Association of HIV and Opportunistic Infections With Incident Stroke: A Nationwide Population-Based Cohort Study in Taiwan

Abstract

Background HIV-associated vasculopathy and opportunistic infections (OIs) might cause vascular atherosclerosis and aneurysmal arteriopathy, which could increase the risk of incident stroke. However, few longitudinal studies have investigated the link between HIV and incident stroke. This cohort study evaluated the association of HIV and OIs with incident stroke. Methods We identified adults with HIV infection in 2000–2012, using the Taiwan National Health Insurance Research Database. A control cohort without HIV infection, matched for age and sex, was selected for comparison. Stroke incidence until December 31, 2012 was then ascertained for all patients. A time-dependent Cox regression model was used to determine the association between OIs and incident stroke among HIV patients. Results Among a total of 106,875 patients (21,375 HIV patients and 85,500 matched controls), stroke occurred in 927 patients (0.87%) during a mean follow-up period of 5.44 years, including 672 (0.63%) ischemic strokes and 255 (0.24%) hemorrhagic strokes. After adjusting for other covariates, HIV infection was an independent risk factor for incident all-cause stroke [adjusted hazard ratio (AHR) 1.83; 95% confidence interval (CI) 1.58–2.13]. When type of stroke was considered, HIV infection increased the risks of ischemic (AHR 1.33; 95%CI 1.09–1.63) and hemorrhagic stroke (AHR 2.01; 95%CI 1.51–2.69). The risk of incident stroke was significantly higher in HIV patients with cryptococcal meningitis (AHR 4.40; 95%CI 1.38–14.02), cytomegalovirus disease (AHR 2.79; 95%CI 1.37–5.67), and Penicillium marneffei infection (AHR 2.90; 95%CI 1.16–7.28). Conclusions HIV patients had an increased risk of stroke, particularly those with cryptococcal meningitis, cytomegalovirus, or P. marneffei infection.

HIV Infection and Risk of Cardiovascular Diseases Beyond Coronary Artery Disease

“…It is estimated that 1–5% of PLWH experience clinical stroke, although ischemic lesions are seen in 4–34% of brain autopsies in this population [52]. Studies have reported increased risks of all-cause stroke (adjusted HR of 1.6–1.8) [53, 54], ischemic stroke (adjusted HR of 1.2–1.4) [53, 55, 56], and hemorrhagic stroke (adjusted HR of 2–3.3) in PLWH compared to uninfected individuals [53, 57]. Risk factors associated with these increased risks vary in different studies, but a lower CD4 count before initiation of ART [54], exposure to abacavir [54], higher HIV RNA levels [55], having AIDS-defining conditions [57], African American ethnicity [58], hepatitis C infection [57], illicit drug or alcohol abuse [57], heavy alcohol consumption [59], intracranial lesions [57], and coagulopathy [57] were all strongly associated with a higher risk of stroke.…”

“…With the introduction of ART, ischemic stroke has become the more common subtype of stroke identified in PLWH [52, 53, 64]. Some mechanisms that are thought to contribute to the higher prevalence of ischemic stroke in PLWH include: HIV-associated vasculopathy (20–32% prevalence) [60, 61], coagulopathy (19–49%) [60, 61, 65], opportunistic infection (13–28%) [61, 65], and cardioembolism (5–15%) [61, 65].…”

The association between human herpesvirus infections and stroke: a systematic review protocol

“… 9–12 The effects of other members of the herpesvirus family on vascular events are less clear, although cytomegalovirus (CMV) is hypothesised to modulate stroke risk, especially among immunocompromised populations. 13 …”

p17 from HIV induces brain endothelial cell angiogenesis through EGFR-1-mediated cell signalling activation

“…Recently, Montoya et al (2017) 19 , showed increased expression of vascular endothelial cell growth factor, angiopoietin-2 and Tie-2 associated with arterial fibrosis, arterial stiffening and altered pulse pressure in patients with neurocognitive disturbance and HIV. Similarly, Yen et al (2017) 20 showed a strong correlation between glomerular filtration rate and neurocognitive decline in HIV positive individuals leading to a body of thinking around a direct relationship between vascular cognitive impairment associated to HIV disorder 21 . We previously showed that p17 from HIV caused dementia-like symptoms in a murine model following hippocampal injection 5 .…”