{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T15:22:52Z","timestamp":1765380172019,"version":"3.38.0"},"reference-count":41,"publisher":"University of Toronto Press Inc. (UTPress)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Canadian Liver Journal"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p> Background: Prior studies using reverse transcriptase inhibitors to treat a human betaretrovirus (HBRV) in patients with primary biliary cholangitis (PBC) resulted in a 21% reduction in alkaline phosphatase (ALP). Herein, we studied the safety and efficacy of combination tenofovir-emtricitabine (TDF\/FTC) and lopinavir-ritonavir (LPRr) in PBC patients unresponsive to ursodeoxycholic acid (UDCA). Methods: A double-blind randomized controlled trial was performed in patients on UDCA for 6 months or more with ALP levels greater than two-fold the upper limit of normal or bilirubin greater than the upper limit of normal. Patients were randomized to daily TDF\/FTC 300\/200 mg and LPRr 800\/200 mg versus identical placebo for 6 months. The primary endpoint was reduction of ALP below 1.67 \u00d7 ULN or normalization of bilirubin. HBRV DNA levels were assessed in peripheral blood mononuclear cells (PBMC) using digital droplet polymerase chain reaction. Results: The enrolment was limited to 13 patients because most patients were unable to tolerate LPRr due to the development of gastrointestinal symptoms. No difference in the primary endpoint was achieved. A significant reduction was observed in ALP by 25% ( P &lt; 0.05) and in HBRV proviral load ( P &lt; 0.05) after 6 months of combination antiretroviral therapy. The majority of patients had diminished levels of LPRr after 6 months\u2019 therapy suggesting inadequate intake of protease inhibitor toward the end of the study. Conclusions: Combination anti-retroviral therapy resulted in improvement in hepatic biochemistry with reduction in proviral load. The frequency of side effects from LPRr in patients with PBC exceeds the frequency reported for HIV, warranting the search for better tolerated combinations in future studies. <\/jats:p>","DOI":"10.3138\/canlivj.2018-0020","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T21:36:05Z","timestamp":1547069765000},"page":"31-44","source":"Crossref","is-referenced-by-count":11,"title":["Randomized clinical trial: Combination antiretroviral therapy with tenofovir-emtricitabine and lopinavir-ritonavir in patients with primary biliary cholangitis"],"prefix":"10.3138","volume":"2","author":[{"given":"Ellina","family":"Lytvyak","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Alberta, Edmonton, Alberta;"},{"name":"Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, 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