{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:58:52Z","timestamp":1793051932486,"version":"4.5.0"},"reference-count":115,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,11]],"date-time":"2021-07-11T00:00:00Z","timestamp":1625961600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009060","name":"Sidaction","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100009060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003323","name":"Agence Nationale de Recherches sur le Sida et les H\u00e9patites Virales","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100003323","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>In individuals infected with hepatitis B virus (HBV), the loss of hepatitis B surface antigen (HBsAg) is the ultimate therapeutic goal, which defines \u201cfunctional cure.\u201d For individuals living with human immunodeficiency virus (HIV), functional cure occurs roughly 2 per 100 person-years during potent anti-HBV containing antiretroviral therapy. Although this rate may be higher than expected in treated HBV mono-infected individuals, rates of functional cure widely vary between studies (0.6\u201310.5 per 100 person-years). Similar to HBV mono-infection, the phase of HBV infection, HBV (sub-)genotypes and hepatitis B \u201ce\u201d Ag-negative variants are associated with functional cure in treated HIV-HBV co-infection. In specifically HIV-HBV co-infected individuals, strong increases in CD4+ T cell counts after treatment initiation have also been linked to functional cure, yet this finding is inconsistent across studies. Several markers directly or indirectly reflecting HBV activity are being developed to predict functional cure, such as quantification of HBsAg, hepatitis B core-related antigen, HBsAg protein composition, anti-hepatitis B core antibodies and interferon-gamma-inducible protein 10. Few have been assessed during treatment in HIV-HBV co-infected individuals and none have been validated to predict functional cure. Novel therapeutics for HBV cure are essential for individuals with HIV-HBV co-infection and need to be separately evaluated in this population.<\/jats:p>","DOI":"10.3390\/v13071341","type":"journal-article","created":{"date-parts":[[2021,7,11]],"date-time":"2021-07-11T22:16:48Z","timestamp":1626041808000},"page":"1341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Functional Cure of Hepatitis B Virus Infection in Individuals With HIV-Coinfection: A Literature Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9512-8928","authenticated-orcid":false,"given":"Anders","family":"Boyd","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Research and Prevention, Public Health Service of Amsterdam, 1018 WT Amsterdam, The Netherlands"},{"name":"Stichting HIV Monitoring, 1105 BD Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza N. C.","family":"Dezanet","sequence":"additional","affiliation":[{"name":"Institut Pierre Louis d\u2019\u00c9pid\u00e9miologie et de Sant\u00e9 Publique, INSERM, IPLESP, Sorbonne Universit\u00e9, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Lacombe","sequence":"additional","affiliation":[{"name":"Institut Pierre Louis d\u2019\u00c9pid\u00e9miologie et de Sant\u00e9 Publique, INSERM, IPLESP, Sorbonne Universit\u00e9, 75012 Paris, France"},{"name":"APHP, H\u00f4pital Saint-Antoine, Service de Maladies Infectieuses et Tropicales, 75012 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2799","DOI":"10.1093\/cid\/ciz1170","article-title":"Global burden of hepatitis b infection in people living with human immunodeficiency virus: A systematic review and meta-analysis","volume":"71","author":"Leumi","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1093\/cid\/cis432","article-title":"Comparative risk of liver-related mortality from chronic hepatitis B versus chronic hepatitis C virus infection","volume":"55","author":"Seaberg","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nina Kim, H., Newcomb, C.W., Carbonari, D.M., Roy, J.A., Torgersen, J., Althoff, K.N., Kitahata, M.M., Rajender Reddy, K., Lim, J.K., and Silverberg, M.J. (2021). Risk of Hepatocellular carcinoma with hepatitis B viremia among HIV\/hepatitis B virus-coinfected persons in North America. Hepatology.","DOI":"10.1002\/hep.31839"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1097\/01.aids.0000218550.85081.59","article-title":"Characteristics of drug resistant HBV in an international collaborative study of HIV-HBV-infected individuals on extended lamivudine therapy","volume":"20","author":"Matthews","year":"2006","journal-title":"AIDS"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"643","DOI":"10.3851\/IMP2959","article-title":"Low risk of lamivudine-resistant HBV and hepatic flares in treated HIV-HBV-coinfected patients from Cote d\u2019Ivoire","volume":"20","author":"Boyd","year":"2015","journal-title":"Antivir. Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/QAI.0000000000000927","article-title":"Lamivudine monotherapy-based cART is efficacious for HBV treatment in HIV\/HBV coinfection when baseline HBV DNA <20,000 IU\/mL","volume":"72","author":"Li","year":"2016","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1097\/QAD.0000000000000686","article-title":"Comparison of HBV-active HAART regimens in an HIV-HBV multinational cohort: Outcomes through 144 weeks","volume":"29","author":"Thio","year":"2015","journal-title":"AIDS"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/hep.27182","article-title":"Persistent viremia in human immunodeficiency virus\/hepatitis B coinfected patients undergoing long-term tenofovir: Virological and clinical implications","volume":"60","author":"Boyd","year":"2014","journal-title":"Hepatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1097\/QAI.0000000000001069","article-title":"Brief report: Efficacy and safety of switching to a single-tablet regimen of elvitegravir\/cobicistat\/emtricitabine\/tenofovir alafenamide in HIV-1\/hepatitis B-coinfected adults","volume":"73","author":"Gallant","year":"2016","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"21426","DOI":"10.7448\/IAS.20.1.21426","article-title":"Liver fibrosis regression and progression during controlled hepatitis B virus infection among HIV-HBV patients treated with tenofovir disoproxil fumarate in France: A prospective cohort study","volume":"20","author":"Boyd","year":"2017","journal-title":"J. Int. AIDS Soc."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/S0140-6736(12)61425-1","article-title":"Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: A 5-year open-label follow-up study","volume":"381","author":"Marcellin","year":"2013","journal-title":"Lancet"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sterling, R.K., King, W.C., Khalili, M., Chung, R.T., Sulkowski, M., Jain, M.K., Lisker-Melman, M., Ghany, M.G., Wong, D.K., and Hinerman, A.S. (2021). A prospective study evaluating changes in histology, clinical and virologic outcomes in HBV-HIV co-infected adults in North America. Hepatology.","DOI":"10.1002\/hep.31823"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2017). EASL 2017 clinical practice guidelines on the management of hepatitis B virus infection. J. Hepatol., 67, 370\u2013398.","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.jcv.2012.01.003","article-title":"Variable capacity of 13 hepatitis B virus surface antigen assays for the detection of HBsAg mutants in blood samples","volume":"53","author":"Ly","year":"2012","journal-title":"J. Clin. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/j.jhep.2019.11.003","article-title":"Guidance for design and endpoints of clinical trials in chronic hepatitis B\u2014Report from the 2019 EASL-AASLD HBV Treatment Endpoints Conference","volume":"72","author":"Cornberg","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1097\/QAD.0b013e328334bddb","article-title":"Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption","volume":"24","author":"Dore","year":"2010","journal-title":"AIDS"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1111\/liv.12521","article-title":"Use of hepatitis B surface and \u201ce\u201d antigen quantification during extensive treatment with tenofovir in patients co-infected with HIV-HBV","volume":"35","author":"Boyd","year":"2015","journal-title":"Liver Int."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1111\/jgh.13156","article-title":"Hepatitis B surface antigen quantification as a predictor of seroclearance during treatment in HIV-hepatitis B virus coinfected patients from Sub-Saharan Africa","volume":"31","author":"Boyd","year":"2016","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1093\/infdis\/jiz450","article-title":"High rates of hepatitis B virus (HBV) functional cure among human immunodeficiency virus-HBV coinfected patients on antiretroviral therapy in Zambia","volume":"221","author":"Chihota","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s12072-019-09953-4","article-title":"Long-term virological and serologic responses of chronic hepatitis B virus infection to tenofovir disoproxil fumarate-containing regimens in patients with HIV and hepatitis B coinfection","volume":"13","author":"Huang","year":"2019","journal-title":"Hepatol. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1111\/j.1365-2893.2012.01601.x","article-title":"Five-year on-treatment efficacy of lamivudine-, tenofovir- and tenofovir + emtricitabine-based HAART in HBV-HIV-coinfected patients","volume":"19","author":"Kosi","year":"2012","journal-title":"J. Viral Hepat."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1097\/QAD.0b013e328340fde2","article-title":"Clinical and virological outcomes in HIV-infected patients with chronic hepatitis B on long-term nucleos(t)ide analogues","volume":"25","author":"Teixeira","year":"2011","journal-title":"AIDS"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Matthews, G.V., Ali, R.J., Avihingsanon, A., Amin, J., Hammond, R., Bowden, S., Lewin, S.R., Sasadeusz, J., Littlejohn, M., and Locarnini, S.L. (2013). Quantitative HBsAg and HBeAg predict hepatitis B seroconversion after initiation of HAART in HIV-HBV coinfected individuals. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061297"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1097\/QAD.0b013e32810c8bcf","article-title":"Epidemiology, diagnosis and treatment of chronic hepatitis B in HIV-infected patients (EPIB 2005 STUDY)","volume":"21","author":"Piroth","year":"2007","journal-title":"AIDS"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1111\/jvh.12175","article-title":"Viral determinants predicting hepatitis B surface antigen (HBsAg) seroclearance in HIV-\/HBV-coinfected patients","volume":"21","author":"Strassl","year":"2014","journal-title":"J. Viral Hepat."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Dezanet, L.N.C., Miailhes, P., Lascoux-Combe, C., Chas, J., Maylin, S., Gabassi, A., Rougier, H., Delaugerre, C., Lacombe, K., and Boyd, A. (2021). Persistent HBV replication and serological response during up to fifteen years of tenofovir-based antiretroviral therapy in HIV-hepatitis B coinfected patients: A multicenter prospective cohort study. MedRxiv.","DOI":"10.1101\/2021.07.01.21259560"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1093\/infdis\/jis439","article-title":"Hepatitis B surface antigen declines and clearance during long-term tenofovir therapy in patients coinfected with HBV and HIV","volume":"206","author":"Zoutendijk","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1086\/520752","article-title":"Impact of highly active antiretroviral therapy (HAART) on the natural history of hepatitis B virus (HBV) and HIV coinfection: Relationship between prolonged efficacy of HAART and HBV surface and early antigen seroconversion","volume":"45","author":"Miailhes","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2978","DOI":"10.1111\/liv.14684","article-title":"Obstacles to HBV functional cure: Late presentation in HIV and its impact on HBV seroconversion in HIV\/HBV coinfection","volume":"40","author":"Hoffmann","year":"2020","journal-title":"Liver Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1097\/QAI.0000000000002386","article-title":"Long-term TDF-inclusive ART and Progressive rates of HBsAg loss in HIV-HBV coinfection-lessons for functional HBV cure?","volume":"84","author":"Audsley","year":"2020","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.jcv.2017.08.008","article-title":"Development of anti-hepatitis B surface (HBs) antibodies after HBs antigen loss in HIV-hepatitis B virus co-infected patients","volume":"95","author":"Boyd","year":"2017","journal-title":"J. Clin. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.jhep.2017.11.039","article-title":"96weeks treatment of tenofovir alafenamide vs. tenofovir disoproxil fumarate for hepatitis B virus infection","volume":"68","author":"Agarwal","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1007\/s10620-014-3486-7","article-title":"Seven-year efficacy and safety of treatment with tenofovir disoproxil fumarate for chronic hepatitis B virus infection","volume":"60","author":"Buti","year":"2015","journal-title":"Dig. Dis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1053\/j.gastro.2013.12.028","article-title":"Randomized comparison of tenofovir disoproxil fumarate vs. emtricitabine and tenofovir disoproxil fumarate in patients with lamivudine-resistant chronic hepatitis B","volume":"146","author":"Fung","year":"2014","journal-title":"Gastroenterology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.jhep.2012.04.037","article-title":"Long-term continuous entecavir therapy in nucleos(t)ide-naive chronic hepatitis B patients","volume":"57","author":"Ono","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_36","first-page":"305","article-title":"Effectiveness of entecavir treatment and predictive factors for virologic response","volume":"106","author":"Preda","year":"2014","journal-title":"Rev. Esp. Enferm. Dig."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1007\/s10620-017-4448-7","article-title":"Effectiveness and safety of entecavir or tenofovir in a Spanish cohort of chronic hepatitis B patients: Validation of the page-B score to predict hepatocellular carcinoma","volume":"62","author":"Tabernero","year":"2017","journal-title":"Dig. Dis. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.jhep.2013.11.024","article-title":"Long-term efficacy and safety of emtricitabine plus tenofovir DF vs. tenofovir DF monotherapy in adefovir-experienced chronic hepatitis B patients","volume":"60","author":"Berg","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/hep.28916","article-title":"Low-level viremia and the increased risk of hepatocellular carcinoma in patients receiving entecavir treatment","volume":"66","author":"Kim","year":"2017","journal-title":"Hepatology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/hep.23327","article-title":"Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B","volume":"51","author":"Chang","year":"2010","journal-title":"Hepatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.jhep.2009.12.036","article-title":"Long-term use of entecavir in nucleoside-naive Japanese patients with chronic hepatitis B infection","volume":"52","author":"Yokosuka","year":"2010","journal-title":"J. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/hepr.12427","article-title":"Risk of hepatocellular carcinoma in cirrhotic hepatitis B virus patients during nucleoside\/nucleotide analog therapy","volume":"45","author":"Orito","year":"2015","journal-title":"Hepatol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/S2468-1253(16)30107-8","article-title":"Tenofovir alafenamide versus tenofovir disoproxil fumarate for the treatment of patients with HBeAg-negative chronic hepatitis B virus infection: A randomised, double-blind, phase 3, non-inferiority trial","volume":"1","author":"Buti","year":"2016","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1136\/gutjnl-2013-305517","article-title":"HBsAg seroclearance after nucleoside analogue therapy in patients with chronic hepatitis B: Clinical outcomes and durability","volume":"63","author":"Kim","year":"2014","journal-title":"Gut"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1868","DOI":"10.1111\/liv.14155","article-title":"Ten-year efficacy and safety of tenofovir disoproxil fumarate treatment for chronic hepatitis B virus infection","volume":"39","author":"Marcellin","year":"2019","journal-title":"Liver Int."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3072","DOI":"10.1007\/s10620-015-4027-8","article-title":"Effectiveness and safety of tenofovir disoproxil fumarate in chronic hepatitis B: A 3-year, prospective, real-world study in France","volume":"61","author":"Marcellin","year":"2016","journal-title":"Dig. Dis. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1002\/hep.26376","article-title":"Reduction of hepatitis B surface antigen levels and hepatitis B surface antigen seroclearance in chronic hepatitis B patients receiving 10 years of nucleoside analogue therapy","volume":"58","author":"Seto","year":"2013","journal-title":"Hepatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1002\/jgh3.12321","article-title":"Clinical features of chronic hepatitis B patients with low hepatitis B surface antigen levels and determinants of hepatitis B surface antigen seroclearance","volume":"4","author":"Taniguchi","year":"2020","journal-title":"JGH Open"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1097\/QAD.0b013e328352224d","article-title":"Kinetics of hepatitis B surface and e antigen and prediction of treatment response to tenofovir in antiretroviral-experienced HIV-hepatitis B virus-infected patients","volume":"26","author":"Maylin","year":"2012","journal-title":"AIDS"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"i47","DOI":"10.1136\/gutjnl-2012-302062","article-title":"HIV and viral hepatitis coinfections: Advances and challenges","volume":"61","author":"Lacombe","year":"2012","journal-title":"Gut"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Gantner, P., Cotte, L., Allavena, C., Bani-Sadr, F., Huleux, T., Duvivier, C., Valantin, M.A., Jacomet, C., Joly, V., and Cheret, A. (2019). Higher rates of HBsAg clearance with tenofovir-containing therapy in HBV\/HIV co-infection. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0215464"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/jvh.13212","article-title":"Long-term observation on hepatitis B surface antigen seroclearance in therapy experienced HIV\/HBV co-infected Chinese","volume":"27","author":"Yang","year":"2020","journal-title":"J. Viral Hepat."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"a021436","DOI":"10.1101\/cshperspect.a021436","article-title":"Hepatitis B virus genotypes and variants","volume":"5","author":"Lin","year":"2015","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1136\/gutjnl-2015-309300","article-title":"Deep sequencing shows that HBV basal core promoter and precore variants reduce the likelihood of HBsAg loss following tenofovir disoproxil fumarate therapy in HBeAg-positive chronic hepatitis B","volume":"66","author":"Bayliss","year":"2017","journal-title":"Gut"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1111\/jvh.12914","article-title":"Precore G1896A mutation is associated with reduced rates of HBsAg seroclearance in treated HIV hepatitis B virus co-infected patients from western Africa","volume":"25","author":"Boyd","year":"2018","journal-title":"J. Viral Hepat."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1136\/gutjnl-2012-302408","article-title":"Cumulative viral evolutionary changes in chronic hepatitis B virus infection precedes hepatitis B e antigen seroconversion","volume":"62","author":"Cheng","year":"2013","journal-title":"Gut"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1002\/jmv.21049","article-title":"Relationship of serological subtype, basic core promoter and precore mutations to genotypes\/subgenotypes of hepatitis B virus","volume":"80","author":"Kramvis","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.jhep.2016.01.027","article-title":"Overview of hepatitis B viral replication and genetic variability","volume":"64","author":"Tong","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"493","DOI":"10.3851\/IMP1495","article-title":"Drug-resistant and immune-escape HBV mutants in HIV-infected hosts","volume":"15","author":"Lacombe","year":"2010","journal-title":"Antivir. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jcv.2017.08.001","article-title":"The variability of hepatitis B envelope is associated with HBs antigen persistence in either chronic or acute HBV genotype A infection","volume":"94","author":"Eschlimann","year":"2017","journal-title":"J. Clin. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/jvh.12498","article-title":"Characterization of hepatitis B virus surface antigen variability and impact on HBs antigen clearance under nucleos(t)ide analogue therapy","volume":"23","author":"Velay","year":"2016","journal-title":"J. Viral Hepat."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.virusres.2015.08.004","article-title":"HBsAg sT123N mutation induces stronger antibody responses to HBsAg and HBcAg and accelerates in vivo HBsAg clearance","volume":"210","author":"Li","year":"2015","journal-title":"Virus Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1111\/liv.13975","article-title":"Effect of hepatitis B virus (HBV) surface-gene variability on markers of replication during treated human immunodeficiency virus-HBV infection in Western Africa","volume":"39","author":"Boyd","year":"2019","journal-title":"Liver Int."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1111\/liv.14008","article-title":"Association of HLA-DPA1 and HLA-DPB1 polymorphisms with spontaneous HBsAg seroclearance in Caucasians","volume":"39","author":"Koukoulioti","year":"2019","journal-title":"Liver Int."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1111\/liv.12652","article-title":"HLA-DP genes polymorphisms associate with hepatitis B surface antigen kinetics and seroclearance during nucleot(s)ide analogue therapy","volume":"35","author":"Hosaka","year":"2015","journal-title":"Liver Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"104663","DOI":"10.1016\/j.meegid.2020.104663","article-title":"Human genetic susceptibility to hepatitis B virus infection","volume":"87","author":"Xu","year":"2021","journal-title":"Infect. Genet. Evol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12737","DOI":"10.1038\/s41598-018-31065-6","article-title":"Polymorphisms in the Toll-like receptor 3 (TLR3) gene are associated with the natural course of hepatitis B virus infection in Caucasian population","volume":"8","author":"Fischer","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.ijid.2020.04.079","article-title":"Genetic variation in IL-10 influences the progression of hepatitis B infection","volume":"96","author":"Rybicka","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Liao, J., Zhang, Q., Liao, Y., Cai, B., Chen, J., Li, L., and Wang, L. (2014). Association of T-cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) polymorphisms with susceptibility and disease progression of HBV infection. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0098280"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1086\/657146","article-title":"IL28B polymorphism does not determine outcomes of hepatitis B virus or HIV infection","volume":"202","author":"Martin","year":"2010","journal-title":"J. Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.humimm.2020.01.003","article-title":"The HLA-G 14-bp insertion\/deletion polymorphism is associated with chronic hepatitis B in Southern Brazil: A case-control study","volume":"81","author":"Stumm","year":"2020","journal-title":"Hum. Immunol."},{"key":"ref_72","unstructured":"Yoshikawa, S., Yoshio, S., Yoshida, Y., Tsutsui, Y., Kawai, H., Yamazoe, T., Mori, T., Osawa, Y., Sugiyama, M., and Iwamoto, M. (2020). Impact of immune reconstitution-induced hepatic flare on HBsAg loss in HBV\/HIV-1-coinfected patients. J. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.jhep.2020.04.013","article-title":"Hepatitis B surface antigen seroclearance: Immune mechanisms, clinical impact, importance for drug development","volume":"73","author":"Tout","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/QAD.0b013e3283410ccb","article-title":"Increased intrahepatic apoptosis but reduced immune activation in HIV-HBV co-infected patients with advanced immunosuppression","volume":"25","author":"Iser","year":"2011","journal-title":"AIDS"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1053\/j.gastro.2018.11.037","article-title":"New and old biomarkers for diagnosis and management of chronic hepatitis B virus infection","volume":"156","author":"Coffin","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"104553","DOI":"10.1016\/j.antiviral.2019.104553","article-title":"Non-invasive biomarkers for chronic hepatitis B virus infection management","volume":"169","author":"Charre","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1002\/hep.23571","article-title":"Serum hepatitis B surface antigen and hepatitis B e antigen titers: Disease phase influences correlation with viral load and intrahepatic hepatitis B virus markers","volume":"51","author":"Thompson","year":"2010","journal-title":"Hepatology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1136\/gutjnl-2011-301096","article-title":"Quantification of serum hepatitis B surface antigen: Is it useful for the management of chronic hepatitis B?","volume":"61","author":"Janssen","year":"2012","journal-title":"Gut"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.jhep.2016.05.014","article-title":"Decay of ccc-DNA marks persistence of intrahepatic viral DNA synthesis under tenofovir in HIV-HBV co-infected patients","volume":"65","author":"Boyd","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1111\/liv.12075","article-title":"The role of HBsAg quantification for monitoring natural history and treatment outcome","volume":"33","author":"Lapalus","year":"2013","journal-title":"Liver Int."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1128\/jvi.52.2.396-402.1984","article-title":"Large surface proteins of hepatitis B virus containing the pre-s sequence","volume":"52","author":"Heermann","year":"1984","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1136\/gutjnl-2017-313811","article-title":"Quantification of large and middle proteins of hepatitis B virus surface antigen (HBsAg) as a novel tool for the identification of inactive HBV carriers","volume":"67","author":"Pfefferkorn","year":"2018","journal-title":"Gut"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jhep.2020.08.039","article-title":"Composition of HBsAg is predictive of HBsAg loss during treatment in patients with HBeAg-positive chronic hepatitis B","volume":"74","author":"Pfefferkorn","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1046\/j.1365-2893.2003.00437.x","article-title":"Clinical evaluation of a new enzyme immunoassay for hepatitis B virus core-related antigen; a marker distinct from viral DNA for monitoring lamivudine treatment","volume":"10","author":"Rokuhara","year":"2003","journal-title":"J. Viral Hepat."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.jhep.2018.11.030","article-title":"Serum hepatitis B core-related antigen (HBcrAg) correlates with covalently closed circular DNA transcriptional activity in chronic hepatitis B patients","volume":"70","author":"Testoni","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1097\/QAD.0000000000002659","article-title":"Correlation of serum hepatitis B core-related antigen with hepatitis B virus total intrahepatic DNA and covalently closed circular-DNA viral load in HIV-hepatitis B coinfection","volume":"34","author":"Dezanet","year":"2020","journal-title":"AIDS"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1111\/liv.13046","article-title":"Serum hepatitis B core-related antigen as a treatment predictor of pegylated interferon in patients with HBeAg-positive chronic hepatitis B","volume":"36","author":"Chuaypen","year":"2016","journal-title":"Liver Int."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1111\/jvh.13097","article-title":"Relationship between hepatitis B core-related antigen levels and sustained HBeAg seroconversion in patients treated with nucleo(s)tide analogues","volume":"26","author":"Sonneveld","year":"2019","journal-title":"J. Viral Hepat."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1093\/infdis\/jiaa013","article-title":"Kinetics of Hepatitis B Core-Related Antigen and Anti-Hepatitis B Core Antibody and Their Association With Serological Response in Human Immunodeficiency Virus-Hepatitis B Coinfection","volume":"221","author":"Dezanet","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1053\/j.gastro.2007.06.057","article-title":"Impaired intrahepatic hepatitis B virus productivity contributes to low viremia in most HBeAg-negative patients","volume":"133","author":"Volz","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.jhep.2016.09.028","article-title":"Serum HBV pgRNA as a clinical marker for cccDNA activity","volume":"66","author":"Giersch","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1002\/hep.27381","article-title":"Serum hepatitis B virus RNA levels as an early predictor of hepatitis B e antigen seroconversion during treatment with polymerase inhibitors","volume":"61","author":"Bartens","year":"2015","journal-title":"Hepatology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1093\/infdis\/jiy270","article-title":"Serum HBV RNA as a predictor of peginterferon Alfa-2a response in patients with HBeAg-positive chronic hepatitis B","volume":"218","author":"Krauel","year":"2018","journal-title":"J. Infect. Dis."},{"key":"ref_94","first-page":"45","article-title":"Expression of CXC chemokine IP-10 in patients with chronic hepatitis B","volume":"7","author":"Wang","year":"2008","journal-title":"Hepatobiliary Pancreat. Dis. Int."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1111\/j.1365-2893.2012.01611.x","article-title":"T-cell responses to hepatitis B splice-generated protein of hepatitis B virus and inflammatory cytokines\/chemokines in chronic hepatitis B patients. ANRS study: HB EP 02 HBSP-FIBRO","volume":"19","author":"Bayard","year":"2012","journal-title":"J. Viral Hepat."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"898","DOI":"10.1016\/j.jhep.2013.01.029","article-title":"Serum levels of interferon-gamma-inducible protein 10 and response to peginterferon therapy in HBeAg-positive chronic hepatitis B","volume":"58","author":"Sonneveld","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.antiviral.2014.01.001","article-title":"Predictive value of interferon-gamma inducible protein 10 kD for hepatitis B e antigen clearance and hepatitis B surface antigen decline during pegylated interferon alpha therapy in chronic hepatitis B patients","volume":"103","author":"Wang","year":"2014","journal-title":"Antivir. Res."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1016\/j.jhep.2013.08.023","article-title":"Changes of HBsAg and interferon-inducible protein 10 serum levels in naive HBeAg-negative chronic hepatitis B patients under 4-year entecavir therapy","volume":"60","author":"Papatheodoridis","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1111\/hiv.12257","article-title":"Soluble biomarkers of immune activation and inflammation in HIV infection: Impact of 2 years of effective first-line combination antiretroviral therapy","volume":"16","author":"Hattab","year":"2015","journal-title":"HIV Med."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Noel, N., Lerolle, N., Lecuroux, C., Goujard, C., Venet, A., Saez-Cirion, A., Avettand-Fenoel, V., Meyer, L., Boufassa, F., and Lambotte, O. (2015). Immunologic and virologic progression in HIV controllers: The role of viral \u201cBlips\u201d and immune activation in the ANRS CO21 CODEX study. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0131922"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1097\/01.aids.0000432455.06476.bc","article-title":"HIV-1 infection induces strong production of IP-10 through TLR7\/9-dependent pathways","volume":"27","author":"Simmons","year":"2013","journal-title":"AIDS"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"429","DOI":"10.3851\/IMP2720","article-title":"CXCL-10, interleukin-12 and interleukin-21 are not immunological predictors of HBeAg seroconversion in HIV-1-HBV coinfection following HBV-active antiretroviral therapy","volume":"19","author":"Giarda","year":"2014","journal-title":"Antivir. Ther."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1136\/gutjnl-2012-302656","article-title":"Quantitative hepatitis B core antibody level may help predict treatment response in chronic hepatitis B patients","volume":"62","author":"Yuan","year":"2013","journal-title":"Gut"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1136\/gutjnl-2014-308546","article-title":"Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues","volume":"65","author":"Fan","year":"2016","journal-title":"Gut"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1172\/JCI45685","article-title":"Attenuation of HIV-associated human B cell exhaustion by siRNA downregulation of inhibitory receptors","volume":"121","author":"Kardava","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"ofaa215","DOI":"10.1093\/ofid\/ofaa215","article-title":"Association of hepatitis B core-related antigen and antihepatitis B core antibody with liver fibrosis evolution in human immunodeficiency virus-hepatitis B virus coinfected patients during treatment with tenofovir","volume":"7","author":"Cruchet","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1002\/hep.27586","article-title":"Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study)","volume":"61","author":"Brouwer","year":"2015","journal-title":"Hepatology"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S2468-1253(16)30189-3","article-title":"Effect on HBs antigen clearance of addition of pegylated interferon alfa-2a to nucleos(t)ide analogue therapy versus nucleos(t)ide analogue therapy alone in patients with HBe antigen-negative chronic hepatitis B and sustained undetectable plasma hepatitis B virus DNA: A randomised, controlled, open-label trial","volume":"2","author":"Bourliere","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s12072-019-09989-6","article-title":"Finite nucleos(t)ide analog therapy in HBeAg-negative chronic hepatitis B: An emerging paradigm shift","volume":"13","author":"Liaw","year":"2019","journal-title":"Hepatol. Int."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1111\/jvh.12581","article-title":"Intensification with pegylated interferon during treatment with tenofovir in HIV-hepatitis B virus co-infected patients","volume":"23","author":"Boyd","year":"2016","journal-title":"J. Viral Hepat."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.4269\/ajtmh.16-1016","article-title":"Clinical outcomes during treatment interruptions in human immunodeficiency virus-hepatitis B virus co-infected patients from Sub-Saharan Africa","volume":"97","author":"Boyd","year":"2017","journal-title":"Am. J. Trop. Med. Hyg."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jhep.2019.03.034","article-title":"Update of the statements on biology and clinical impact of occult hepatitis B virus infection","volume":"71","author":"Raimondo","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/liv.14364","article-title":"Can we cure hepatitis B virus with novel direct-acting antivirals?","volume":"40","author":"Martinez","year":"2020","journal-title":"Liver Int."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1111\/liv.14371","article-title":"Will we need novel combinations to cure HBV infection?","volume":"40","author":"Dusheiko","year":"2020","journal-title":"Liver Int."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1177\/135965350901400207","article-title":"The pathogenesis of liver disease in the setting of HIV-hepatitis B virus coinfection","volume":"14","author":"Iser","year":"2009","journal-title":"Antivir. Ther."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/7\/1341\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:29:04Z","timestamp":1760164144000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/13\/7\/1341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,11]]},"references-count":115,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7]]}},"alternative-id":["v13071341"],"URL":"https:\/\/doi.org\/10.3390\/v13071341","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,11]]}}}