HIV infection and stroke: current perspectives and future directions

Abstract

HIV infection can result in stroke via several mechanisms, including opportunistic infection, vasculopathy, cardioembolism, and coagulopathy. However, the occurrence of stroke and HIV infection might often be coincidental. HIV-associated vasculopathy describes various cerebrovascular changes, including stenosis and aneurysm formation, vasculitis, and accelerated atherosclerosis, and might be caused directly or indirectly by HIV infection, although the mechanisms are controversial. HIV and associated infections contribute to chronic inflammation. Combination antiretroviral therapies (cART) are clearly beneficial, but can be atherogenic and could increase stroke risk. cART can prolong life, increasing the size of the ageing population at risk of stroke. Stroke management and prevention should include identification and treatment of the specific cause of stroke and stroke risk factors, and judicious adjustment of the cART regimen. Epidemiological, clinical, biological, and autopsy studies of risk, the pathogenesis of HIV-associated vasculopathy (particularly of arterial endothelial damage), the long-term effects of cART, and ideal stroke treatment in patients with HIV are needed, as are antiretrovirals that are without vascular risk.

Figure 1

Aneurysmal HIV-associated vasculopathy (A) View of the ventral surface of the brain showing a thrombotic occlusion of the left internal carotid artery and evidence of vasculopathy of the left middle cerebral artery (arrows). (B) CT angiogram showing several fusiform aneurysms affecting the circle of Willis. (C) Haematoxylin and eosin stain of a cross-section through an aneurysmal cerebral artery showing evidence of intimal hyperplasia, fragmentation of internal elastic lamina (arrow), and neutrophil infiltrate; note the absence of atherosclerosis. Reproduced from Tipping and colleagues, by permission of the American Medical Association.

Figure 2

Hypotheses on the mechanism of HIV-associated vasculopathy Mechanisms are specific to atheroma and potentially applicable to the other forms of HIV-associated vasculopathy. (A) Direct damage can occur through continuous exposure of the endothelium to HIV virion or viral particles (eg, GP120 or TAT) leading to endothelial dysfunction. (B) Indirect damage can arise from circulating infected monocytes freely transmigrating the endothelium as part of a normal surveillance, with an impaired reverse transmigration, thus increasing the subendothelial population of HIV infected monocytes. The release of chemokines such as CCL2 from infected leucocytes attracts more leucocytes. (C) Several events lead to the progression of damage and propagation of atherogenesis: upregulation of cell adhesion molecules (eg, selectins), leading to increased adhesion of infected or non-infected leucocytes; release of HIV virions into the arterial smooth muscle and continued active replication of the virus in smooth muscle cells; inflammatory cytokine release from HIV-infected cells, leading to further recruitment and adhesion of leucocytes, increased production of reactive oxygen species, and derangement of the coagulation system, favouring a prothrombotic state. Underlying this continuing process is the remodelling of the vessel wall, involving intimal hyperplasia and fragmentation of the elastic lamina. (D) Thrombotic occlusion of the vessel wall lumen is one of the outcomes of this process.

Figure 3

Management approach for HIV-infected patients with stroke TIA=transient ischaemic attack. cART=combined antiretroviral therapy. FBC=full blood count. ESR=erythrocyte sedimentation rate. ANA=antinuclear antibodies. ANCA=antineutrophil cytoplasmic antibodies. HSV-1=herpes simplex virus type 1. VZV=varicella zoster virus. CMV=cytomegalovirus. TB=tuberculosis. ECG=electrocardiograph.