Stroke and HIV: Emerging mechanisms and management in a changing epidemic

BACKGROUND: Stroke is increasingly recognized as an important cause of morbidity and mortality in people living with HIV (PLWH). Although advances in antiretroviral therapy (ART) have transformed HIV into a chronic condition, cerebrovascular complications remain common and often underrecognized. AIMS: This review summarized current understanding of the pathogenesis, clinical features, investigations, and management of stroke in PLWH, highlighting knowledge gaps and priorities for future research. SUMMARY OF EVIDENCE: HIV-associated stroke is multifactorial. Mechanisms include HIV-associated vasculopathy, opportunistic infections, immune reconstitution inflammatory syndrome (IRIS), and traditional vascular risk factors accelerated by HIV and ART. Clinical presentations may resemble those in HIV-negative individuals but occur at a younger age, with distinct subtype distributions and a higher frequency of concomitant infection. Investigation requires a tiered approach: standard stroke imaging and cardiac work-up, supplemented by cerebrospinal fluid analysis and advanced vessel wall imaging in patients with suspected inflammatory or infectious etiology. Reperfusion therapies appear feasible in stable HIV disease, but evidence remains limited. Outcomes are shaped by immune status, access to care, and comorbidities, with higher recurrence and cognitive decline reported in several cohorts. Real-world challenges include stigma, clinician awareness gaps, and inequities in diagnostics and treatment, particularly in low-resource settings. CONCLUSIONS: Stroke in PLWH is an emerging global health challenge. Clinicians should maintain a high index of suspicion in younger patients and those with advanced disease or recent ART initiation. Multidisciplinary care pathways and equitable access to diagnostics and secondary prevention are essential. Future research must address unresolved questions around vasculopathy, IRIS, small vessel disease, and long-term cognitive outcomes to guide evidence-based management.