Predictors of cerebral small-vessel disease in middle-aged, virologically-controlled people living with HIV

Authors: Antoine Moulignier, Cédric Lamirel, Arbnor Zenuni, Patricia Koskas, Corinne Amiel, Roland Tubiana, Christine Katlama, Soraya Fellahi, Jean-Philippe Bastard, Jacqueline Capeau, Dominique Costagliola, Amélie Yavchitz, Augustin Lecler, Lambert Assoumou, for the Microvascular Brain Retina And Kidney (MicroBREAK) Study Group

Open Forum Infectious Diseases, ofag382,
https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofag382/8721344
Published: 29 June 2026

Abstract

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

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.

Result

Hypertension was the strongest independent correlate of CSVD (OR 4.92, 95% CI 1.23–19.62; p=0.02). 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=0.003) and elevated D-dimer levels (OR 1.52; 1.09–2.12; p=0.01). Increased intraocular pressure was independently related to CSVD (OR 6.37; 1.38–29.4; p=0.02). In contrast, HIV-specific parameters showed no independent relationship with CSVD.

Conclusion

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.

Author notes

The MicroBREAK Study Group members are listed in the Acknowledgment section.

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Supplementary data

ofag382_supplementary_data.docx - docx file