Abstract: ORIGINAL ARTICLE Korean J Intern Med 2021;36(Suppl 1):S253-S263 https://doi.org/10.3904/kjim.2020.224 Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019 Ji-Won Kim1, Eun Jin Kim2, Hyun Hee Kwon3, Chi Young Jung2, Kyung Chan Kim2, Jung-Yoon Choe1, and Hyo-Lim Hong 3 Divisions of 1Rheumatology, 2 Pulmonology, and 3Infectious Diseases, Department of Internal Medicine, Daegu Catholic University School of Medicine, Daegu, Korea Received : May 13, 2020 Revised : May 27, 2020 Accepted : May 27, 2020 Correspondence to Hyo-Lim Hong, M.D. Department of Internal Medicine, Daegu Catholic University Medical Center, 33 Duryugongwon-ro 17-gil, Nam-gu, Daegu 42472, Korea Tel: +82-53-650-4899 Fax: +82-53-623-7507 E-mail: hlhong@cu.ac.kr https://orcid.org/0000-00032147-1381 Background/Aims: The efficacies of lopinavir-ritonavir or hydroxychloroquine remain to be determined in patients with coronavirus disease 2019 (COVID-19). To compare the virological and clinical responses to lopinavir-ritonavir and hydroxychloroquine treatment in COVID-19 patients. Methods: This retrospective cohort study included patients with COVID-19 treated with lopinavir-ritonavir or hydroxychloroquine at a single center in Korea from February 17 to March 31, 2020. Patients treated with lopinavir-ritonavir and hydroxychloroquine concurrently and those treated with lopinavir-ritonavir or hydroxychloroquine for less than 7 days were excluded. Time to negative conversion of viral RNA, time to clinical improvement, and safety outcomes were assessed after 6 weeks of follow-up. Results: Of 65 patients (mean age, 64.3 years; 25 men [38.5%]), 31 were treated with lopinavir-ritonavir and 34 were treated with hydroxychloroquine. The median duration of symptoms before treatment was 7 days and 26 patients (40%) required oxygen support at baseline. Patients treated with lopinavir-ritonavir had a significantly shorter time to negative conversion of viral RNA than those treated with hydroxychloroquine (median, 21 days vs. 28 days). Treatment with lopinavir-ritonavir (adjusted hazard ratio [aHR], 2.28; 95% confidence interval [CI], 1.24 to 4.21) and younger age (aHR, 2.64; 95% CI 1.43 to 4.87) was associated with negative conversion of viral RNA. There was no significant difference in time to clinical improvement between lopinavir-ritonavir- and hydroxychloroquine-treated patients (median, 18 days vs. 21 days). Lymphopenia and hyperbilirubinemia were more frequent in lopinavir-ritonavir-treated patients compared with hydroxychloroquine-treated patients. Conclusions: Lopinavir-ritonavir was associated with more rapid viral clearance than hydroxychloroquine in mild to moderate COVID-19, despite comparable clinical responses. These findings should be confirmed in randomized, controlled trials. Keywords: COVID-19; Severe acute respiratory syndrome coronavirus 2; Lopinavir-ritonavir; Hydroxychloroquine Copyright © 2021 The Korean Association of Internal Medicine This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. pISSN 1226-3303 eISSN 2005-6648 http://www.kjim.org The Korean Journal of Internal Medicine Vol. 36, Suppl 1, March..