Human Immunodeficiency Virus (HIV) and Stroke Events: A Systematic Review and Meta Analysis


1 Cardiovascular Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

2 Health Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran


Stroke is a very disabling state that affects a considerable number of people around the world and it has been associated with human immunodeficiency (HIV) infection. However, there is no comprehensive review article in the literature that well investigates this critical topic. So, we performed this systematic review using Pubmed search. From 655 studies found at the initial search using broad Mesh terms and after exclusion studies of unrelated topics or out of criteria, 39 studies have been left and reviewed. During over 1.2 million person-years of follow up, a broad spectrum of incidence rate of stroke events has been reported by different authors from 0.73/1000 to 5.27/1000 person years of follow up in different cohort studies. About the anatomical regions of the brain which are complicated by HIV infection, circle of Willis and basal structures including basal ganglia and thalamus seem to be more affected. The range of risk factors which have been associated with stroke events in HIV infected patients is too much wide and includes controversy: younger age, gender,
hemorrhagic (vs. ischemic) stroke, antiretroviral therapy are the major factors with controversial factors associated with higher or lower stroke events in HIV infected individuals.on the other hand there were factors constantly repo rted as risk factors of higher stroke events in HIV positive patients which included CD4 cell counts, having AIDS, diabetes, being smoker, and not having arterial hypertension. Future controlled studies with large study populations can better clarify these risk factors.


  1. Centers for Disease Control and Prevention (CDC): Prevalence of disabilities and associated health conditions among adults –United States, 1999. MMWR Morb Mortal Wkly Rep 2001; 50: 120–125.
  2. Walker R, Whiting D, Unwin N. Stroke incidence in rural and urban Tanzania: a prospective, community based study. Lancet Neurol. 2010;9:786–792. [PubMed: 20609629]
  3. Emsley HCA, Hopkins SJ. Acute ischaemic stroke and infection: recent and emerging concepts.L ancet Neurol. 2008;7:341–353. [PubMed: 18339349]
  4. Karbasi-Afshar R, Izadi M. Human Immunodeficiency Virus (HIV) Infection and Coronary Artery Atherosclerotic Plaque Formation: A Systematic Review. Int J Travel Med Glob Health. (in press)
  5. Karbasi-Afshar R, Izadi M. Human Immunodeficiency Virus (HIV) and Cardiomyopathy: A Systematic Review. Int J Trav Med Glob Health. (in press)
  6. Ovbiagele B, Nath A. Increasing incidence of ischemic stroke in patients with HIV infection. Neurology. 2011 Feb 1;76(5):444-50. doi: 10.1212/WNL.0b013e31820a0cfc. reff118
  7. Cole JW, Pinto AN, Hebel JR, Buchholz DW, Earley CJ, Johnson CJ, Macko RF, Price TR, Sloan MA, Stern BJ, Wityk RJ, Wozniak MA, Kittner SJ. Acquired immunodeficiency syndrome and the risk of stroke. Stroke. 2004 Jan;35(1):51-6.
  8. Singer EJ, Valdes-Sueiras M, Commins DL, Yong W, Carlson M. HIV stroke risk: evidence and implications. Ther Adv Chronic Dis. 2013 Mar;4(2):61-70. doi:10.1177/2040622312471840. PubMed PMID: 23556125; PubMed Central PMCID: PMC3610259.
  9. Corral I, Quereda C, Moreno A, Pérez-Elías MJ, Dronda F, Casado JL, Muriel A, Masjuán J, Alonso-de-Leciñana M, Moreno S. Cerebrovascular ischemic events in HIV-1-infected patients receiving highly active antiretroviral therapy: incidence and risk factors. Cerebrovasc Dis. 2009;27(6):559-63. doi:10.1159/000214219. Reff181
  10. Vinikoor MJ, Napravnik S, Floris-Moore M, Wilson S, Huang DY, Eron JJ. Incidence and clinical features of cerebrovascular disease among HIV-infected adults in the Southeastern United States. AIDS Res Hum Retroviruses. 2013 Jul;29(7):1068-74. doi: 10.1089/AID.2012.0334. Reff10
  11. Sabin CA, Ryom L, Kovari H, Kirk O, de Wit S, Law M, Reiss P, Dabis F, Pradier C, El-Sadr W, Monforte AD, Kamara D, Phillips AN, Lundgren JD. Association Between ALT Level and the Rate of Cardio/Cerebrovascular Events in HIVPositive Individuals: The D: A: D Study. J Acquir Immune Defic Syndr. 2013 Aug 1;63(4):456-463. reff13
  12. Parruti G, Vadini F, Sozio F, Mazzott E, Ursini T, Polill E, Di Stefano P, Tontodonati M, Verrocchio MC, Fulcheri M, Calella G, Santilli F, Manzoli L. Psychological factors, including alexithymia, in the prediction of cardiovascular risk in HIV infected patients: results of a cohort study. PLoS One. 2013;8(1):e54555. doi: 10.1371/journal.pone.0054555. reff27
  13. Chow FC, Regan S, Feske S, Meigs JB, Grinspoon SK, Triant VA. 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 Aug 1;60(4):351-8. doi:10.1097/QAI.0b013e31825c7f24. reff67
  14. Durand M, Sheehy O, Baril JG, Lelorier J, Tremblay CL. Risk of Spontaneous Intracranial Hemorrhage in HIV-infected Individuals: A Population-based Cohort Study. J Stroke Cerebrovasc Dis. 2012 May 1. [Epub ahead of print] reff70
  15. Orlando G, Guaraldi G, Zona S, Carli F, Bagni P, Menozzi M, Cocchi S, Scaglioni R, Ligabue G, Raggi P. Ectopic fat is linked to prior cardiovascular events in men with HIV. J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):494-7. doi:10.1097/QAI.0b013e31824c8397. reff79
  16. Hasse B, Ledergerber B, Furrer H, Battegay M, Hirschel B, Cavassini M, Bertisch B, Bernasconi E, Weber R; Swiss HIV Cohort Study. Morbidity and aging in HIV-infected persons: the Swiss HIV cohort study. Clin Infect Dis. 2011 Dec;53(11):1130-9. doi: 10.1093/cid/cir626. reff94
  17. Bedimo RJ, Westfall AO, 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 Jul 1;53(1):84-91. doi:10.1093/cid/cir269. reff103
  18. Isezuo SA, Sani AZ, Ezunu E, Maiyaki S, Njoku CH, Obembe A. Clinical neuropathy in HIV/AIDS: an eight-year review of hospitalized patients in Sokoto, northwestern Nigeria. Trop Doct. 2009 Jul;39(3):133-5. doi: 10.1258/td.2008.080313.reff173
  19. Jowi JO, Mativo PM, Musoke SS. Clinical and laboratory characteristics of hospitalised patients with neurological manifestations of HIV/AIDS at the Nairobi hospital. East Afr Med J. 2007 Feb;84(2):67-76. Reff245
  20. d'Arminio A, Sabin CA, Phillips AN, Reiss P, Weber R, Kirk O, El-Sadr W, De Wit S, Mateu S, Petoumenos K, Dabis F, Pradier C, Morfeldt L, Lundgren JD, Friis-Møller N; Writing Committee of the D:A:D: Study Group. Cardio- and cerebrovascular events in HIV-infected persons. AIDS. 2004 Sep 3;18(13):1811-7. Reff330
  21. Evers S, Nabavi D, Rahmann A, Heese C, Reichelt D, Husstedt IW. Ischaemic cerebrovascular events in HIV infection: a cohort study. Cerebrovasc Dis. 2003;15(3):199-205. Reff376
  22. Connor MD, Lammie GA, Bell JE, Warlow CP, Simmonds P, Brettle RD. Cerebral infarction in adult AIDS patients: observations from the Edinburgh HIV Autopsy Cohort. Stroke. 2000 Sep;31(9):2117-26. Reff436
  23. Gillams AR, Allen E, Hrieb K, Venna N, Craven D, Carter AP. Cerebral infarction in patients with AIDS. AJNR Am J Neuroradiol. 1997 Sep;18(8):1581-5. REFF480
  24. Baily GG, Mandal BK. Recurrent transient neurological deficits in advanced HIV infection. AIDS. 1995 Jul;9(7):709-12. Reff510
  25. Perriëns JH, Mussa M, Luabeya MK, Kayembe K, Kapita B, Brown C, Piot P, Janssen R. Neurological complications of HIV-1-seropositive internal medicine inpatients in Kinshasa, Zaire. J Acquir Immune Defic Syndr. 1992;5(4):333-40. Reff582
  26. Rasmussen LD, Engsig FN, Christensen H, Gerstoft J, Kronborg G, Pedersen C, Obel N. Risk of cerebrovascular events in persons with and without HIV: a Danish nationwide population-based cohort study. AIDS. 2011 Aug 24;25(13):1637-46. doi: 10.1097/QAD.0b013e3283493fb0. reff601b
  27. Monforte Ad, Reiss P, Ryom L, El-Sadr W, Dabis F, De Wit S, Worm SW, Law MG, Weber R, Kirk O, Pradier C, Phillips AN, Lundgren JD, Sabin CA. Atazanavir is not associated with an increased risk of cardio- or cerebrovascular disease events. AIDS. 2013 Jan 28;27(3):407-15. doi:10.1097/QAD.0b013e32835b2ef1. Reff30
  28. Worm SW, Kamara DA, Reiss P, Fontas E, De Wit S, El-Sadr W, D'Arminio Monforte A, Law M, Phillips A, Ryom L, Dabis F, Weber R, Sabin C, Lundgren JD; D:A:D Study Group. Evaluation of HIV protease inhibitor use and the risk of sudden death or nonhemorrhagic stroke. J Infect Dis. 2012 Feb 15;205(4):535-9. doi: 10.1093/infdis/jir788. Reff84
  29. Qureshi AI, Janssen RS, Karon JM, Weissman JP, Akbar MS, Safdar K, Frankel MR. Human immunodeficiency virus infection and stroke in young patients. Arch Neurol. 1997 Sep;54(9):1150-3. Reff479
  30. Patsalides AD, Wood LV, Atac GK, Sandifer E, Butman JA, Patronas NJ. Cerebrovascular disease in HIV-infected pediatric patients: neuroimaging findings. AJR Am J Roentgenol. 2002 Oct;179(4):999-1003. reff391
  31. Philippet P, Blanche S, Sebag G, Rodesch G, Griscelli C, Tardieu M. Stroke and cerebral infarcts in children infected with human immunodeficiency virus. Arch Pediatr Adolesc Med. 1994 Sep;148(9):965-70. reff533
  32. Park YD, Belman AL, Kim TS, Kure K, Llena JF, Lantos G, Bernstein L, Dickson DW. Stroke in pediatric acquired immunodeficiency syndrome. Ann Neurol. 1990 Sep;28(3):303-11. reff600
  33. Izbudak I, Chalian M, Hutton N, Baskaran V, Jordan L, Siberry GK, Gailloud P, Agwu AL. Perinatally HIV-infected youth presenting with acute stroke: Progression/evolution of ischemic disease on neuroimaging. J Neuroradiol. 2013 Jul;40(3):172-80. doi: 10.1016/j.neurad.2012.08.001. Reff3
  34. Mateen FJ, Shinohara RT, Carone M, Miller EN, McArthur JC, Jacobson LP, Sacktor N; Multicenter AIDS Cohort Study (MACS) Investigators. Neurologic disorders incidence in HIV+ vs HIV- men: Multicenter AIDS Cohort Study, 1996-2011. Neurology. 2012 Oct 30;79(18):1873-80. doi:10.1212/WNL.0b013e318271f7b8. reff44
  35. Deshpande AK, Patnaik MM. Nonopportunistic neurologic manifestations of the human immunodeficiency virus: an Indian study. MedGenMed. 2005 Oct 4;7(4):2. Reff294
  36. Kumwenda JJ, Mateyu G, Kampondeni S, van Dam AP, van Lieshout L, Zijlstra EE. Differential diagnosis of stroke in a setting of high HIV prevalence in Blantyre, Malawi. Stroke. 2005 May;36(5):960-4. Reff324
  37. Mochan A, Modi M, Modi G. Stroke in black South African HIV-positive patients: a prospective analysis. Stroke. 2003 Jan;34(1):10-5. Reff382
  38. Góngora-Rivera F, Santos-Zambrano J, Moreno-Andrade T, Calzada-López P, Soto-Hernández JL. The clinical spectrum of neurological manifestations in AIDS patients in Mexico. Arch Med Res. 2000 Jul-Aug;31(4):393-8. [reff602b]
  39. Longo-Mbenza B, Longokolo Mashi M, Lelo Tshikwela M, Mokondjimobe E, Gombet T, Ellenga-Mbolla B, Nge Okwe A, Kangola Kabangu N, Mbungu Fuele S. Relationship between Younger Age, Autoimmunity, Cardiometabolic Risk, Oxidative Stress, HAART, and Ischemic Stroke in Africans with HIV/AIDS. ISRN Cardiol. 2011;2011:897908. doi:10.5402/2011/897908. Reff80
  40. Mlay M, Bakari M. The prevalence of HIV among patients admitted with stroke at the Muhimbili National Hospital, Dar es Salaam, Tanzania. Tanzania J Health Res. 2010;12(2): 105-113. REFF603B
  41. Lee B, Anekthananon T, Poungvarin N, Nilanont Y. Etiology and risk factors of stroke in HIV-infected patients in Siriraj Hospital: a case-control study. J Med Assoc Thai. 2012 Feb;95 Suppl 2:S227-34. Reff68
  42. Ances BM, Bhatt A, Vaida F, Rosario D, Alexander T, Marquie-Beck J, Ellis RJ, Letendre S, Grant I, McCutchan JA; HIV Neurobehavioral Research Center (HNRC) Group. Role of metabolic syndrome components in human immunodeficiency
  43. virus-associated stroke. J Neurovirol. 2009 May;15(3):249-56. doi: 10.1080/13550280902962443. Reff172
  44. Tipping B, de Villiers L, Wainwright H, Candy S, Bryer A. Stroke in patients with human immunodeficiency virus infection. J Neurol Neurosurg Psychiatry. 2007 Dec;78(12):1320-4. Reff254
  45. Ortiz G, Koch S, Romano JG, Forteza AM, Rabinstein AA. Mechanisms of ischemic stroke in HIV-infected patients. Neurology. 2007 Apr 17;68(16):1257-61. Reff258
  46. Heikinheimo T, Chimbayo D, Kumwenda JJ, Kampondeni S, Allain TJ. Stroke outcomes in Malawi, a country with high prevalence of HIV: a prospective follow-up study. PLoS One. 2012;7(3):e33765. doi: 10.1371/journal.pone.0033765. Reff77