Predictors of Ischemic and Hemorrhagic Strokes Among People Living With HIV: The D:A:D International Prospective Multicohort Study.

Background: Hypertension is a stronger predictor of hemorrhagic than ischemic strokes in the general population. We aimed to identify whether hypertension or other risk factors, including HIV-related factors, differ in their associations with stroke subtypes in people living with HIV (PLWHIV).
Methods: HIV-1-positive individuals from the Data collection on Adverse events of anti-HIV Drugs (D:A:D) study were followed from the time of first blood pressure (BP) measurement after 1/1/1999 or study entry until the first of a validated stroke, 6 months after last follow-up or 1/2/2014. Stroke events were centrally validated using standardized criteria. Hypertension was defined as one systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg. Poisson and Cox proportional hazards regression models determined associations of established cerebro/cardiovascular disease and HIV-related risk factors with stroke and tested whether these differed by stroke subtype.
Findings: 590 strokes (83 hemorrhagic, 296 ischemic, 211 unknown) occurred over 339,979 person-years (PYRS) (incidence rate/1000 PYRS 1.74 [95% confidence interval (CI) 1.60-1.88]). Common predictors of both hemorrhagic and ischemic strokes were hypertension (relative hazard 3.55 [95% CI 2.29-5.50] and 2.24 [1.77-2.84] respectively) and older age (1.28 [1.17-1.39] and 1.19 [1.12-1.25]). Male gender (1.62 [1.14-2.31] and 0.60 [0.35-0.91]), previous cardiovascular events (4.03 [2.91-5.57] and 1.44 [0.66-3.16]) and smoking (1.90 [1.41-2.56] and 1.08 [0.68-1.71]) were stronger predictors of ischemic then hemorrhagic strokes, whereas hypertension, hepatitis C (1.32 [0.72-2.40] and 0.46 [0.30-0.70]) and estimated glomerular filtration rate < 60 mL/min/1.72 m ³ (4.80 [2.47-9.36] and 1.04 [0.67-1.60]) were stronger predictors of hemorrhagic than ischemic strokes. A CD4 count < 200 cells/μL was associated with an increased risk of hemorrhagic stroke only.
Interpretation: Risk factors for stroke may differ by subtype in PLWHIV, emphasizing the importance of further research to increase the precision of stroke risk estimation.
Competing Interests: PR has served as a scientific adviser to Bristol-Myers Squibb, Gilead Sciences, Grupo Ferrer Internacional, GlaxoSmithKline, Janssen Pharmaceutica, Merck, and ViiV Healthcare; has served on data and safety monitoring boards and endpoint adjudication committees for Janssen Pharmaceutica; reports honoraria to his institution for speaking engagements at scientific conferences from Bristol-Myers Squibb, Gilead Sciences, and GlaxoSmithKline; and reports research support from Gilead Sciences, ViiV Healthcare, Merck, Janssen Pharmaceutica, Bristol-Myers Squibb, Abbott Laboratories, and Boehringer Ingelheim. ML reports grants from Boehringer Ingelheim, Gilead Sciences, Merck Sharp & Dohme, Bristol-Myers Squibb, Janssen-Cilag, and ViiV HealthCare and personal fees from Gilead Sciences and Sirtex Pty Ltd, outside the submitted work. CS reports grants from The D:A:D Oversight Committee, during the conduct of the study, personal fees from Gilead Sciences, personal fees from ViiV Healthcare, and personal fees from Janssen-Cilag, outside the submitted work. FB reports personal fees and non-financial support from ViiV Healthcare, Gilead, BMS, Janssen, and MSD and grants from Gilead and Janssen, outside the submitted work; CP reports personal fees from Gilead, outside the submitted work; AM reports personal fees from ViiV and Gilead, outside the submitted work. HK has received travel grants from Gilead and her institution received consultancy fees from Gilead and MSD; OK reports personal fees from Gilead, personal fees from MSD, personal fees from ViiV, non-financial support from Gilead, personal fees from Gilead, personal fees from Janssen, non-financial support from ViiV, and non-financial support from BMS, outside the submitted work; SDW. CIH, LR, DK, AP, WE-S, ADM, SDW and JDL have no disclosures to declare.