Varicella-zoster virus reactivation is frequently detected in HIV-infected individuals presenting with stroke.

Infections are an underappreciated cause of stroke, particularly in young and immunocompromised individuals. Varicella-zoster virus (VZV) reactivation, particularly ophthalmic zoster, has been linked to increased risk of stroke but diagnosing VZV-associated cerebral vasculopathy is challenging as neither a recent zoster rash, nor detectable levels of VZV DNA are universally present at stroke presentation. Detection of VZV IgG in cerebrospinal fluid (CSF-VZVG) presents a promising alternative, but requires evaluation of individual blood-CSF dynamics, particularly in the setting of chronic inflammatory states such as HIV infection. Consequently, its use has not been broadly adopted as simple diagnostic algorithms are not available. In this study looking at young adults presenting with acute stroke, we used an algorithm that includes testing for both VZV nucleic acids and CSF-VZVG which was corrected for blood-CSF barrier dynamics and poly-specific immune activation. We found that 13 of 35 (37%), including 7 with a positive CSF VZV PCR, young HIV-infected adults presenting with stroke, 3 of 34 (9%) young HIV-uninfected adults presenting with stroke, and 1 of 18 (6%) HIV-infected nonstroke controls demonstrated evidence of central nervous system reactivation of VZV.

Viral protein R polymorphisms in the pathogenesis of HIV-associated acute ischaemic stroke: a case-control study.

HIV-1 viral proteins have been implicated in endothelial dysfunction, which is a major determinant of ischaemic stroke risk in HIV-infected individuals. Polymorphisms in HIV-1 viral protein R (Vpr) may alter its potential to promote endothelial dysfunction, by modifying its effects on viral replication, reactivation of latent cells, upregulation of pro-inflammatory cytokines and infection of macrophages. We analysed Vpr polymorphisms and their association with acute ischaemic stroke by comparing Vpr signature amino acids between 54 HIV-infected individuals with acute ischaemic stroke, and 80 age-matched HIV-infected non-stroke controls. Isoleucine at position 22 and serine at position 41 were associated with ischaemic stroke in HIV. Individuals with stroke had lower CD4 counts and CD4 nadirs than controls. These polymorphisms are unique to individuals with stroke compared to South African subtype C and the control group consensus sequences. Signature Vpr polymorphisms are associated with acute ischaemic stroke in HIV. These may increase stroke risk by promoting endothelial dysfunction and susceptibility to opportunistic infections. Therapeutic targeting of HIV-1 viral proteins may present an additional mechanism of decreasing stroke risk in HIV-infected individuals.

Arterial ischemic stroke in HIV: Defining and classifying etiology for research studies.

HIV infection, and potentially its treatment, increases the risk of an arterial ischemic stroke. Multiple etiologies and lack of clear case definitions inhibit progress in this field. Several etiologies, many treatable, are relevant to HIV-related stroke. To fully understand the mechanisms and the terminology used, a robust classification algorithm to help ascribe the various etiologies is needed. This consensus paper considers the strengths and limitations of current case definitions in the context of HIV infection. The case definitions for the major etiologies in HIV-related strokes were refined (e.g., varicella zoster vasculopathy and antiphospholipid syndrome) and in some instances new case definitions were described (e.g., HIV-associated vasculopathy). These case definitions provided a framework for an algorithm to help assign a final diagnosis, and help classify the subtypes of HIV etiology in ischemic stroke.

High levels of von Willebrand factor and low levels of its cleaving protease, ADAMTS13, are associated with stroke in young HIV-infected patients.

BACKGROUND: Stroke associated with human immunodeficiency virus infection may occur through a variety of mechanisms. Von Willebrand factor is a marker of endothelial dysfunction, and is elevated in human immunodeficiency virus infection. High levels of von Willebrand factor, a protein involved in platelet adhesion and aggregation, and low levels of ADAMTS13, a metalloproteinase that cleaves von Willebrand factor, have been associated with an increased risk of thrombosis. AIM: To investigate the role of von Willebrand factor and ADAMTS13 in the pathogenesis of human immunodeficiency virus-related stroke in young patients. METHODS: A case-control study (n = 100) comprising three participant groups: human immunodeficiency virus-positive antiretroviral therapy-naïve young strokes (n = 20), human immunodeficiency virus-negative young strokes (n = 40), and human immunodeficiency virus-positive antiretroviral therapy-naïve nonstroke controls (n = 40). von Willebrand factor and ADAMTS13 levels were measured in plasma samples collected five- to seven-days poststroke. RESULTS: Human immunodeficiency virus-positive stroke participants had higher von Willebrand factor levels than human immunodeficiency virus-negative strokes (173·5% vs. 135%, P = 0·032). They tended to have higher levels of von Willebrand factor than human immunodeficiency virus-positive nonstroke controls (173·5% vs. 129%, P = 0·061). Human immunodeficiency virus-positive stroke participants had lower levels of ADAMTS13 than human immunodeficiency virus-positive nonstroke controls (0% vs. 23·5% P = 0·018) most likely due to the effect of the acute stroke. However, in the nonstroke group, these levels were significantly reduced compared with population norms. von Willebrand factor levels in all human immunodeficiency virus-positive participants were negatively correlated with CD4 counts. CONCLUSIONS: Stroke in human immunodeficiency virus infection is associated with a prothrombotic state, characterized by elevated von Willebrand factor and low ADAMTS13 levels.

The complexity of HIV vasculopathy.

We present a case and discuss stroke related to human immunodeficiency virus (HIV) infection and the difficulties of reaching a firm diagnosis of the cause of the aneurysmal vasculopathy. In the absence of a clear aetiology we suggest looking for varicella zoster virus (VZV) replication in the cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) and treating with intravenous acyclovir, aiming for HIV control with appropriate antiretroviral therapy and providing suitable antiplatelet agents. If there is a high index of suspicion of VZV, therapy with acyclovir may be prudent even if the CSF PCR is negative (as may occur after the first 2 weeks of reactivation of infection). Determination of a VZV plasma:CSF IgG ratio is not readily available and would only provide surrogate support for a previous VZV infection in the central nervous system compartment.