{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T03:17:26Z","timestamp":1774581446292,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Background: Co-infections with HIV, HBV, and HDV pose significant public health challenges, especially in populations exposed parenterally. Romania hosts a unique pediatric HIV cohort of individuals born 1987\u20131995 who acquired HIV iatrogenically. This study assessed the prevalence, hepatic impact, and management of HIV\u2013HBV\u2013HDV co-infection in 130 long-term survivors from Gala\u021bi County. Methods: Patients underwent clinical, laboratory, and FibroScan assessments. HBV and HDV serology and viral loads were measured, and antiretroviral therapy regimens, including tenofovir-based therapies, were reviewed. Entecavir or Bulevirtide was applied when indicated. Results: HBV infection was present in 57.7% of cohort patients versus 20% in non-cohort PLWH, and HDV co-infection in 7.7% of cohort patients. Hepatic fibrosis increased from HBV-uninfected to HBV\/HDV co-infected individuals. HIV impairs viral clearance and exacerbates liver injury via immune dysregulation and chronic inflammation. Despite TDF-based ART, replicative HBV was detected in eight patients, managed with Entecavir. Bulevirtide therapy for HDV was initiated in eligible patients, with minor adverse events. Conclusions: Pediatric HIV cohort survivors show high rates of HBV and HDV co-infection and progressive hepatic fibrosis. Optimized antiviral therapy and adherence support are essential to control viral replication and reduce liver-related complications.<\/jats:p>","DOI":"10.3390\/pathogens14121261","type":"journal-article","created":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T12:20:57Z","timestamp":1765369257000},"page":"1261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Triple Burden of HIV, HBV and HDV in Adults with Childhood Parenterally Acquired Infections: A Romanian Single-Center Study"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4762-0755","authenticated-orcid":false,"given":"Manuela","family":"Arbune","sequence":"first","affiliation":[{"name":"Clinical Medical Department, Medicine and Pharmacy Faculty, \u201cDunarea de Jos\u201d University, 800008 Galati, Romania"},{"name":"Infectious Diseases Clinic Hospital, 800179 Galati, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5901-0818","authenticated-orcid":false,"given":"Alina-Viorica","family":"Iancu","sequence":"additional","affiliation":[{"name":"Infectious Diseases Clinic Hospital, 800179 Galati, Romania"},{"name":"Morphological and Functional Sciences Department, Medicine and Pharmacy Faculty, \u201cDunarea de Jos\u201d University, 800008 Galati, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4237-2297","authenticated-orcid":false,"given":"Monica-Daniela","family":"Padurariu-Covit","sequence":"additional","affiliation":[{"name":"Doctoral School of Biomedical Sciences, \u201cDunarea de Jos\u201d University, 800008 Galati, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2710-7284","authenticated-orcid":false,"given":"Alina","family":"Plesea-Condratovici","sequence":"additional","affiliation":[{"name":"Medical Department, Medicine and Pharmacy Faculty, \u201cDunarea de Jos\u201d University, 800008 Galati, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9500-4498","authenticated-orcid":false,"given":"Anca-Adriana","family":"Arbune","sequence":"additional","affiliation":[{"name":"Neurology Department, Fundeni Clinical Institute, 022328 Bucharest, Romania"},{"name":"Multidisciplinary Integrated Center of Dermatological Interface Research (MIC-DIR), \u201cDun\u0103rea de Jos\u201d University, 800008 Galati, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3111-4089","authenticated-orcid":false,"given":"Catalin","family":"Plesea-Condratovici","sequence":"additional","affiliation":[{"name":"Morphological and Functional Sciences Department, Medicine and Pharmacy Faculty, \u201cDunarea de Jos\u201d University, 800008 Galati, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","unstructured":"Joint United Nations Programme on HIV\/AIDS (2025, July 12). Global HIV & AIDS Statistics\u20142023 Fact Sheet. Geneva: UNAIDS. Available online: https:\/\/www.unaids.org\/en\/resources\/fact-sheet?utm_source=chatgpt.com."},{"key":"ref_2","unstructured":"WHO Regional Office for Europe, and European Centre for Disease Prevention and Control (2025, July 12). HIV\/AIDS Surveillance in Europe 2024\u20132023 Data. Copenhagen: WHO Regional Office for Europe. Available online: https:\/\/www.ecdc.europa.eu\/sites\/default\/files\/documents\/HIV_Surveillance_Report_2024.pdf."},{"key":"ref_3","unstructured":"Institutul Na\u021bional de S\u0103n\u0103tate Public\u0103 (INSP), Rom\u00e2nia (2025, July 12). Analiza Bolilor Transmisibile Aflate \u00een Supraveghere\u2014Raport Pentru Anul 2024, Available online: https:\/\/insp.gov.ro\/download\/analiza-bolilor-transmisibile-aflate-in-supraveghere-raport-pentru-anul-2024\/."},{"key":"ref_4","unstructured":"(2025, July 12). Compartimentul Pentru Monitorizarea \u0219i Evaluarea Infec\u021biei HIV\/SIDA \u00een Rom\u00e2nia\u2014INBI \u201cProf. Dr. M. Bal\u0219\u201d. Rom\u00e2nia la 31 Decembrie 2024: Infec\u021bia HIV\/SIDA\u2014Evolu\u021bie \u0219i Tendin\u021be. Available online: https:\/\/www.cnlas.ro\/images\/doc\/2025\/ROMANIA%20LA%2031%20DECEMBRIE%20-2024%20-%20site.pdf."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Kozinetz, C.A., Matusa, R., and Cazacu, A. (2001). The burden of pediatric HIV\/AIDS in Constanta, Romania: A cross-sectional study. BMC Infect. Dis., 1.","DOI":"10.1186\/1471-2334-1-7"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1097\/00002030-199312000-00012","article-title":"Risk factors for HIV infection among abandoned Romanian children","volume":"7","author":"Hersh","year":"1993","journal-title":"AIDS"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Ruta, S., Grecu, L., Iacob, D., Cernescu, C., and Sultana, C. (2023). HIV-HBV Coinfection\u2014Current Challenges for Virologic Monitoring. Biomedicines, 11.","DOI":"10.3390\/biomedicines11051306"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dagnaw, M., Muche, A.A., Geremew, B.M., and Gezie, L.D. (2025). Prevalence and burden of HBV-HIV co-morbidity: A global systematic review and meta-analysis. Front. Public Health, 13.","DOI":"10.3389\/fpubh.2025.1565621"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1111\/jvh.13899","article-title":"Epidemiology of hepatitis D virus infection in Europe: Is it vanishing?","volume":"31","author":"Demirel","year":"2024","journal-title":"J. Viral Hepat."},{"key":"ref_10","unstructured":"WHO (2025, August 15). Hepatitis B Fact Sheet. Geneva: World Health Organization. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-b?utm_source=chatgpt.com."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"640","DOI":"10.4254\/wjh.v16.i4.640","article-title":"Prospective study of hepatitis B and D epidemiology and risk factors in Romania: A 10-year update","volume":"16","author":"Iacob","year":"2024","journal-title":"World J. Hepatol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Grecu, L.I., Pavel-Tanasa, M., Matei, L., Sultana, C., Ruta, S.M., Grecu, R.I., Ursu, R.G., Cianga, P., and Iancu, L.S. (2024). Molecular Epidemiology of Hepatitis D Virus in the North-East Region of Romania. Pathogens. Pathogens, 13.","DOI":"10.3390\/pathogens13090793"},{"key":"ref_13","unstructured":"WHO (2025, August 15). Global Hepatitis Report 2024: Action for Access in Low- and Middle-Income Countries. Geneva: World Health Organization. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-d?utm_source=chatgpt.com."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/hep.24105","article-title":"Performance of the aspartate aminotransferase-to-platelet ratio index for the staging of hepatitis C-related fibrosis: An updated meta-analysis","volume":"53","author":"Lin","year":"2011","journal-title":"Hepatology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"807","DOI":"10.7326\/0003-4819-158-11-201306040-00005","article-title":"Blood tests to diagnose fibrosis or cirrhosis in patients with chronic hepatitis C virus infection: A systematic review","volume":"158","author":"Chou","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1053\/jhep.2003.50346","article-title":"A simple noninvasive index can predict both significant fibrosis and cirrhosis in patients with chronic hepatitis C","volume":"38","author":"Wai","year":"2003","journal-title":"Hepatology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/hep.21669","article-title":"FIB-4: An inexpensive and accurate marker of fibrosis in HCV infection. comparison with liver biopsy and fibrotest","volume":"46","author":"Mallet","year":"2007","journal-title":"Hepatology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1002\/hep.21178","article-title":"Development of a simple noninvasive index to predict significant fibrosis in patients with HIV\/HCV coinfection","volume":"43","author":"Sterling","year":"2006","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Preda, M., and Manolescu, L.C.S. (2022). Romania, a Harbour of HIV-1 Subtype F1: Where Are We after 33 Years of HIV-1 Infection?. Viruses, 14.","DOI":"10.3390\/v14092081"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Marcu, E.A., Dinescu, S.N., P\u0103dureanu, V., Dumitrescu, F., and Diaconu, R. (2022). Perinatal Exposure to HIV Infection: The Experience of Craiova Regional Centre, Romania. Healthcare, 10.","DOI":"10.3390\/healthcare10020308"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Arbune, M., Calin, A.M., Iancu, A.V., Dumitru, C.N., and Arbune, A.A. (2022). A Real-Life Action toward the End of HIV Pandemic: Surveillance of Mother-to-Child HIV Transmission in a Center from Southeast Romania. J. Clin. Med., 11.","DOI":"10.3390\/jcm11175020"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/1758-2652-7-1-68","article-title":"High prevalence of hepatitis B virus markers in romanian adolescents with human immunodeficiency virus infection","volume":"7","author":"Ruta","year":"2005","journal-title":"J. Int. AIDS Soc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"263","DOI":"10.5152\/balkanmedj.2013.8976","article-title":"Characteristics of Hepatitis B Co-infection and Disease Evolution in HIV-Positive Paediatric Patients in Romania","volume":"30","author":"Arbune","year":"2013","journal-title":"Balk. Med J."},{"key":"ref_24","first-page":"218","article-title":"HBV influence on Response to Antiretroviral Therapy in Horizontally HIV-HBV Coinfected Patient during Early Childhood","volume":"39","author":"Niculescu","year":"2013","journal-title":"Curr. Health Sci. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1586\/eri.13.2","article-title":"HIV\/HBV coinfection in children and antiviral therapy","volume":"11","author":"Healy","year":"2013","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1111\/hiv.13581","article-title":"Hepatitis delta in HIV\/ hepatitis B coinfection: A call for action","volume":"25","author":"Celik","year":"2024","journal-title":"HIV Med."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"P\u0103curar, D., Dinulescu, A., Jugulete, G., P\u0103s\u0103ric\u0103, A.S., and Dijm\u0103rescu, I. (2024). Hepatitis B in Pediatric Population: Observational Retrospective Study in Romania. Life, 14.","DOI":"10.3390\/life14030348"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1016\/j.cld.2023.05.010","article-title":"Triple Threat: HDV, HBV, HIV Coinfection","volume":"27","author":"Yen","year":"2023","journal-title":"Clin. Liver Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Yano, Y., Sato, I., Imanishi, T., Yoshida, R., Matsuura, T., Ueda, Y., and Kodama, Y. (2024). Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen. Diagnostics, 14.","DOI":"10.20944\/preprints202402.0759.v1"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Lungu, G.N., Diaconescu, G.I., Dumitrescu, F., Docea, A.O., Mitrut, R., Giubelan, L., Zlatian, O., and Mitrut, P. (2024). FibroScan\u00ae versus Biochemical Scores: A Study of Liver Fibrosis in HIV with HBV Co-Infection. Microorganisms, 12.","DOI":"10.3390\/microorganisms12061213"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2023). EASL Clinical Practice Guidelines on hepatitis delta virus. J. Hepatol., 79, 433\u2013460.","DOI":"10.1016\/j.jhep.2023.05.001"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1111\/liv.15804","article-title":"Determinants of worse liver-related outcome according to HDV infection among HBsAg positive persons living with HIV: Data from the ICONA cohort","volume":"44","author":"Tavelli","year":"2024","journal-title":"Liver Int."},{"key":"ref_33","unstructured":"European AIDS Clinical Society (2023). EACS Guidelines Version 12.0, European AIDS Clinical Society."},{"key":"ref_34","unstructured":"(2025, November 01). EACS Guidelines Version 13.0. Available online: https:\/\/eacs.sanfordguide.com\/en\/eacs-hiv\/eacs-section4\/hiv-hep-co-infection\/treatment-of-hbv-hiv-co-infection."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101057","DOI":"10.1016\/j.jhepr.2024.101057","article-title":"Treatment with bulevirtide in HIV-infected patients with chronic hepatitis D: ANRS HD EP01 BuleDelta and compassionate cohort","volume":"6","author":"Pol","year":"2024","journal-title":"JHEP Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1111\/jvh.13366","article-title":"Ten-year follow-up of a randomized controlled clinical trial in chronic hepatitis delta","volume":"27","author":"Wranke","year":"2020","journal-title":"J. Viral Hepat."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bardak, A.E., Ozturk, N.B., Gurakar, M., Sequeira, L., Yildiz, E., Ozmert, E.H., Idilman, R., and Gurakar, A. (2025). Updates on Recent Advancements in Hepatitis D Virus Treatment. Viruses. Viruses, 17.","DOI":"10.3390\/v17081100"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Pisaturo, M., Russo, A., Grimaldi, P., Martini, S., and Coppola, N. (2024). Current and future therapeutic options for chronic hepatitis D virus infection. Front. Cell. Infect. Microbiol., 14.","DOI":"10.3389\/fcimb.2024.1382017"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/12\/1261\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T12:39:54Z","timestamp":1765370394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/12\/1261"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":38,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["pathogens14121261"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14121261","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,10]]}}}