The Role of Atherosclerosis in HIV-Related Stroke in South Africa

Abstract

Stroke in people living with HIV (PLWH) is an incompletely understood entity. The purpose of this cross-sectional research was to study a population of PLWH who have suffered a stroke in a low-and-middle-income country at the epicentre of the world’s HIV epidemic. Of particular interest was exploring the role of atherosclerosis, which appears to be the primary mechanism mediating HIV-related stroke in data from high-income countries. This study was conducted at a quaternary-level hospital in Johannesburg, South Africa, between August 2014 and November 2017. Patients with new-onset stroke were recruited and assessed using investigations including CT angiography and echocardiography. Validated non- invasive biomarkers of subclinical atherosclerosis, namely carotid intima-media thickness and aortic pulse wave velocity, were used to assess the role of atherosclerosis in patients with strokes of different aetiologies. A total of 346 patients were recruited, of which 87 (25.1%) were PLWH. Of these, 33 (37.9%) were newly diagnosed with HIV on presentation with stroke. In the PLWH with ischaemic stroke (n=85, mean age 43.4±12.5 years), vasculopathy was the most common stroke aetiology (28/85, 32.9%), of which only four were due to atherosclerosis (4.7%). There was no evidence of subclinical atherosclerosis in the other 24 PLWH with vasculopathy nor in those with undetermined stroke aetiology. HIV status had no impact on carotid intima-media thickness in multivariate regression models. Vasculopathy was due to varicella-zoster virus in 8/28 PLWH with vasculopathy (21.4%). This was despite excluding patients with abnormal basic cerebrospinal fluid examination and the unavailability of optimal varicella-zoster diagnostics, suggesting the likely under-diagnosis of this potentially treatable stroke risk factor. Routine testing for varicella-zoster in the cerebrospinal fluid of all PLWH with stroke is thus recommended. In the first 6 months of starting antiretroviral therapy, 32.1% of patients had a stroke, translating to a 3.5 times greater stroke risk in this period compared to beyond 6 months (p=0.0002). This was despite excluding all patients with opportunistic infections, suggesting a novel role of the Immune Reconstitution Inflammatory Syndrome as a stroke risk factor in the absence of such infections. This was also shown to be independent of atherosclerosis. xi Cardioembolism accounted for 20% of strokes, compared to 4-9% in previous regional literature. This likely indicates the under-diagnosis of such conventional stroke aetiologies due to resource limitations. Cardiomyopathy was the predominant aetiology of cardioembolic stroke (76.4%), emphasising the need for a cost-effective and accessible biomarker in a region with limited access to echocardiography. In conclusion, our findings of a low atherosclerotic burden, covert varicella-zoster-related strokes, and the role of immune reconstitution in the absence of opportunistic infections are examples of an alternative view to that in the current literature from high-income countries. This may be more applicable to the management of the vast majority of PLWH globally, who mostly reside in low-and-middle-income countri