HIV and Stroke

Introduction

There is an elevated risk of ischemic stroke in human immunodeficiency virus (HIV)-infected compared to HIV-uninfected individuals, independent of age and traditional vascular risk factors. In individuals with untreated HIV infection, the odds of an ischemic stroke are more than five times greater than in uninfected individuals matched for age and sex . The risk is highest in the setting of worse virological control, low CD4 cell counts, and, particularly, short duration on treatment. The increased risk of stroke persists, but appears to taper off over years, after combination antiretroviral therapy (cART) is initiated. This suggests that an immune reconstitution inflammatory syndrome may be a contributing factor. Large, prospective studies comparing HIV-infected individuals on cART with controls have shown that HIV infection is associated with a 17–40% overall increase in the risk of ischemic stroke, after matching for traditional vascular risk factors and demographics .

In addition, the use of certain antiretroviral therapies, such as older protease inhibitors and abacavir, may increase this risk; however, the effects of cART, both short and long term, on cerebrovascular risk are not yet clear.

Causes of Stroke in HIV Infection

The most common causes or mechanisms cited for stroke development in HIV-infected patients are:

• cerebral infections,

• cardiac embolism,

• prothrombotic states,

• substance abuse,

• HIV-associated vasculopathies,

• accelerated atherosclerosis.

Cerebral Infections

Cerebral infections are important causes of secondary infective vasculitis and may cause both cerebral infarcts and hemorrhages. Some infections, such as syphilis or tuberculosis, may cause cerebral infarctions even in immunocompetent individuals. However, immunosuppressed people with HIV are more at risk of opportunistic infections, and a wider range of organisms have been associated with stroke in this setting. Stroke occurring in the weeks to months following cART initiation may be due to the immune reconstitution inflammatory syndrome either mounting a “paradoxical” response to antigen from a recent past infection in the host, or autoimmune target, or causing the “unmasking” of an occult central nervous system (CNS) opportunistic infection. Intracerebral hemorrhage has been documented in patients with infectious or neoplastic intracerebral space-occupying lesions such as primary CNS lymphoma, metastatic Kaposi’s sarcoma, and cerebral toxoplasmosis , and can mimic stroke. Selected cerebral infections that have been associated with stroke and vasculitis are listed in Table 124.1 .