{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:53:34Z","timestamp":1760151214511,"version":"build-2065373602"},"reference-count":82,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP 114998"],"award-info":[{"award-number":["MOP 114998"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>We previously characterized a human betaretrovirus and linked infection with the development of primary biliary cholangitis (PBC). There are in vitro and in vivo data demonstrating that antiretroviral therapy used to treat human immunodeficiency virus (HIV) can be repurposed to treat betaretroviruses. As such, PBC patients have been treated with nucleoside\/nucleotide reverse transcriptase inhibitors (NRTIs), alone and in combination with a boosted protease inhibitor or an integrase strand transfer inhibitor in case studies and clinical trials. However, a randomized controlled trial using combination antiretroviral therapy with lopinavir was terminated early because 70% of PBC patients discontinued therapy because of gastrointestinal side effects. In the open-label extension, patients tolerating combination therapy underwent a significant reduction in serum liver parameters, whereas those on NRTIs alone rebounded to baseline. Herein, we compare clinical experience in the experimental use of antiretroviral agents in patients with PBC with the broader experience of using these agents in people living with HIV infection. While the incidence of gastrointestinal side effects in the PBC population appears somewhat increased compared to those with HIV infection, the clinical improvement observed in patients with PBC suggests that further studies using the newer and better tolerated antiretroviral agents are warranted.<\/jats:p>","DOI":"10.3390\/v14030516","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T20:36:30Z","timestamp":1646339790000},"page":"516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Apples to Apples? A Comparison of Real-World Tolerability of Antiretrovirals in Patients with Human Immunodeficiency Virus Infection and Patients with Primary Biliary Cholangitis"],"prefix":"10.3390","volume":"14","author":[{"given":"Shannon","family":"Turvey","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lynora","family":"Saxinger","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Mason","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1002\/hep.30145","article-title":"Primary Biliary Cholangitis: 2018 Practice Guidance from the American Association for the Study of Liver Diseases","volume":"69","author":"Lindor","year":"2019","journal-title":"Hepatology"},{"key":"ref_2","unstructured":"European Association for the Study of the Liver, Hirschfield, G.M., Beuers, U., Corpechot, C., Invernizzi, P., Jones, D., Marzioni, M., and Schramm, C. (2017). EASL Clinical Practice Guidelines: The diagnosis and management of patients with primary biliary cholangitis. J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.bpg.2018.06.001","article-title":"Is PBC a viral infectious disease?","volume":"27e39","author":"Mason","year":"2018","journal-title":"Best Pract. Res. Clin. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/S1089-3261(05)70167-7","article-title":"Autoimmune Liver Disease: Current Standards, Future Directions","volume":"5","author":"Gish","year":"2001","journal-title":"Clin. Liver Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.cld.2008.02.006","article-title":"Other potential medical therapies: The use of antiviral agents to investigate and treat primary ciliary cirrhosis","volume":"12","author":"Mason","year":"2008","journal-title":"Clin. Liver Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1053\/j.gastro.2018.10.001","article-title":"Factors Associated With Recurrence of Primary Biliary Cholangitis After Liver Transplantation and Effects on Graft and Patient Survival","volume":"156","author":"Hansen","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"94","DOI":"10.21926\/obm.transplant.1904094","article-title":"Modelling recurrent primary biliary cholangitis and primary sclerosing cholangitis as infectious diseases following liver transplantation","volume":"3","author":"Dong","year":"2019","journal-title":"OBM Transplant."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1111\/liv.14964","article-title":"Combination antiretroviral therapy improves recurrent primary biliary cholangitis following liver transplantation","volume":"41","author":"Lytvyak","year":"2021","journal-title":"Liver Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/j.1440-1827.2009.02500.x","article-title":"Application of a new histological staging and grading system for primary biliary cirrhosis to liver biopsy specimens: Interobserver agreement","volume":"60","author":"Nakanuma","year":"2010","journal-title":"Pathol. Int."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1080\/1040841X.2018.1501345","article-title":"Human endogenous retrovirus-K (HML-2): A comprehensive review","volume":"44","author":"Henderson","year":"2018","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13100-017-0099-7","article-title":"Identification of a novel HERV-K(HML10): Comprehensive characterization and comparative analysis in non-human primates provide insights about HML10 proviruses structure and diffusion","volume":"8","author":"Grandi","year":"2017","journal-title":"Mob. DNA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/j.jhep.2010.12.009","article-title":"The evidence supports a viral aetiology for primary biliary cirrhosis","volume":"54","author":"Mason","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1002\/hep.20024","article-title":"Cloning the human betaretrovirus proviral genome from patients with primary biliary cirrhosis","volume":"39","author":"Xu","year":"2004","journal-title":"Hepatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1126\/science.84.2172.162.a","article-title":"Some Possible Effects of Nursing on the Mammary Gland Tumor Incidence in Mice","volume":"84","author":"Bittner","year":"1936","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/229611a0","article-title":"Search for a human breast cancer virus","volume":"229","author":"Moore","year":"1971","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1016\/j.ajpath.2011.08.003","article-title":"Mouse mammary tumor virus in human breast cancer red herring or smoking gun?","volume":"179","author":"Mason","year":"2011","journal-title":"Am. J. Pathol."},{"key":"ref_17","first-page":"5173","article-title":"Detection of mammary tumor virus env gene-like sequences in human breast cancer","volume":"55","author":"Wang","year":"1995","journal-title":"Cancer Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5647","DOI":"10.1158\/1078-0432.CCR-04-1234","article-title":"Mouse mammary tumor virus-like viral infection and human breast cancer","volume":"10","author":"Holland","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1016\/S0140-6736(97)10290-2","article-title":"Detection of retroviral antibodies in primary biliary cirrhosis and other idiopathic biliary disorders","volume":"351","author":"Mason","year":"1998","journal-title":"Lancet"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"8454","DOI":"10.1073\/pnas.1433063100","article-title":"Does a betaretrovirus infection trigger primary biliary cirrhosis?","volume":"100","author":"Xu","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1111\/apt.13054","article-title":"Frequent proviral integration of the human betaretrovirus in biliary epithelium of patients with autoimmune and idiopathic liver disease","volume":"41","author":"Wang","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_22","first-page":"8958192","article-title":"Seroprevalence of Human Betaretrovirus Surface Protein Antibodies in Patients with Breast Cancer and Liver Disease","volume":"2020","author":"Zhang","year":"2020","journal-title":"J. Oncol."},{"key":"ref_23","unstructured":"Rahbari, M., Sharon, D., Houghton, M., and Mason, A. (2017, January 3\u20136). Identification of an immunosuppressive domain in human betaretrovirus. Proceedings of the Environment Abstract CDDW Annual Meeting, Banff, AB, Canada."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1126\/science.1210718","article-title":"Successful transmission of a retrovirus depends on the commensal microbiota","volume":"334","author":"Kane","year":"2011","journal-title":"Science"},{"key":"ref_25","first-page":"PO-1822","article-title":"Cellular immune responses to human betaretrovirus in patients with primary biliary cholangitis","volume":"75","author":"Abofayed","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_26","first-page":"84A","article-title":"Isolation of the human betaretrovirus and demonstration of integration sites in patients with primary biliary cirrhosis","volume":"26","author":"Wang","year":"2012","journal-title":"Can. J. Gastroenterol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.1016\/S0140-6736(05)61042-2","article-title":"Expression of pyruvate-dehydrogenase complex PDC-E2 on biliary epithelial cells induced by lymph nodes from primary biliary cirrhosis","volume":"352","author":"Sadamoto","year":"1998","journal-title":"Lancet"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3138\/canlivj.2018-0020","article-title":"Randomized controlled trial: Combination antiretroviral therapy with Tenofovir-Emtricitabine and Lopinavir-Ritonavir in patients with primary biliary cholangitis","volume":"2","author":"Lytvyak","year":"2019","journal-title":"Can. Liver J."},{"key":"ref_29","first-page":"528A","article-title":"Combination Anti-Retroviral Therapy Provides Reduction in Human Betaretrovirus Load and Durable Biochemical Responses in Patients with Primary Biliary Cirrhosis","volume":"62","author":"Lytvyak","year":"2015","journal-title":"Hepatology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"349","DOI":"10.3748\/wjg.v22.i1.349","article-title":"Combination antiretroviral studies for patients with primary biliary cirrhosis","volume":"22","author":"Lytvyak","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1111\/j.1572-0241.2004.40741.x","article-title":"Pilot studies of single and combination antiretroviral therapy in patients with primary biliary cirrhosis","volume":"99","author":"Mason","year":"2004","journal-title":"Am. J. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1111\/j.1365-2036.2008.03799.x","article-title":"Clinical trial: Randomized controlled study of zidovudine and lamivudine for patients with primary biliary cirrhosis stabilized on ursodiol","volume":"28","author":"Mason","year":"2008","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/S0140-6736(10)61343-8","article-title":"Killing two birds with one stone","volume":"377","author":"Schembri","year":"2011","journal-title":"Lancet"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2347","DOI":"10.1084\/jem.180.6.2347","article-title":"Reverse transcriptase-dependent and -independent phases of infection with mouse mammary tumor virus: Implications for superantigen function","volume":"180","author":"Held","year":"1994","journal-title":"J. Exp. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"876","DOI":"10.1016\/j.jhep.2011.01.037","article-title":"Mouse mammary tumor virus in anti-mitochondrial antibody producing mouse models","volume":"55","author":"Zhang","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1111\/liv.12699","article-title":"Impact of combination antiretroviral therapy in the NOD.c3c4 mouse model of autoimmune biliary disease","volume":"35","author":"Sharon","year":"2015","journal-title":"Liver Int."},{"key":"ref_37","first-page":"871","article-title":"Cyclosporine A inhibits in vitro replication of betaretrovirus associated with primary biliary cirrhosis","volume":"30","author":"Wasilenko","year":"2010","journal-title":"Liver Int."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.cgh.2007.11.021","article-title":"A predictive model for fatigue and its etiologic associations in primary biliary cirrhosis","volume":"6","author":"Newton","year":"2008","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_39","unstructured":"(2021). Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring: Recommendations for a Public Health Approach, World Health Organization."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1111\/hiv.12733","article-title":"Adverse effects of chronic treatment with the Main subclasses of highly active antiretroviral therapy: A systematic review","volume":"20","author":"Silva","year":"2019","journal-title":"HIV Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1097\/00126334-200312010-00008","article-title":"Patterns and correlates of discontinuation of the initial HAART regimen in an urban outpatient cohort","volume":"34","author":"Clark","year":"2003","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s12981-020-00328-6","article-title":"Trends and factors associated with modification or discontinuation of the initial antiretroviral regimen during the first year of treatment in the Turkish HIV-TR Cohort, 2011\u20132017","volume":"18","author":"Korten","year":"2021","journal-title":"AIDS Res. Ther."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1007\/s13181-013-0325-8","article-title":"A review of the toxicity of HIV medications","volume":"10","author":"Margolis","year":"2014","journal-title":"J. Med. Toxicol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S0140-6736(02)07873-X","article-title":"Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir","volume":"359","author":"Mallal","year":"2002","journal-title":"Lancet"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1097\/QAI.0000000000000881","article-title":"Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals","volume":"71","author":"Marcus","year":"2016","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Dorjee, K., Baxi, S.M., Reingold, A.L., and Hubbard, A. (2017). Risk of cardiovascular events from current, recent, and cumulative exposure to abacavir among persons living with HIV who were receiving antiretroviral therapy in the United States: A cohort study. BMC Infect. Dis., 17.","DOI":"10.1186\/s12879-017-2808-8"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1093\/cid\/ciz407","article-title":"Greater Weight Gain in Treatment-naive Persons Starting Dolutegravir-based Antiretroviral Therapy","volume":"70","author":"Bourgi","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e25484","DOI":"10.1002\/jia2.25484","article-title":"Weight gain among treatment-na\u00efve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada","volume":"23","author":"Bourgi","year":"2020","journal-title":"J. Int. AIDS Soc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1097\/QAI.0000000000002556","article-title":"Brief Report: Weight Gain Following ART Initiation in ART-Na\u00efve People Living with HIV in the Current Treatment Era","volume":"86","author":"Ruderman","year":"2021","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1097\/COH.0000000000000680","article-title":"Impact of Integrase inhibitors and tenofovir alafenamide on weight gain in people with HIV","volume":"16","author":"Lake","year":"2021","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.antiviral.2009.10.016","article-title":"Understanding and managing the adverse effects of antiretroviral therapy","volume":"85","author":"Hawkins","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_52","first-page":"95","article-title":"HIV protease inhibitors: A review of molecular selectivity and toxicity","volume":"7","author":"Lv","year":"2015","journal-title":"HIV AIDS"},{"key":"ref_53","unstructured":"Administration, F.A.D. (2021, December 24). Kaletra (Lopinavir and Ritonavir) Label, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2016\/021251s052_021906s046lbl.pdf."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1468-1293.2009.00750.x","article-title":"Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-na\u00efve patients","volume":"11","author":"Cicconi","year":"2010","journal-title":"HIV Med."},{"key":"ref_55","unstructured":"U.S. Department of Health and Human Services (2021, December 24). Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV, Available online: https:\/\/clinicalinfo.hiv.gov\/en\/guidelines\/adult-and-adolescent-arv\/whats-new-guidelines."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1097\/QAD.0b013e32832d7350","article-title":"Once-daily darunavir\/ritonavir vs. lopinavir\/ritonavir in treatment-naive, HIV-1-infected patients: 96-week analysis","volume":"23","author":"Mills","year":"2009","journal-title":"Aids"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ijantimicag.2005.03.003","article-title":"Predictive factors of lopinavir\/ritonavir discontinuation for drug-related toxicity: Results from a cohort of 416 multi-experienced HIV-infected individuals","volume":"26","author":"Bongiovanni","year":"2005","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1097\/QAD.0b013e32830285fb","article-title":"Efficacy and safety of once-daily darunavir\/ritonavir versus lopinavir\/ritonavir in treatment-naive HIV-1-infected patients at week 48","volume":"22","author":"Ortiz","year":"2008","journal-title":"Aids"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1056\/NEJMoa012354","article-title":"Lopinavir-ritonavir versus nelfinavir for the initial treatment of HIV infection","volume":"346","author":"Walmsley","year":"2002","journal-title":"N. Engl. J. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1089\/aid.2012.0233","article-title":"Incidence of Hyperbilirubinemia and Jaundice Due to Atazanavir in a Cohort of Hispanic Patients","volume":"29","author":"Bissio","year":"2012","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.2165\/00003495-200969080-00009","article-title":"Atazanavir","volume":"69","author":"Croom","year":"2009","journal-title":"Drugs"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/QAI.0b013e31815ace6a","article-title":"Efficacy and safety of atazanavir, with or without ritonavir, as part of once-daily highly active antiretroviral therapy regimens in antiretroviral-naive patients","volume":"47","author":"Malan","year":"2008","journal-title":"JAIDS J. Acquir. Immune. Defic. Syndr."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1097\/00002030-200312050-00007","article-title":"Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects: 48-week results","volume":"17","author":"Murphy","year":"2003","journal-title":"Aids"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1586\/14787210.6.6.785","article-title":"Atazanavir: Its role in HIV treatment","volume":"6","author":"Wood","year":"2008","journal-title":"Expert Rev. Anti-Infect. Ther."},{"key":"ref_65","first-page":"105","article-title":"Darunavir Stands Up as Preferred HIV Protease Inhibitor","volume":"19","author":"Mallolas","year":"2017","journal-title":"AIDS Rev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1089\/aid.2010.0059","article-title":"Darunavir Outcomes Study: Comparative Effectiveness of Virologic Suppression, Regimen Durability, and Discontinuation Reasons for Three-Class Experienced Patients at 48 Weeks","volume":"26","author":"Willig","year":"2010","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_67","unstructured":"Hsu, R., Brunet, L., Mounzer, K., Fatukasi, T., Fusco, J., Vannappagari, V., Henegar, C., van Wyk, J., Crawford, M., and Curtis, L. (2019). HIV Medicine, Wiley."},{"key":"ref_68","first-page":"1589","article-title":"Effectiveness, durability, and safety of darunavir\/ritonavir in HIV-1-infected patients in routine clinical practice in Italy: A postauthorization noninterventional study","volume":"10","author":"Antinori","year":"2016","journal-title":"Drug Des. Devel."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1111\/j.1468-1293.2012.01060.x","article-title":"Final 192-week efficacy and safety of once-daily darunavir\/ritonavir compared with lopinavir\/ritonavir in HIV-1-infected treatment-na\u00efve patients in the ARTEMIS trial","volume":"14","author":"Orkin","year":"2013","journal-title":"HIV Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e211","DOI":"10.1016\/S2352-3018(18)30021-3","article-title":"Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial","volume":"5","author":"Molina","year":"2018","journal-title":"Lancet HIV"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1016\/S2352-3018(17)30179-0","article-title":"Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): A phase 3, randomised, non-inferiority trial","volume":"5","author":"Orkin","year":"2018","journal-title":"Lancet HIV"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/QCO.0000000000000616","article-title":"Weight gain and integrase inhibitors","volume":"33","author":"Eckard","year":"2020","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"2177","DOI":"10.1093\/jac\/dky145","article-title":"Obesity following ART initiation is common and influenced by both traditional and HIV-\/ART-specific risk factors","volume":"73","author":"Bakal","year":"2018","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1379","DOI":"10.1093\/cid\/ciz999","article-title":"Weight Gain Following Initiation of Antiretroviral Therapy: Risk Factors in Randomized Comparative Clinical Trials","volume":"71","author":"Sax","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s40265-020-01457-y","article-title":"Are New Antiretroviral Treatments Increasing the Risk of Weight Gain?","volume":"81","author":"Shah","year":"2021","journal-title":"Drugs"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1089\/apc.2012.0135","article-title":"A randomized trial of Raltegravir replacement for protease inhibitor or non-nucleoside reverse transcriptase inhibitor in HIV-infected women with lipohypertrophy","volume":"26","author":"Lake","year":"2012","journal-title":"AIDS Patient Care STDS"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.1016\/S0140-6736(14)60084-2","article-title":"Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study","volume":"383","author":"Clotet","year":"2014","journal-title":"Lancet"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3697","DOI":"10.2174\/138161205774580804","article-title":"Hepatotoxicity of antiretroviral drugs","volume":"11","author":"Abrescia","year":"2005","journal-title":"Curr. Pharm. Des."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"S132","DOI":"10.1016\/j.jhep.2005.11.027","article-title":"Hepatotoxicity of antiretrovirals: Incidence, mechanisms and management","volume":"44","year":"2006","journal-title":"J. Hepatol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e00598","DOI":"10.1002\/prp2.598","article-title":"Mechanistic insights into antiretroviral drug-induced liver injury","volume":"8","author":"Pillaye","year":"2020","journal-title":"Pharmacol. Res. Perspect."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Torti, C., Lapadula, G., Casari, S., Puoti, M., Nelson, M., Quiros-Roldan, E., Bella, D., Pastore, G., Ladisa, N., and Minoli, L. (2005). Incidence and risk factors for liver enzyme elevation during highly active antiretroviral therapy in HIV-HCV co-infected patients: Results from the Italian EPOKA-MASTER Cohort. BMC Infect. Dis., 5.","DOI":"10.1186\/1471-2334-5-58"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1086\/427216","article-title":"Influence of liver fibrosis on highly active antiretroviral therapy-associated hepatotoxicity in patients with HIV and hepatitis C virus coinfection","volume":"40","author":"Aranzabal","year":"2005","journal-title":"Clin. Infect. Dis."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/3\/516\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:31:12Z","timestamp":1760135472000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/3\/516"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,3]]},"references-count":82,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["v14030516"],"URL":"https:\/\/doi.org\/10.3390\/v14030516","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2022,3,3]]}}}