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 × 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 < 0.05) and in HBRV proviral load (P < 0.05) after 6 months of combination antiretroviral therapy. The majority of patients had diminished levels of LPRr after 6 months' 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.
RCT Entities:
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 × 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 < 0.05) and in HBRV proviral load (P < 0.05) after 6 months of combination antiretroviral therapy. The majority of patients had diminished levels of LPRr after 6 months' 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.
Entities:
Keywords:
combination antiretroviral therapy; human betaretrovirus; primary biliary cholangitis
Authors: Marina G Silveira; Elizabeth M Brunt; Jenny Heathcote; Gregory J Gores; Keith D Lindor; Marlyn J Mayo Journal: Hepatology Date: 2010-07 Impact factor: 17.425
Authors: F J Palella; K M Delaney; A C Moorman; M O Loveless; J Fuhrer; G A Satten; D J Aschman; S D Holmberg Journal: N Engl J Med Date: 1998-03-26 Impact factor: 91.245
Authors: Sharon Walmsley; Anchalee Avihingsanon; Jihad Slim; Douglas J Ward; Kiat Ruxrungtham; Jason Brunetta; U Fritz Bredeek; Dushyantha Jayaweera; Carol Jean Guittari; Peter Larson; Malte Schutz; François Raffi Journal: J Acquir Immune Defic Syndr Date: 2009-04-01 Impact factor: 3.731
Authors: A L Mason; K D Lindor; B R Bacon; C Vincent; J M Neuberger; S T Wasilenko Journal: Aliment Pharmacol Ther Date: 2008-10-01 Impact factor: 8.171
Authors: Gwenda Verweel; David M Burger; Nancy L Sheehan; Alina S Bergshoeff; Adilia Warris; Linda C van der Knaap; Gertjan Driessen; Ronald de Groot; Nico G Hartwig Journal: Antivir Ther Date: 2007
Authors: Harpreet Johal; Gillian Marie Scott; Robert Jones; Catherine Camaris; Stephen Riordan; William D Rawlinson Journal: J Hepatol Date: 2008-12-26 Impact factor: 25.083
Authors: Aldo J Montano-Loza; Jessica R Allegretti; Angela Cheung; Maryam Ebadi; David Jones; Nanda Kerkar; Cynthia Levy; Sumera Rizvi; John M Vierling; Fernando Alvarez; Wayne Bai; Susan Gilmour; Aliya Gulamhusein; Orlee Guttman; Bettina E Hansen; Sonya MacParland; Andrew Mason; Fernanda Onofrio; Pere Santamaria; Ashley Stueck; Mark Swain; Catherine Vincent; Amanda Ricciuto; Gideon Hirschfield Journal: Can Liver J Date: 2021-11-11