Efficacy and safety of rilpivirine in treatment-naive, HIV-1-infected patients with hepatitis B virus/hepatitis C virus coinfection enrolled in the phase III randomized, double-blind ECHO and THRIVE trials

Mark Nelson, Gerardo Amaya, Nathan Clumeck, Clovis Arns da cunha, Dushyantha Jayaweera, Patrice Junod, Taisheng Li, Pablo Tebas, Marita Stevens, Annemie Buelens, Simon Vanveggel, Katia Boven, L. Abusamra, P. Cahn, H. E. Laplume, I. Cassetti, M. Ceriotto, M. D. Martins, A. Krolewiecki, L. Amarilis LugoR. Bolan, L. Bush, R. Corales, L. Crane, J. De Vente, M. Fischl, J. Gathe, R. Greenberg, K. Henry, D. Jayaweera, P. Kumar, J. Lalezari, J. Leider, R. Lubelchek, C. Martorell, K. Mounzer, C. Cohen, H. Olivet, R. Ortiz, F. Rhame, A. Roberts, P. Ruane, A. Scribner, S. Segal-Maurer, W. Short, L. Sloan, T. Wilkin, M. Wohlfeiler, B. Yangco, M. Bloch, J. Gold, J. Hoy, P. Martinez, D. Baker, R. Finlayson, N. Roth, A. Rieger, N. Vetter, R. Zangerle, C. A. Da Cunha, B. Grinsztejn, J. V. Madruga, J. H. Pilotto, D. Sampaio, C. R. Gonsalez, M. P. Lima, F. Rangel, A. Timerman, P. Junod, D. Kilby, A. Rachlis, S. Walmsley, M. Boissonnault, J. Brunetta, J. De Wet, J. Gill, K. Kasper, J. Macleod, J. Gerstoft, L. Mathiesen, C. Pedersen, L. Cotte, P. M. Girard, J. M. Molina, F. Raffi, D. Vittecoq, Y. Yazdanpanah, P. Yeni, F. Boue, C. Katlama, J. Reynes, M. Fisher, M. Nelson, C. Orkin, S. Taylor, M. Johnson, E. Wilkins, I. G. Williams, A. Winston, A. Lazzarin, P. Narciso, A. Orani, S. Rusconi, A. Antinori, G. Carosi, F. Mazzotta, G. Amaya, G. Reyes-Teran, J. Andrade-Villanueva, J. G. Sierra Madero, B. Rijnders, J. Santana, C. Zorrilla, F. Antunes, T. Branco, R. Sarmento, E. Castro, T. Eugenio, K. Mansinho, R. Marques, D. Duiculescu, L. Negrutiu, L. Prisacariu, V. Kulagin, E. Voronin, A. Yakovlev, N. Dushkina, A. Pronin, O. Tsibakova, E. Vinogradova, E. Baraldi, N. David, O. Ebrahim, E. Krantz, G. H. Latiff, D. Spencer, R. Wood, M. Botes, F. Conradie, J. Fourie, L. Mohapi, D. Petit, D. Steyn, J. R. Arribas, J. Portilla Sogorb, E. Ribera, I. Santos Gil, B. Clotet, F. Gutierrez, D. Podzamczer, V. Soriano, K. Westling, P. Chetchotisakd, T. Sirisanthana, S. Sungkanuparph, A. Vibhagool, K. Ruxrungtham, W. Techasathit, C. C. Hung, H. C. Lee, H. H. Lin, W. W. Wong, H. Albrecht, N. Bellos, D. Berger, C. Brinson, B. Casanas, R. Elion, J. Feinberg, T. File, J. Flamm, C. Hicks, S. Hodder, C. B. Hsiao, P. Kadlecik, H. Khanlou, C. Kinder, R. Liporace, C. Mayer, D. Mildvan, A. Mills, R. A. Myers, I. Nadeem, O. Osiyemi, M. Para, G. Pierone, B. Rashbaum, J. Rodriguez, M. Saag, J. Sampson, R. Samuel, M. Sension, P. Shalit, P. Tebas, W. Towner, A. Wilkin, J. Eron, D. Wohl, R. Colebunders, N. Clumeck, J. C. Goffard, F. Van Wanzeele, E. Van Wijngaerden, J. Ballesteros, R. Northland, C. Perez, L. Hongzhou, T. Li, W. Cai, H. Wu, X. Li, G. Herrera, K. Arastéh, S. Esser, G. Fätkenheuer, T. Lutz, R. Schmidt, D. Schuster, H. J. Stellbrink, N. Kumarasamy, P. Patil, A. Canton Martinez, A. Rodriguez-French, N. Sosa

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Abstract

Objectives: The efficacy and hepatic safety of the non-nucleoside reverse transcriptase inhibitors rilpivirine (TMC278) and efavirenz were compared in treatment-naive, HIV-infected adults with concurrent hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection in the pooled week 48 analysis of the Phase III, double-blind, randomized ECHO (NCT00540449) and THRIVE (NCT00543725) trials. Methods: Patients received 25 mg of rilpivirine once daily or 600 mg of efavirenz once daily, plus two nucleoside/nucleotide reverse transcriptase inhibitors. At screening, patients had alanine aminotransferase/aspartate aminotransferase levels ≤5× the upper limit of normal. HBV and HCV status was determined at baseline by HBV surface antigen, HCV antibody and HCV RNA testing. Results: HBV/HCV coinfection status was known for 670 patients in the rilpivirine group and 665 in the efavirenz group. At baseline, 49 rilpivirine and 63 efavirenz patients [112/1335 (8.4%)] were coinfected with either HBV [55/1357 (4.1%)] or HCV [57/1333 (4.3%)]. The safety analysis included all available data, including beyond week 48. Eight patients seroconverted during the study (rilpivirine: five; efavirenz: three). A higher proportion of patients achieved viral load <50 copies/mL (intent to treat, time to loss of virological response) in the subgroup without HBV/HCV coinfection (rilpivirine: 85.0%; efavirenz: 82.6%) than in the coinfected subgroup (rilpivirine: 73.5%; efavirenz: 79.4%) (rilpivirine, P = 0.04 and efavirenz, P = 0.49, Fisher's exact test). The incidence of hepatic adverse events (AEs) was low in both groups in the overall population (rilpivirine: 5.5% versus efavirenz: 6.6%) and was higher in HBV/HCV-coinfected patients than in those not coinfected (26.7% versus 4.1%, respectively). Conclusions: Hepatic AEs were more common and response rates lower in HBV/HCV-coinfected patients treated with rilpivirine or efavirenz than in those who were not coinfected.

Original languageEnglish (US)
Article numberdks130
Pages (from-to)2020-2028
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume67
Issue number8
DOIs
StatePublished - Aug 2012

Bibliographical note

Funding Information:
This study was sponsored by Janssen Pharmaceuticals. The medical writing support and assistance in coordinating and collating author contributions from Ian Woolveridge (principal writer) of Gardiner-Caldwell Communications was funded by Janssen.

Funding Information:
M. N. has acted as consultant and received educational and research grants from Merck Sharpe & Dohme (MSD), GlaxoSmithKline (GSK), Bristol-Myers Squibb (BMS), Gilead Sciences, Johnson & Johnson, Janssen, Abbott Laboratories, Boehringer Ingelheim (BI), Schering-Plough, Pfizer and Roche. N. C. has participated as an expert or investigator for Abbott Laboratories, BI, Gilead Sciences, GSK, MSD, Pfizer, Roche and Janssen. C. A. da C. has received research support from BMS, Janssen, Gilead Sciences and Schering-Plough. In addition, he has served as consultant and speaker for BMS, Janssen-Cilag, Gilead Sciences, Abbott Laboratories, MSD and Roche. D. J. has been an investigator and/ or scientific advisor (Review Panel or Advisory Committee) for Janssen, BMS, Gilead Sciences, BI and GSK. He has received research support from Janssen, BMS, Roche and GSK, and speaker honorarium from Janssen, BMS, Gilead Sciences, BI, Roche and GSK. He has served as a consultant for Janssen, BMS, Gilead Sciences, Roche and GSK, and has been on the Speaker’s Bureau for Janssen, BMS, Gilead Sciences, BI and GSK. P. J. has received consulting fees and or grants from Abbott Laboratories, Gilead Sciences, Merck, Janssen, ViiV Healthcare and BMS. P. T. has received consulting fees from GSK, Merck and, more than 1 year since publication, Pfizer and Janssen. M. S., S. V. and K. B. are full-time

Keywords

  • Efavirenz
  • HBV
  • HCV
  • Hepatic safety
  • Hepatitis
  • Non-nucleoside reverse transcriptase inhibitors
  • TMC278

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