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BRIEF RESEARCH REPORT article

Front. Pharmacol.
Sec. Pharmacology of Infectious Diseases
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1341612

Low plasma levels of BTLA and LAG-3 before HCV therapy are associated with metabolic disorders after HCV eradication in persons with HIV/HCV coinfection: a retrospective study

Provisionally accepted
Rubén Martín-Escolano Rubén Martín-Escolano 1Ana Virseda-Berdices Ana Virseda-Berdices 1Juan Berenguer Juan Berenguer 2Juan González-García Juan González-García 3Óscar Brochado-Kith Óscar Brochado-Kith 1Amanda Fernández-Rodríguez Amanda Fernández-Rodríguez 1Cristina Díez Cristina Díez 2Victor Hontañon Victor Hontañon 3Salvador Resino Salvador Resino 1*María Angeles Jiménez-Sousa María Angeles Jiménez-Sousa 1*
  • 1 Carlos III Health Institute (ISCIII), Madrid, Madrid, Spain
  • 2 Gregorio Marañón Hospital, Madrid, Madrid, Spain
  • 3 University Hospital La Paz, La Paz, Madrid, Spain

The final, formatted version of the article will be published soon.

    Background: Understanding the predictors of metabolic disorders in persons with HIV/HCV coinfection post-HCV therapy is crucial for improving patient outcomes. Since immune checkpoint proteins are usually upregulated in these persons with HIV/HCV coinfection, we aimed to evaluate the association between plasma immune checkpoint proteins at baseline (before HCV therapy) and metabolic disturbances during the follow-up (about five years after successful HCV treatment) in persons with HIV/HCV coinfection.We performed a retrospective study on 80 persons with HIV/HCV coinfection with advanced fibrosis or cirrhosis who cleared HCV infection after successful HCV therapy and were followed for about 5 years after completion of HCV treatment. Plasma samples were collected at baseline. Immune checkpoint proteins were analyzed using a Luminex 200 TM analyzer. Outcomes were the development of a metabolic event (type 2 diabetes mellitus and/or dyslipidemia) and the change in Triglycerides and glucose (TyG) index.Results: During follow-up, 21 (26%) patients developed metabolic events (type 2 diabetes mellitus/ dyslipidemia), and 29 (46.0%) patients had an increase in TyG during the follow-up.Low baseline values of BTLA and LAG-3, two immune checkpoint proteins, were associated with the development of metabolic events (aAMR= 0.69 and aAMR= 0.71, respectively) and with increases in TyG values (aAMR= 0.72 and aAMR= 0.70, respectively). In addition, other immune checkpoint proteins were also inversely associated with increases in TyG.We discovered that low plasma levels of BTLA and LAG-3 before HCV therapy significantly correlate with an increased risk of developing metabolic disorders after treatment.

    Keywords: HIV/HCV-coinfection, HCV therapy, Immune checkpoint proteins, type 2 diabetes mellitus, Dyslipidemia, TyG index

    Received: 20 Nov 2023; Accepted: 04 Oct 2024.

    Copyright: © 2024 Martín-Escolano, Virseda-Berdices, Berenguer, González-García, Brochado-Kith, Fernández-Rodríguez, Díez, Hontañon, Resino and Jiménez-Sousa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Salvador Resino, Carlos III Health Institute (ISCIII), Madrid, 28220, Madrid, Spain
    María Angeles Jiménez-Sousa, Carlos III Health Institute (ISCIII), Madrid, 28220, Madrid, Spain

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.