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.
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.
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.
No deleterious effect of ART class exposure on the risk of CSVD was found for middle-aged treated PLHIVs.
aINSERM, Sorbonne Université, Institut Pierre-Louis d'Epidémiologie et de Santé Publique (IPLESP), Paris, France;
bFondation Adolphe de Rothschild, Service de Neurologie, Paris, France;
cSorbonne Paris Cité, INSERM, Infection, Antimicrobials, Modelling, Evolution, UMR 1137, APHP, Service de Maladies Infectieuses et Tropicales, Hôpital Bichat–Claude-Bernard, Université Paris-Diderot, Paris, France;
dService de Radiologie, Fondation Adolphe de Rothschild, Paris, France;
eService d'Ophtalmologie, Fondation Adolphe de Rothschild, Paris, France;
fAPHP, Hôpital Saint-Antoine, Service de Maladies Infectieuses et Tropicales, Paris, France;
gAPHP, Hôpital Pitié–Salpêtrière, Service de Maladies Infectieuses et Tropicales, Paris, France;
hAPHP, Hôpital Tenon, Service de Maladies Infectieuses et Tropicales, Paris, France; and
iFondation Adolphe de Rothschild, Unité de Recherche Clinique, Paris, France.
Correspondence to: Antoine Moulignier, MD, Service de Neurologie, Fondation Adolphe de Rothschild, 29 rue Manin, 75019 Paris, France (e-mail: email@example.com).
Supported by the Agence Nationale de Recherche sur le SIDA et les Hépatites Virales.
A.M. reports consultancy fees and/or nonfinancial support from Biogen Idec, Novartis, Gilead, MSD, Teva, and Merck-Serono, outside the submitted work. J.S. reports consultancy fees from Bayer Pharmaceuticals, Medtronic, Philips Healthcare, Gilead, Novartis, Sanofi, and IRIS (Institut de Recherche Servier) and nonfinancial support from GE Healthcare and Bayer Pharmaceuticals, outside the submitted work. F.-X.L. reports consultancy fees from MSD and Gilead, outside the submitted work. C.L. reports consultancy fees and/or nonfinancial support from Allergan, Thea, and Alcon, outside the submitted work. P.R. reports nonfinancial support from General Electrics, outside the submitted work. C.K. reports grants and/or consultancy fees from Merck-Sharp-Dome, Bristol-Myers-Squibb, ViiV Healthcare, Gilead Sciences, and Janssen Pharmaceuticals, outside the submitted work. Y.Y. reports consultancy fees from Abbvie, BMS, Gilead, MSD, Roche, Johnson & Johnson, ViiV Healthcare, and Pfizer, from Janssen for board membership and payment for development of educational presentations, outside the submitted work. G.P. reports grants or consultancy fees from Gilead, Abbvie, BMS, ViiV, GSK, Janssen, and Nephrotek, outside the submitted work. P.-M.G. reports grants and/or consultancy fees from BMS, Janssen, Gilead, ViiV Healthcare, and Abbvie, outside the submitted work. D.C. reports grants from Janssen-Cilag (2017–2018), Merck-Sharp & Dohme-Chibret (2015–2017), and ViiV (2015), personal fees from Janssen-Cilag (2016, 2018), Merck-Sharp & Dohme-Chibret (2015, 2017) for lectures, personal fees from ViiV (2015) for travel/accommodations/meeting expenses, personal fees from Gilead France from 2011 until December 2015 for French HIV board, personal fees from Innavirvax (2015 and 2016), and Merck Switzerland (2017) for consultancy all outside the submitted work. The remaining authors have no conflicts of interest to disclose.
O.G., A.M., C.L., D.C., and L.A. designed the study; E.J., J.S., F.-X.L., N.V., R.T., A.C., P.R., J.-C.S., C.K., Y.Y., G.P., and P.-M.G. collected data; E.J., L.A., O.G., and D.C. conducted the statistical analysis; E.J., O.G., A.M., C.L., D.C., and L.A. drafted the report; and A.M., L.S., and D.C. coordinated the study. All authors provided input and approved the final version of the manuscript. A.M. and D.C. have full access to all the data in the study and had final responsibility to decide to submit for publication.
The MicroBREAK Study Group members are listed in the Acknowledgment section.
Received October 26, 2018
Accepted March 18, 2019