Characterization and stratification of risk factors of stroke in people living with HIV : a theory-informed systematic review

Abstract

BACKGROUND : Identification and stratification of risk factors for stroke among individuals living with HIV (PLWH) will facilitate primary prevention and prognostication, as well as strategies aimed at optimizing neurorehabilitation. This review sought to characterize and stratify the risk factors associated with stroke in PLWH. METHODS : The review was structured in accordance with the preferred items for reporting systematic reviews and meta-analysis (PRISMA) checklist. The epidemiological triangle, Bradford criteria, and Rothman causality model further informed the review. The review outcomes encompassed cardiovascular factors, HIV-related factors, and personal and extrinsic factors associated with stroke in PLWH. We conducted searches in PubMed, Scopus, Medline, Web of Science, Cumulative Index for Nursing and Allied Health Literature, and African Journal (SABINET). Data screening and extraction were independently performed utilizing predefined eligibility criteria and a data-extraction template. Narrative synthesis and risk stratification were employed to analyze the results. RESULTS : Thirty studies (22 cohorts and eight case–control) with a sample size of 353,995 participants were included in this review. The mean age of the participants was 45.1 ± 10.7 years. The majority of the participants (72.4%) were male. Risk factors for stroke in PLWH include cardiovascular factors (advanced age, tobacco use, hypertension, diabetes, atrial fibrillation, etc.), HIV-related factors (high viral load and low nadir CD4 count), personal factors (advanced age and female sex), and comorbidities (hepatitis C virus infection, chronic kidney disease, coronary artery disease, and liver fibrosis or cirrhosis). Diabetes, atrial fibrillation, smoking habits, hypertension, age, and viral load demonstrated a high likelihood of association with stroke in PLWH and should be prioritized when constructing clinical prediction algorithms for HIV-related stroke. CONCLUSIONS : The most important factors were hypertension and chronic kidney disease, followed by smoking, dyslipidemia, diabetes, HCV, HBV, CD4 count, use of ART, TB, and substance use (cocaine). The least important factors were age, sex, ethnicity, obesity, alcohol use, ART duration, and viral load. The predictive significance of these factors is still evolving, given the average moderate certainty of evidence. Predictive and preventative models should target factors with a high causality index and low investigative costs. TRIAL REGISTRATION : The review is part of a larger review registered with the PROSPERO (ID: CRD42024524494).