@article{f4702efe9771426b8b2db31acd026244,
title = "Long-term trends of alanine aminotransferase levels among persons living with human immunodeficiency virus/hepatitis B virus with and without hepatitis delta coinfection",
abstract = "Background: Hepatitis delta virus (HDV) infection accelerates the progression of liver disease in persons living with HIV and hepatitis B virus (HBV) coinfection. We explored the association between HDV infection and alanine aminotransferase (ALT) elevation during tenofovir-containing antiretroviral treatment among persons living with HIV/HBV. Materials and methods: We included persons living with HIV/HBV with and without HDV starting tenofovir-containing antiretroviral therapy (ART) in three European cohorts with at least 18 months of follow-up. We defined HDV infection as a positive anti-HDV antibody test. We assessed risk factors for ALT elevation ≥ 1.25x upper limit of normal after 5 years of tenofovir-treatment using multivariate logistic regression models. The difference in ALT trends between individuals with and without HDV was evaluated using linear mixed effects models. Results: 61/518 (11.8%) participants had an HDV infection. Among individuals with HDV, 63.9% had ALT elevation after 2 years and 55.6% after 5 years of tenofovir, whereas the estimates were 34.1% after two and 27.0% after 5 years in those without HDV. HDV coinfection (adjusted odds ratio 2.8, 95% confidence interval 1.4–5.8) and obesity at baseline (adjusted odds ratio 3.2, 95% confidence interval 1.2–8.0) were associated with ALT elevation after 5 years of tenofovir therapy. Mean ALT levels were consistently higher during follow-up in participants with HDV compared to those without HDV. Conclusion: Persistent ALT elevation is common in persons living with HIV/HBV in Europe despite adequate HBV therapy. HDV coinfection and obesity are independent risk factors for persistent ALT elevation during long-term tenofovir treatment.",
keywords = "HIV, alanine aminotransferase elevation, coinfection, hepatitis B virus, hepatitis D (delta) virus, tenofovir",
author = "Lorin Begr{\'e} and Charles B{\'e}guelin and Anders Boyd and Lars Peters and Rockstroh, {J. rgen} and G{\"u}nthard, {Huldrych F.} and Enos Bernasconi and Matthias Cavassini and Karine Lacombe and Euro-B and Amanda Mocroft and Gilles Wandeler and Andri Rauch",
note = "Funding Information: This study received funding through an investigator-initiated trial grant from Gilead Sciences (CO-SW-985-5602), from the NEAT-ID Foundation, the Department of Teaching and Research, Inselspital, Bern University Hospital, and the Liquid Biobank Bern. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. This study has been financed within the framework of the Swiss HIV Cohort Study, supported by the Swiss National Science Foundation (grant #201369), by SHCS project #809 and by the SHCS research foundation. EuroSIDA has received funding from ViiV Healthcare LLC, Janssen Scientific Affairs, Janssen R&D, Bristol-Myers Squibb Company, Merck Sharp and Dohme Corp., Gilead Sciences and the European Union{\textquoteright}s Seventh Framework Program for research, technological development and demonstration under EuroCoord grant agreement no 260694. The participation of centers from Switzerland has been supported by The Swiss National Science Foundation (Grant 148522). The study is also supported by a grant (grant number DNRF126) from the Danish National Research Foundation and by the International Cohort Consortium of Infectious Disease (RESPOND). LB{\textquoteright}s work was supported by the «Young Talents in Clinical Research» program of the Swiss Academy of Medical Sciences and G. and J. Bangerter-Rhyner Foundation (Grant YTCR 13/19). GW was supported by a Professorship from the Swiss National Science Foundation (PP00P3_176944). Funding Information: AR reports support to his institution for advisory boards and/or travel grants from MSD, Gilead Sciences, Pfizer and Abbvie, and an investigator initiated trial (IIT) grant from Gilead Sciences. All remuneration went to his home institution and not to AR personally, and all remuneration was provided outside the submitted work. GW received financial support for advisory boards, lectures and/or travel from MSD, Gilead Sciences, and ViiV, and investigator initiated study grants from Gilead Sciences and Roche Diagnostics, all paid to his home institution and provided outside the submitted work. HG has received unrestricted research grants from Gilead, NIH, Yvonne Jacob Foundation, and the Swiss National Science Foundation. He has been advisor/consultant or DSMB member to Merck, Gilead, ViiV, GSK, Johnson and Johnson, and Novartis and has received honoraria. AM received honoraria, travel support, lecture fees and consultancy payments from Gilead, ViiV and Eiland, and Bonnin, outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher Copyright: Copyright {\textcopyright} 2022 Begr{\'e}, B{\'e}guelin, Boyd, Peters, Rockstroh, G{\"u}nthard, Bernasconi, Cavassini, Lacombe, Mocroft, Wandeler and Rauch.",
year = "2022",
month = sep,
day = "15",
doi = "https://doi.org/10.3389/fmed.2022.988356",
language = "English",
volume = "9",
journal = "Frontiers in Medicine",
issn = "2296-858X",
publisher = "Frontiers Media",
}