HIV Associated Risk Factors for Ischemic Stroke and Future Perspectives

Abstract

Although retroviral therapy (ART) has changed the HIV infection from a fatal event to a chronic disease, treated HIV patients demonstrate high prevalence of HIV associated comorbidities including cardio/cerebrovascular diseases. The incidence of stroke in HIV infected subjects is three times higher than that of uninfected controls. Several clinical and postmortem studies have documented the higher incidence of ischemic stroke in HIV infected patients. The etiology of stroke in HIV infected patients remains unknown; however, several factors such as coagulopathies, opportunistic infections, vascular abnormalities, atherosclerosis and diabetes can contribute to the pathogenesis of stroke. In addition, chronic administration of ART contributes to the increased risk of stroke in HIV infected patients. Concurrently, experimental studies in murine model of ischemic stroke demonstrated that HIV infection worsens stroke outcome, increases blood brain barrier permeability and increases neuroinflammation. Additionally, residual HIV viral proteins, such as Trans-Activator of Transcription, glycoprotein 120 and Negative regulatory factor, contribute to the pathogenesis. This review presents comprehensive information detailing the risk factors contributing to ischemic stroke in HIV infected patients. It also outlines experimental evidence demonstrating the impact of HIV infection on stroke outcomes, in addition to possible novel therapeutic approaches to improve these outcomes.

Commentary – HIV-Induced Extracranial Carotid Ectasia and Stroke

“…HIV is a known risk factor for both ischemic and hemorrhagic stroke. Even with the widespread use of antiretroviral therapy, stroke incidence is higher in patients with HIV compared to non-HIV control subjects [1]. Ischemic stroke in patients with HIV are often deemed to be cryptogenic, but several possible etiologies for stroke have been identified in this population, including coagulopathy, opportunistic infection, cardioembolism and vasculopathy [2,3].…”

“…Opportunistic infections, specifically varicella zoster, tuberculosis and neurosyphilis have also been implicated with stroke in the HIV population. There is thought to be a higher incidence of cardioembolism in patients with HIV, due to an increased risk of atrial fibrillation and cardiomyopathy, as well as endocarditis leading to septic emboli [1]. Finally, HIV vasculopathy, in the form of atherosclerotic and non-atherosclerotic disease as well as vasculitis, are known etiologies of stroke in this patient population via varied mechanisms.…”

“…Studies have worked to classify HIV vasculopathy into three subsets: 1) vasculitis, 2) accelerated atherosclerosis, and 3) nonatherosclerotic vasculopathy with intimal hyperplasia; although there is typically some overlap among these three mechanisms [3]. The pro-inflammatory state associated with HIV is thought to cause endothelial damage and intimal hyperplasia which contributes to accelerated atherosclerosis [1,2]. Non-atherosclerotic vasculopathy on the other hand, leads to vessel ectasia through vessel wall disruption and then subsequent thrombus formation.…”

“…In addition to the stroke etiologies described above, more recent studies have commented on the role of antiretroviral therapy (ART) in stroke pathogenesis in the HIV population. Specifically, prolonged use of protease inhibitors has been shown to be associated with dyslipidemia and therefore increased risk of stroke and other cardiovascular disease [1,2]. Several classes of ART drugs have also demonstrated potential to increase stroke risk by inducing endothelial toxicity and vascular dysfunction in HIV [1].…”

“…Specifically, prolonged use of protease inhibitors has been shown to be associated with dyslipidemia and therefore increased risk of stroke and other cardiovascular disease [1,2]. Several classes of ART drugs have also demonstrated potential to increase stroke risk by inducing endothelial toxicity and vascular dysfunction in HIV [1]. HIV itself is thought to alter blood brain barrier permeability as well, and certain ARTs may contribute to this further, promoting movement of viral infected and inflammatory cells into the CNS [1].…”