Predictors of Cerebral Small-Vessel Disease in Middle-Aged, Virologically Controlled People Living With HIV.

BACKGROUND: Despite durable viral suppression with antiretroviral therapy (ART), non-AIDS comorbidities remain frequent in aging people with HIV (PWH). Cerebral small-vessel disease (CSVD), a major contributor to stroke and cognitive decline, is up to twice as prevalent in middle-aged ART-treated PWH. Mechanisms underlying this excess risk remain unclear. OBJECTIVE: This study aims to identify inflammatory, viral, renal, and retinal vascular factors independently associated with CSVD in virologically controlled PWH. METHODS: The case-control MicroBREAK-2 study (NCT02210130), nested in the PWH group of the MicroBREAK-1 study, included 80 ART-treated (≥5 years) PWH aged ≥50 years with MRI-defined CSVD and 80 matched CSVD-free controls (age ± 5 years, sex, year of HIV diagnosis ± 5 years). Participants underwent brain MRI, renal, carotid, and orbital color Doppler ultrasonography, and comprehensive ophthalmologic assessment. Circulating inflammatory and coagulation biomarkers, Epstein-Barr virus plasma load, and antiretroviral exposure were measured. Independent associations were identified using conditional logistic regression with LASSO selection and bootstrap resampling. RESULTS: Hypertension was the strongest independent correlate of CSVD (OR 4.92, 95% CI 1.23-19.62; P = .02). Markers of persistent inflammatory and coagulative activity were also independently linked to CSVD, including higher white blood cell count (OR 1.58; 1.17-2.14; P = .003) and elevated D-dimer levels (OR 1.52; 1.09-2.12; P = .01). Increased intraocular pressure was independently related to CSVD (OR 6.37; 1.38-29.4; P = .02). In contrast, HIV-specific parameters showed no independent relationship with CSVD. CONCLUSIONS: In virologically suppressed PWH, CSVD is primarily associated with hypertension and persistent low-grade inflammation rather than HIV-specific factors, underscoring the need for aggressive cardiovascular risk management.