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, ECHO and THRIVE Study Groups, L Abusamra, P Cahn, H E Laplume, I Cassetti, M Ceriotto, M D Martins, A Krolewiecki, M Bloch, J Gold, J Hoy, P Martinez, A Rieger, N Vetter, R Zangerle, C A Da Cunha, B Grinsztejn, J V Madruga, J H Pilotto, D Sampaio, P Junod, D Kilby, A Rachlis, S Walmsley, J Gerstoft, L Mathiesen, C Pedersen, L Cotte, P M Girard, J M Molina, F Raffi, D Vittecoq, Y Yazdanpanah, P Yeni, M Fisher, M Nelson, C Orkin, S Taylor, A Lazzarin, P Narciso, A Orani, S Rusconi, G Amaya, G Reyes-Teran, B Rijnders, J Santana, F Antunes, T Branco, R Sarmento, E Castro, T Eugenio, K Mansinho, D Duiculescu, L Negrutiu, L Prisacariu, V Kulagin, E Voronin, A Yakovlev, E Baraldi, N David, O Ebrahim, E Krantz, G H Latiff, D Spencer, R Wood, J R Arribas, J Portilla Sogorb, E Ribera, I Santos Gil, K Westling, P Chetchotisakd, T Sirisanthana, S Sungkanuparph, A Vibhagool, 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, D Baker, R Finlayson, N Roth, R Colebunders, N Clumeck, J-C Goffard, F Van Wanzeele, E Van Wijngaerden, C R Gonsalez, M P Lima, F Rangel, A Timerman, M Boissonnault, J Brunetta, J De Wet, J Gill, K Kasper, J Macleod, J Ballesteros, R Northland, C Perez, L Hongzhou, T Li, W Cai, H Wu, X Li, G Herrera, F Boue, C Katlama, J Reynes, K Arastéh, S Esser, G Fätkenheuer, T Lutz, R Schmidt, D Schuster, H-J Stellbrink, M Johnson, E Wilkins, I G Williams, A Winston, N Kumarasamy, P Patil, A Antinori, G Carosi, F Mazzotta, J Andrade-Villanueva, J G Sierra Madero, A Canton Martinez, A Rodriguez-French, N Sosa, R Marques, C Zorrilla, N Dushkina, A Pronin, O Tsibakova, E Vinogradova, M Botes, F Conradie, J Fourie, L Mohapi, D Petit, D Steyn, B Clotet, F Gutierrez, D Podzamczer, V Soriano, K Ruxrungtham, W Techasathit, L Amarilis Lugo, R 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, 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, ECHO and THRIVE Study Groups, L Abusamra, P Cahn, H E Laplume, I Cassetti, M Ceriotto, M D Martins, A Krolewiecki, M Bloch, J Gold, J Hoy, P Martinez, A Rieger, N Vetter, R Zangerle, C A Da Cunha, B Grinsztejn, J V Madruga, J H Pilotto, D Sampaio, P Junod, D Kilby, A Rachlis, S Walmsley, J Gerstoft, L Mathiesen, C Pedersen, L Cotte, P M Girard, J M Molina, F Raffi, D Vittecoq, Y Yazdanpanah, P Yeni, M Fisher, M Nelson, C Orkin, S Taylor, A Lazzarin, P Narciso, A Orani, S Rusconi, G Amaya, G Reyes-Teran, B Rijnders, J Santana, F Antunes, T Branco, R Sarmento, E Castro, T Eugenio, K Mansinho, D Duiculescu, L Negrutiu, L Prisacariu, V Kulagin, E Voronin, A Yakovlev, E Baraldi, N David, O Ebrahim, E Krantz, G H Latiff, D Spencer, R Wood, J R Arribas, J Portilla Sogorb, E Ribera, I Santos Gil, K Westling, P Chetchotisakd, T Sirisanthana, S Sungkanuparph, A Vibhagool, 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, D Baker, R Finlayson, N Roth, R Colebunders, N Clumeck, J-C Goffard, F Van Wanzeele, E Van Wijngaerden, C R Gonsalez, M P Lima, F Rangel, A Timerman, M Boissonnault, J Brunetta, J De Wet, J Gill, K Kasper, J Macleod, J Ballesteros, R Northland, C Perez, L Hongzhou, T Li, W Cai, H Wu, X Li, G Herrera, F Boue, C Katlama, J Reynes, K Arastéh, S Esser, G Fätkenheuer, T Lutz, R Schmidt, D Schuster, H-J Stellbrink, M Johnson, E Wilkins, I G Williams, A Winston, N Kumarasamy, P Patil, A Antinori, G Carosi, F Mazzotta, J Andrade-Villanueva, J G Sierra Madero, A Canton Martinez, A Rodriguez-French, N Sosa, R Marques, C Zorrilla, N Dushkina, A Pronin, O Tsibakova, E Vinogradova, M Botes, F Conradie, J Fourie, L Mohapi, D Petit, D Steyn, B Clotet, F Gutierrez, D Podzamczer, V Soriano, K Ruxrungtham, W Techasathit, L Amarilis Lugo, R 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
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.
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Source: PubMed