Juergen K Rockstroh1, Frank Plonski2, Meena Bansal3, Gerd Fätkenheuer4, Catherine B Small5,6, David M Asmuth7, Gilles Pialoux8, Rebecca Zhang-Roper9, Ronnie Wang10, Juan A Pineda11, Jayvant Heera10. 1. Department of Medicine I, University of Bonn, Bonn, Germany. 2. Global Clinical Development, Pfizer Inc., Collegeville, PA, USA. 3. Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4. Department I of Internal Medicine, University Hospital Cologne, Cologne, Germany. 5. Department of Medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York, NY, USA. 6. Department of Medicine, Division of Infectious Diseases, New York Medical College, Valhalla, NY, USA. 7. Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA, USA. 8. Maladies Infectieuses et Tropicales, Hôpital Tenon, Paris, France. 9. Safety Evaluation and Risk Management, GlaxoSmithKline, London, UK. 10. Clinical Sciences, Pfizer Inc., Groton, CT, USA. 11. Unit of Infectious Diseases, Hospital Universitario de Valme, Instituto de Investigación Biomédica de Sevilla (IBIS), Seville, Spain.
Abstract
BACKGROUND: In the primary 48-week analysis of a hepatic safety trial in patients with HIV-1 coinfected with HBV and/or HCV, maraviroc-containing treatment regimens were not associated with increased hepatotoxicity. METHODS: In this randomized, double-blind, placebo-controlled, multicentre study, patients received maraviroc twice daily (n=70) or placebo (n=67) with concomitant antiretroviral therapy for 144 weeks (Clinicaltrials.gov identifier, NCT01327547). The primary end point was the proportion of patients with protocol-defined Grade 3/4 alanine aminotransferase (ALT) abnormalities through week 48. Key secondary end points included 144-week analysis of Grade 3/4 ALT abnormalities and liver fibrosis by enhanced liver fibrosis (ELF) testing, hepatic elastography and an optional biopsy substudy. RESULTS: Through 144 weeks of treatment, two (maraviroc) and three (placebo) patients met the protocol-defined Grade 3/4 ALT end point. Similar to the 48-week results, there were no statistically significant differences between groups in change from baseline in ELF or hepatic elastography. However, decreased elastography scores were noted in the maraviroc group. Blinded pathologist review suggested that 2 of 11 paired biopsies (both on maraviroc) showed signs of decreased fibrosis. One (maraviroc) and two (placebo) patients experienced treatment-related hepatobiliary adverse events (AEs). Five patients in the maraviroc group discontinued because of treatment-related AEs versus three in the placebo group. One death in the maraviroc group and two deaths in the placebo group were reported. CONCLUSIONS: Use of maraviroc did not increase hepatotoxicity in this population through 144 weeks. Further investigation regarding possible beneficial effects of maraviroc on liver fibrosis may be warranted.
RCT Entities:
BACKGROUND: In the primary 48-week analysis of a hepatic safety trial in patients with HIV-1 coinfected with HBV and/or HCV, maraviroc-containing treatment regimens were not associated with increased hepatotoxicity. METHODS: In this randomized, double-blind, placebo-controlled, multicentre study, patients received maraviroc twice daily (n=70) or placebo (n=67) with concomitant antiretroviral therapy for 144 weeks (Clinicaltrials.gov identifier, NCT01327547). The primary end point was the proportion of patients with protocol-defined Grade 3/4 alanine aminotransferase (ALT) abnormalities through week 48. Key secondary end points included 144-week analysis of Grade 3/4 ALT abnormalities and liver fibrosis by enhanced liver fibrosis (ELF) testing, hepatic elastography and an optional biopsy substudy. RESULTS: Through 144 weeks of treatment, two (maraviroc) and three (placebo) patients met the protocol-defined Grade 3/4 ALT end point. Similar to the 48-week results, there were no statistically significant differences between groups in change from baseline in ELF or hepatic elastography. However, decreased elastography scores were noted in the maraviroc group. Blinded pathologist review suggested that 2 of 11 paired biopsies (both on maraviroc) showed signs of decreased fibrosis. One (maraviroc) and two (placebo) patients experienced treatment-related hepatobiliary adverse events (AEs). Five patients in the maraviroc group discontinued because of treatment-related AEs versus three in the placebo group. One death in the maraviroc group and two deaths in the placebo group were reported. CONCLUSIONS: Use of maraviroc did not increase hepatotoxicity in this population through 144 weeks. Further investigation regarding possible beneficial effects of maraviroc on liver fibrosis may be warranted.
Authors: Jason T Blackard; Ling Kong; Susan D Rouster; Rebekah Karns; Paul S Horn; Shyam Kottilil; M Tarek Shata; Kenneth E Sherman Journal: PLoS One Date: 2019-10-29 Impact factor: 3.240
Authors: Barnaby Flower; Leanne McCabe; Chau Le Ngoc; Hung Le Manh; Phuong Le Thanh; Thuan Dang Trong; Thu Vo Thi; Hang Vu Thi Kim; Thanh Nguyen Tat; Dao Phan Thi Hong; An Nguyen Thi Chau; Tan Dinh Thi; Nga Tran Thi Tuyet; Joel Tarning; Cherry Kingsley; Evelyne Kestelyn; Sarah L Pett; Guy Thwaites; Vinh Chau Nguyen Van; David Smith; Eleanor Barnes; M Azim Ansari; Hugo Turner; Motiur Rahman; Ann Sarah Walker; Jeremy Day; Graham S Cooke Journal: Open Forum Infect Dis Date: 2021-06-09 Impact factor: 3.835