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

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.

This study aims to identify inflammatory, viral, renal, and retinal vascular factors independently associated with CSVD in virologically controlled PWH.

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.

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.

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.