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Brief Report

Hyperbilirubinemia Is Associated With a Decreased Risk of Carotid Atherosclerosis in HIV-Infected Patients on Virological Suppression

Muccini, Camilla, MD*; Galli, Laura, MSc; Poli, Andrea, MSc; Carbone, Alessia, MD; Maillard, Myriam, MD; Giusti, Maria Cristina, MD; Spagnuolo, Vincenzo, MD*; Bigoloni, Alba, SN; Guffanti, Monica, MD; Gianotti, Nicola, MD; Lazzarin, Adriano, MD; Castagna, Antonella, MD*,†

JAIDS Journal of Acquired Immune Deficiency Syndromes: December 15, 2018 - Volume 79 - Issue 5 - p 617–623
doi: 10.1097/QAI.0000000000001854
Clinical Science

Objective: To investigate the association between total, direct, and indirect bilirubin and the presence of carotid lesions in a large sample of HIV-1–infected patients on virological suppression.

Design: Retrospective study on adult HIV-1–infected patients, with a carotid ultrasound (CUS) examination performed between January 2008 and August 2016, with HIV-RNA <50 copies per milliliter at CUS and without previous cardiovascular events.

Methods: Intima media thickness was measured in 4 segments: carotid common artery and bifurcation on the left and right sides. Carotid lesion was defined as an intima media thickness ≥1.5 mm in ≥1 region at CUS. Patients were classified as: normal if all bilirubin values before CUS were below the upper normal limit and with hyperbilirubinemia if ≥1 bilirubin value above upper normal limit before CUS was recorded. Multivariate logistic regression was used to determine whether hyperbilirubinemia showed association with the presence of ≥1 carotid lesion, after adjusting for confounding factors.

Results: Overall, 903 patients were evaluated, 511 with ≥1 and 392 without carotid lesions. At multivariate analysis, total [adjusted odds ratio (95% confidence interval) 0.57 (0.36 to 0.90), P = 0.016] and indirect hyperbilirubinemia before CUS [adjusted odds ratio (95% confidence interval) 0.62 (0.40 to 0.97), P = 0.036] were associated with a lower risk of carotid lesions in addition to younger age, negative hepatitis C virus antibodies, higher nadir CD4+, lower low-density lipoprotein cholesterol, higher high-density lipoprotein cholesterol, lower triglycerides, and no use of statin; no effect of atazanavir treatment on carotid lesions was detected.

Conclusions: In HIV-1–treated patients, total or indirect hyperbilirubinemia was likely associated with the absence of carotid lesions.

*Vita-Salute San Raffaele University, Milan, Italy;

Infectious Diseases, IRCCS San Raffaele, Milan, Italy; and

Department of Clinical Neuroscience, IRCCS San Raffaele, Milan, Italy.

Correspondence to: Camilla Muccini, Vita-Salute San Raffaele University, via Stamira D'Ancona 20 Milano 20127, Italy (e-mail:

The IDD-HSR cohort (Infectious Diseases Database of the San Raffaele Hospital) was supported by internal and external funding by Gilead, ViiV Health Care, Merck Sharp & Dohme, and Janssen-Cilag. The funding source had no role in the design of the study, analyses, interpretation of the data, or decision to submit results.

Presented in part at the 16th European AIDS Conference; October 25–27, 2017; Milan, Italy; Abstract A-919-0014-00629.

A. Castagna has received consultancy payments and speaking fee from Bristol-Myers Squibb, Gilead, ViiV Health Care, Merck Sharp & Dohme, Janssen-Cilag, and Vincenzo Spagnuolo from Gilead, ViiV Health Care, and Janssen-Cilag. N.G. has been advisor for Gilead Sciences, AbbVie, and Janssen-Cilag and has received speakers' honoraria from Gilead Sciences, ViiV, Bristol-Myers Squibb, Merck Sharp and Dohme, Roche, AbbVie, Boehringer Ingelheim, and Janssen-Cilag. A.L. has received consultancy payments and speaking fee from Bristol-Myers Squibb, Gilead, ViiV Health Care, Merck Sharp & Dohme, Janssen-Cilag, and Abbvie. The remaining authors have no conflicts of interest to disclose.

C.M. helped to design the study, participated in the analysis of the data, and wrote the manuscript; L.G. analyzed the data and wrote the manuscript; A.P. collected clinical and laboratory data; A. Carbone conceived the study and collected carotid ultrasound data; M.C.G. performed carotid ultrasound examinations; M.M., V.S., A.B., M.G., and N.G., contributed to the interpretation of the results and to writing the manuscript; A.L. and A. Castagna conceived the study, participated in the analysis of the data, and wrote the initial draft of the manuscript; and all authors have seen and approved the final version.

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Received March 07, 2018

Accepted August 06, 2018

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