroke.
        Handb Clin Neurol. 2018; 152: 187-200
        • Bogiatzi C.
        • Hackam D.
        • McLeod A.
        • Spence J.
        Secular trends in ischemic stroke subtypes and stroke risk factors.
        Stroke. 2014; 45: 3208-3213
        • Ortiz G.
        • Koch S.
        • Romano J.G.
        • Forteza A.M.
        • Rabinstein A.A.
        Mechanisms of ischemic stroke in HIV-infected patients.
        Neurology. 2007; 68: 1257-1261
        • Chapman A.
        Globalization, human rights, and the social determinants of health.
        Bioethics. 2009; 23: 97-111
        • BeLue R.
        • Okoror T.
        • Iwelunmor J.
        • et al.
        An overview of cardiovascular risk factor burden in sub-Saharan African Countries: a socio-cultural perspective.
        Global Health. 2009; 5: 10
        • Sobngwi E.
        • Mbanya J.
        • Unwin N.
        • et al.
        Exposure over the life course to an urban environment and its relation with obesity, diabetes, and hypertension in rural and urban Cameroon.
        Int J Epidemiol. 2004; 33: 769-776
        • Yeates K.
        • Lohfeld L.
        • Sleeth J.
        • et al.
        A global perspective on cardiovascular disease in vulnerable populations.
        Can J Cardiol. 2015; 31: 1081-1093
      1. The Gap Report: People Aged 50 Years and Older. UNAIDS, Geneva, Switzerland2014
        • Kieburtz K.
        • Eskin T.
        • Ketonen L.
        • Tuite M.
        Opportunistic cerebral vasculopathy and stroke in patients with the acquired immunodeficiency syndrome.
        Arch Neurol. 1993; 50: 430-432
        • Qureshi A.
        • Janssen R.
        • Karon J.
        • et al.
        Human immunodeficiency virus infection and stroke in young patients.
        Arch Neurol. 1997; 54: 1150-1153
        • Rasmussen L.
        • Engsig F.
        • Christensen H.
        • et al.
        Risk of cerebrovascular events in persons with and without HIV: a Danish nationwide population-based cohort study.
        AIDS. 2011; 25: 1637-1646
        • Gutierrez J.
        • Albuquerque A.
        • Falzon L.
        HIV infection as vascular risk: a systematic review of the literature and meta-analysis.
        PLoS One. 2017; 12e0176686
        • Chow F.
        • Bacchetti P.
        • Kim A.
        • Price R.
        • Hsue P.
        Effect of CD4+ cell count and viral suppression on risk of ischemic stroke in HIV infection.
        AIDS. 2014; 28: 2573-2577
        • Marcus J.
        • Leyden W.
        • Chao C.
        • et al.
        HIV infection and incidence of ischemic stroke.
        AIDS. 2014; 28: 1911-1919
        • Okeke N.L.
        • Hicks C.B.
        • McKellar M.S.
        • Fowler Jr., V.G.
        • Federspiel J.J.
        History of AIDS in HIV-infected patients is associated with higher in-hospital mortality following admission for acute myocardial infarction and stroke.
        J Infect Dis. 2016; 213: 1955-1961
        • Sico J.
        • Chang C.
        • So-Armah K.
        • et al.
        HIV status and the risk of ischemic stroke among men.
        Neurology. 2015; 84: 1933-1940
        • Bushnell C.
        • McCullough L.
        • Awad I.
        • et al.
        Guidelines for the prevention of stroke in women: a statement for healthcare professionals from the American Heart Association/American Stroke Association.
        Stroke. 2014; 45: 1545-1588
        • Womack J.
        • Chang C.
        • So-Armah K.
        • et al.
        HIV infection and cardiovascular disease in women.
        J Am Heart Assoc. 2014; 3e001035
        • Moulignier A.
        • Savatovsky J.
        • Assoumou L.
        • et al.
        Silent cerebral small-vessel disease is twice as prevalent in middle-aged individuals with well-controlled, combination antiretroviral therapy-treated human immunodeficiency virus (HIV) than in HIV-uninfected individuals.
        Clin Infect Dis. 2018; 66: 1762-1769
        • Chow F.
        • Regan S.
        • Feske S.
        • et al.
        Comparison of ischemic stroke incidence in HIV-infected and non-HIV-infected patients in a US health care system.
        J Acquir Immune Defic Syndr. 2012; 60: 351-358
        • Savès M.
        • Chêne G.
        • Ducimetière P.
        • et al.
        Risk factors for coronary heart disease in patients treated for human immunodeficiency virus infection compared with the general population.
        Clin Infect Dis. 2003; 37: 292-298
        • Chow F.
        • Wilson M.
        • Wu K.
        • et al.
        Stroke incidence is highest in women and non-Hispanic blacks living with HIV in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort.
        AIDS. 2018; 32: 1125-1135
        • Chow F.
        • Regan S.
        • Zanni M.
        • et al.
        Elevated ischemic stroke risk among women living with HIV infection.
        AIDS. 2018; 32: 59-67
      2. Tirschwell D, Chow F, Becker K, et al. Incidence of stroke in the US Center for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) Cohort. Abstract presented at: 69th Annual American Academy of Neurology Meeting, April 22-28, 2017, Boston, Massachusetts.

        • Stone L.
        • Looby S.
        • Zanni M.
        Cardiovascular disease risk among women living with HIV in North America and Europe.
        Curr Opin HIV AIDS. 2017; 12: 585-593
        • Johnson W.
        • Onuma O.
        • Owolabi M.
        • Sachdev S.
        Stroke: a global response is needed.
        Bull World Health Organ. 2016; 94 (634-634A)
        • Mlay M.
        • Bakari M.
        The prevalence of HIV among patients admitted with stroke at the Muhimbili National Hospital, Dar es Salaam, Tanzania.
        Tanzan J Health Res. 2010; 12: 1-12
        • Benjamin L.
        • Allain T.
        • Mzinganjira H.
        • et al.
        The role of human immunodeficiency virus-associated vasculopathy in the etiology of stroke.
        J Infect Dis. 2017; 216: 545-553
        • Feinstein M.
        • Bogorodskaya M.
        • Bloomfield G.
        • et al.
        Cardiovascular complications of HIV in endemic countries.
        Curr Cardiol Rep. 2016; 18: 113
        • Sabin C.
        • Ryom L.
        • De Wit S.
        • et al.
        • D:A:D Study Group
        Associations between immune depression and cardiovascular events in HIV infection.
        AIDS. 2013; 27: 2735-2748
        • Bavinger C.
        • Bendavid E.
        • Niehaus K.
        • et al.
        Risk of cardiovascular disease from antiretroviral therapy for HIV: a systematic review.
        PLoS One. 2013; 8e59551
        • Ryom L.
        • Lundgren J.
        • El-Sadr W.
        • et al.
        Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study.
        Lancet HIV. 2018; 5: e291-e300
        • Opsomer M.
        • Dimitrova D.
        • Verspeelt J.
        • et al.
        Evaluation of cardiovascular disease risk in HIV-1-Infected patients treated with darunavir.
        Drugs R D. 2018; : 199-210
        • Marconi V.
        • Duncan M.
        • So-Armah K.
        • et al.
        Bilirubin Is inversely associated with cardiovascular disease among HIV-positive and HIV-negative individuals in VACS (Veterans Aging Cohort Study).
        J Am Heart Assoc. 2018; 7
        • Monforte A.
        • Reiss P.
        • Ryom L.
        • et al.
        Atazanavir is not associated with an increased risk of cardio- or cerebrovascular disease events.
        AIDS. 2013; 27: 407-415
        • LaFleur J.
        • Bress A.
        • Rosenblatt L.
        • et al.
        Cardiovascular outcomes among HIV-infected veterans receiving atazanavir.
        AIDS. 2017; 31: 2095-2106
        • Stein J.
        • Ribaudo H.
        • Hodis H.
        • et al.
        A prospective, randomized clinical trial of antiretroviral therapies on carotid wall thickness.
        AIDS. 2015; 29: 1775-1783
        • Desai M.
        • Joyce V.
        • Bendavid E.
        • et al.
        Risk of cardiovascular events associated with current exposure to HIV antiretroviral therapies in a US veteran population.
        Clin Infect Dis. 2015; 61: 445-452
        • Bedimo R.
        • Westfall A.
        • Drechsler H.
        • Vidiella G.
        • Tebas P.
        Abacavir use and risk of acute myocardial infarction and cerebrovascular events in the highly active antiretroviral therapy era.
        Clin Infect Dis. 2011; 53: 84-91
        • Triant V.
        • Lee H.
        • Hadigan C.
        • Grinspoon S.
        Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease.
        J Clin Endocrinol Metab. 2007; 92: 2506-2512
        • Sanders J.
        • Steverson A.
        • Pawlowski A.
        • et al.
        Atrial arrhythmia prevalence and characteristics for human immunodeficiency virus-infected persons and matched uninfected controls.
        PLoS One. 2018; 13e0194754
        • Benjamin L.A.
        • Corbett E.L.
        • Connor M.D.
        • et al.
        HIV, antiretroviral treatment, hypertension, and stroke in Malawian adults: a case-control study.
        Neurology. 2016; 86: 324-333
      3. HIV Surveillance Report 2015: Diagnoses of HIV Infection in the United States and Dependent Areas. Centers for Disease Control and Prevention, Atlanta, GA2015
        • Chow F.
        • Price R.
        • Hsue P.
        • Kim A.
        Greater risk of stroke of undetermined etiology in a contemporary HIV-Infected cohort compared with uninfected individuals.
        J Stroke Cerebrovasc Dis. 2017; 26: 1154-1160
        • Corral I.
        • Quereda C.
        • Moreno A.
        • et al.
        Cerebrovascular ischemic events in HIV-1-infected patients receiving highly active antiretroviral therapy: incidence and risk factors.
        Cerebrovasc Dis. 2009; 27: 559-563
        • Gutierrez J.
        • Hatleberg C.
        • Evans H.
        • Yin M.
        Role of pre-stroke immunity in ischemic stroke mechanism among patients with HIV.
        AIDS Care. 2019; 31: 270-274
        • Silva-Pinto A.
        • Costa A.
        • Serrão R.
        • Sarmento A.
        • Abreu P.
        Ischaemic stroke in HIV-infected patients: a case-control study.
        HIV Med. 2016; 18: 214-219
        • Tipping B.
        • de Villiers L.
        • Candy S.
        • Wainwright H.
        Stroke caused by human immunodeficiency virus–associated intracranial large-vessel aneurysmal vasculopathy.
        Arch Neurol. 2006; 63: 1640-1642
        • Pugliese A.
        • Isnardi D.
        • Saini A.
        • et al.
        Impact of highly active antiretroviral therapy in HIV-positive patients with cardiac involvement.
        J Infect. 2000; 40: 282-284
        • Gleason B.
        • Mirembe G.
        • Namuyonga J.
        • et al.
        Prevalence of latent rheumatic heart disease among HIV-infected children in Kampala, Uganda.
        J Acquir Immune Defic Syndr. 2016; 71: 196-199
        • Miró J.
        • del Río A.
        • Mestres C.
        Infective endocarditis in intravenous drug abusers and HIV-1 infected patients.
        Infect Dis Clin North Am. 2002; 16: 273-295
        • Ling D.
        • Janjua N.
        • Wong S.
        • et al.
        Sexually transmitted infection trends among gay or bisexual men from a clinic-based sentinel surveillance system in British Columbia, Canada.
        Sex Transm Dis. 2015; 42: 153-159
        • Nguyen T.
        • Kohn R.
        • Ng R.
        • Philip S.
        • Cohen S.
        Historical and current trends in the epidemiology of early syphilis in San Francisco, 1955 to 2016.
        Sex Transm Dis. 2018; 45: S55-S62
        • Novak R.
        • Ghanem A.
        • Hart R.
        • et al.
        • HIV Outpatient Study Investigators
        Risk factors and incidence of syphilis in HIV-infected persons, the HIV Outpatient Study, 1999-2015.
        Clin Infect Dis. 2018; 67: 1750-1759
        • Vilela P.
        Acute stroke differential diagnosis: stroke mimics.
        Eur J Radiol. 2017; 96: 133-144
        • Stahl C.
        • Wideman C.
        • Spira T.
        • et al.
        Protein S deficiency in men with long-term human immunodeficiency virus infection.
        Blood. 1993; 81: 1801-1807
        • Vishnu P.
        • Aboulafia D.
        Haematological manifestations of human immune deficiency virus infection.
        Br J Haematol. 2015; 171: 695-709
        • Mochan A.
        • Modi M.
        • Modi G.
        Protein S deficiency in HIV associated ischaemic stroke: an epiphenomenon of HIV infection.
        J Neurol Neurosurg Psychiatr. 2005; 76: 1455-1456
        • Allie S.
        • Stanley A.
        • Bryer A.
        • Meiring M.
        • Combrinck M.
        High levels of von Willebrand factor and low levels of its cleaving protease, ADAMTS13, are associated with stroke in young HIV-infected patients.
        Int J Stroke. 2015; 10: 1294-1296
        • Benjamin L.A.
        • Bryer A.
        • Emsley H.C.
        • et al.
        HIV infection and stroke: current perspectives and future directions.
        Lancet Neurol. 2012; 11: 878-890
        • Goldstein D.
        • Timpone J.
        • Cupps T.
        HIV-associated intracranial aneurysmal vasculopathy in adults.
        J Rheumatol. 2010; 37: 226-233
        • Kossorotoff M.
        • Touzé E.
        • Godon-Hardy S.
        • et al.
        Cerebral vasculopathy with aneurysm formation in HIV-infected young adults.
        Neurology. 2006; 66: 1121-1122
        • AbdelRazek M.
        • Gutierrez J.
        • Mampre D.
        • et al.
        Intravenous thrombolysis for stroke and presumed stroke in human immunodeficiency virus-infected adults: a retrospective, multicenter US study.
        Stroke. 2018; 49: 228-231
        • Carballo D.
        • Delhumeau C.
        • Carballo S.
        • et al.
        Increased mortality after a first myocardial infarction in human immunodeficiency virus-infected patients; a nested cohort study.
        AIDS Res Ther. 2015; 12: 4
        • Chow F.
        HIV infection, vascular disease, and stroke.
        Semin Neurol. 2014; 34: 35-46
        • Edwards N.J.
        • Grill M.F.
        • Choi H.A.
        • Ko N.U.
        Frequency and risk factors for cerebral arterial disease in a HIV/AIDS neuroimaging cohort.
        Cerebrovasc Dis. 2016; 41: 170-176
        • Sweeney E.
        • Thakur K.
        • Lyons J.
        • et al.
        Outcomes of intravenous tissue plasminogen activator for acute ischaemic stroke in HIV-infected adults.
        Eur J Neurol. 2014; 21: 1394-1399
      4. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Department of Health and Human Services. Available at: Accessed September 5, 2018.

        • Suchindran S.
        • Regan S.
        • Meigs J.
        • Grinspoon S.
        • Triant V.
        aspirin use for primary and secondary prevention in human immunodeficiency virus (HIV)-infected and HIV-uninfected patients.
        Open Forum Infect Dis. 2014; 1: ofu076
        • O’Brien M.
        • Montenont E.
        • Hu L.
        • et al.
        Aspirin attenuates platelet activation and immune activation in HIV-1-infected subjects on antiretroviral therapy: a pilot study.
        J Acquir Immune Defic Syndr. 2013; 63: 280-288
        • O’Brien M.
        • Hunt P.
        • Kitch D.
        • et al.
        A randomized placebo controlled trial of aspirin effects on immune activation in chronically human immunodeficiency virus-infected adults on virologically suppressive antiretroviral therapy.
        Open Forum Infect Dis. 2017; 4: ofw278
        • Funderburg N.
        • Jiang Y.
        • Debanne S.
        • et al.
        Rosuvastatin reduces vascular inflammation and T-cell and monocyte activation in HIV-infected subjects on antiretroviral therapy.
        J Acquir Immune Defic Syndr. 2015; 68: 396-404
      5. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29. Identifier NCT02344290, Evaluating the Use of Pitavastatin to Reduce the Risk of Cardiovascular Disease in HIV-Infected Adults (REPRIEVE); 2015 Jan 22. Available at: Accessed September 5, 2018.

        • Kim P.
        • Woods C.
        • Georgoff P.
        • et al.
        A1C underestimates glycemia in HIV infection.
        Diabetes Care. 2009; 32: 1591-1593
        • Monroe A.
        • Glesby M.
        • Brown T.
        Diagnosing and managing diabetes in HIV-infected patients: current concepts.
        Clin Infect Dis. 2015; 60: 453-462
        • Stein L.
        • Urban M.
        • Weber M.
        • et al.
        Effects of tobacco smoking on cancer and cardiovascular disease in urban black South Africans.
        Br J Cancer. 2008; 98: 1586-1592
        • Crothers K.
        • Goulet J.
        • Rodriguez-Barradas M.
        • et al.
        Decreased awareness of current smoking among health care providers of HIV-positive compared to HIV-negative veterans.
        J Gen Intern Med. 2007; 22: 749-754
        • Fitch K.
        • Anderson E.
        • Hubbard J.
        • et al.
        Effects of a lifestyle modification program in HIV-infected patients with the metabolic syndrome.
        AIDS. 2006; 20: 1843-1850