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Purpose: To compare peripapillary retinal nerve-fiber-layer (pRNFL) thickness, total retina macular volume, and ganglion-cell-layer (GCL) macular volume and thickness between persons living with HIV (PLHIVs) with well-controlled infections and good immune recovery, and sex- and age-matched HIV-uninfected controls (HUCs)., Methods: This prospective cross-sectional study (www.clinicaltrials.gov identifier: NCT02003989) included 56 PLHIVs, infected for ≥10 [median 20.2] years and with sustained plasma HIV-load suppression on combined antiretroviral therapy (cART) for ≥5 years, and 56 matched HUCs. Participants underwent spectral-domain optical coherence tomography (SD-OCT) with thorough ophthalmological examinations and brain magnetic resonance imaging (MRI). Their overall and quadrant pRNFL thicknesses, total macular volumes, and GCL macular volumes and thicknesses were compared. Cerebral small-vessel diseases (CSVD) complied with STRIVE criteria., Results: Median [interquartile range, IQR] ages of PLHIVs and HUCs, respectively, were 52 [46-60] and 52 [44-60] years. Median [IQR] PLHIVs' nadir CD4+ T-cell count and current CD4/CD8 T-cell ratio were 249/μL [158-350] and 0.95 [0.67-1.10], respectively; HIV-seropositivity duration was 20.2 [15.9-24.5] years; cART duration was 16.8 [12.6-18.6] years; and aviremia duration was 11.4 [7.8-13.6] years. No significant between-group pRNFL thickness, total macular volume, macular GCL-volume and -thickness differences were found. MRI-detected CSVD in 21 (38%) PLHIVs and 14 (25%) HUCs was associated with overall thinner pRNFLs, and smaller total retina and GCL macular volumes, independently of HIV status., Conclusions: SD-OCT could not detect pRNFL thinning or macular GCL-volume reduction in well-sustained, aviremic, cART-treated PLHIVs who achieved good immune recovery. However, CSVD was associated with thinner pRNFLs and GCLs, independently of HIV status., Competing Interests: C. Lamirel, N. Valin, J. Savatosky, A.-S. Alonso, J.-P. Vincensini, L. Salomon and I. Cochereau have no disclosures to report. F.-X. Lescure has received funding for board membership from Gilead Sciences and MSD France; for lectures from BioMérieux, Gilead Sciences and MSD France; and to travel to meetings from Gilead Sciences, MSD France, Astellas and Eumedica. P. Girard has received support to travel to meetings and accommodations from Bayer and Leo Pharma. P.-M. Girard has received honoraria for participation on international advisory boards from Gilead, ViiV Healthcare and Abbvie, and honoraria for speaking engagements from Janssen and BMS. A. Moulignier has received research support from the Association Nationale de Recherche sur le SIDA (ANRS); funding for lectures from Biogen Idec and Norvartis, and to travel to meetings from Biogen Idec and Teva Pharma. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Cerebral small-vessel disease (CSVD) is a chronic disease accounting for one-third of strokes and the second etiology of dementia. Despite sustained immunovirological control, CSVD prevalence is doubled in middle-aged persons living with HIV (PLHIVs), even after adjustment for traditional cardiovascular risk factors. We aimed to investigate whether exposure to any antiretroviral drug class could be associated with an increasing risk of CSVD., Methods: The MicroBREAK-2 case-control study (NCT02210130) enrolled PLHIVs aged 50 years and older, treated with combined antiretroviral therapy for ≥5 years, with plasma HIV load controlled for ≥12 months. Cases were PLHIVs with radiologically defined CSVD, and controls were CSVD-free PLHIVs matched for age (±5 years), sex, and year of HIV diagnosis (±5 years). Multivariable conditional logistic regression analyses focused on cumulative exposure to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and/or exposure to integrase inhibitors (yes or no), adjusted for hypertension, CD4 nadir, current CD4/CD8 ratio, and HIV transmission group., Results: Between May 2014 and April 2017, 77 cases and 77 controls (85.7% males) were recruited. PLHIVs' median age was 57.6 years, and median HIV diagnosis year was 1992. The increasing risk of CSVD was not associated with exposure to any ART class., Conclusion: No deleterious effect of ART class exposure on the risk of CSVD was found for middle-aged treated PLHIVs.

Background: Silent cerebral small-vessel disease (CSVD) is defined as white matter hyperintensities, silent brain infarction, or microbleeds. CSVD is responsible for future vascular events, cognitive impairment, frailty, and shorter survival. CSVD prevalence among middle-aged people living with well-controlled human immunodeficiency virus (HIV) infection (PLHIV) is unknown., Methods: The French National Agency for Research on AIDS and Viral Hepatitis (ANRS) EP51 Microvascular Brain Retina and Kidney Study (MicroBREAK; NCT02082574) is a cross-sectional study with prospective enrollment of treated PLHIV, ≥50 years old with viral load controlled for ≥12 months, and frequency age- and sex-matched HIV-uninfected controls (HUCs). It was designed to estimate CSVD prevalence on 3T magnetic resonance imaging (3D fluid-attenuated inversion recovery, transversal T2-weighted gradient-echo imaging and diffusion-weighted imaging), as diagnosed by 2 blinded neuroradiologists. A logistic regression model was used to assess the impact of HIV on CSVD after adjustment for traditional risk factors., Results: Between June 2013 and May 2016, 456 PLHIV and 154 HUCs were recruited. Median age was 56 and 58 years, respectively (P = .001), among whom 84.9% and 77.3%, respectively (P = .030), were men. CSVD was detected in 51.5% of PLHIV and 36.4% of HUCs with an adjusted odds ratio (aOR) of 2.3. The HIV impact differed according to age, with aOR values of 5.3, 3.7, and 1.0 for age groups <54, 54-60, and >60 years, respectively (P = .022). Older age, hypertension, and lower CD4 cell count nadir were independently associated with a higher risk of CSVD among PLHIV., Conclusions: HIV is an independent risk factor for CSVD. Despite sustained immunovirological control, the CSVD prevalence was twice as high among middle-aged PLHIV than HUCs., Clinical Trials Registration: NCT02082574.