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

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

doi:10.1093/jac/dks130

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. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

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 / M. Nelson, G. Amaya, N. Clumeck, C. Arns da cunha, D. Jayaweera, P. Junod, T. Li, P. Tebas, M. Stevens, A. Buelens, S. Vanveggel, K. Boven, L. Abusamra, P. Cahn, H.E. Laplume, I. Cassetti, M. Ceriotto, M.D. Martins, A. Krolewiecki, 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, 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.-. 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.-. Hung, H.-. Lee, 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.-. 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.-. 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. Arasteh, S. Esser, G. Fatkenheuer, T. Lutz, R. Schmidt, D. Schuster, H.-. Stellbrink, N. Kumarasamy, P. Patil, A. Canton Martinez, A. Rodriguez-French, N. Sosa. - In: JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY. - ISSN 1460-2091. - 67:8(2012 Aug), pp. dks130.2020-dks130.2028.

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

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

2012

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. © The Author 2012. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.

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	Parole chiave
	
			Efavirenz; HBV; HCV; Hepatic safety; Hepatitis; Non-nucleoside reverse transcriptase inhibitors; TMC278; Adolescent; Adult; Aged; Alanine Transaminase; Animals; Antiviral Agents; Aspartate Aminotransferases; Benzoxazines; Coinfection; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; HIV Infections; HIV-1; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis C; Hepatitis C Antibodies; Humans; Liver; Liver Function Tests; Male; Middle Aged; Nitriles; Placebos; Pyrimidines; Rilpivirine; Treatment Outcome; Young Adult
		
	Settori scientifico-disciplinari dell'articolo
	
			Settore MED/17 - Malattie Infettive
		
	Data di pubblicazione
	
			ago-2012
		
	Rivista in ANCE
	
			JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
		
	DOI
	
			https://dx.doi.org/10.1093/jac/dks130
		
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			01 - Articolo su periodico

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