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

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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
Article numberdks130
Pages (from-to)2020-2028
Number of pages9
JournalJournal of Antimicrobial Chemotherapy
Volume67
Issue number8
DOIs
Publication statusPublished - Aug 2012

Keywords

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

Cite this

Nelson, Mark ; Amaya, Gerardo ; Clumeck, Nathan ; Arns da cunha, Clovis ; Jayaweera, Dushyantha ; Junod, Patrice ; Li, Taisheng ; Tebas, Pablo ; Stevens, Marita ; Buelens, Annemie ; Vanveggel, Simon ; Boven, Katia ; ECHO and THRIVE Study Groups. / 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. In: Journal of Antimicrobial Chemotherapy. 2012 ; Vol. 67, No. 8. pp. 2020-2028.
@article{def0f3dd912047c89acd9fff1e7f6e75,
title = "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",
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.",
keywords = "Efavirenz, HBV, HCV, Hepatic safety, Hepatitis, Non-nucleoside reverse transcriptase inhibitors, TMC278",
author = "Mark Nelson and Gerardo Amaya and Nathan Clumeck and {Arns da cunha}, Clovis and Dushyantha Jayaweera and Patrice Junod and Taisheng Li and Pablo Tebas and Marita Stevens and Annemie Buelens and Simon Vanveggel and Katia Boven and {ECHO and THRIVE Study Groups} and J. Hoy",
year = "2012",
month = "8",
doi = "10.1093/jac/dks130",
language = "English",
volume = "67",
pages = "2020--2028",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",
number = "8",

}

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 & ECHO and THRIVE Study Groups 2012, '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', Journal of Antimicrobial Chemotherapy, vol. 67, no. 8, dks130, pp. 2020-2028. https://doi.org/10.1093/jac/dks130

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, Mark; Amaya, Gerardo; Clumeck, Nathan; Arns da cunha, Clovis; Jayaweera, Dushyantha; Junod, Patrice; Li, Taisheng; Tebas, Pablo; Stevens, Marita; Buelens, Annemie; Vanveggel, Simon; Boven, Katia; ECHO and THRIVE Study Groups.

In: Journal of Antimicrobial Chemotherapy, Vol. 67, No. 8, dks130, 08.2012, p. 2020-2028.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - 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

AU - Nelson, Mark

AU - Amaya, Gerardo

AU - Clumeck, Nathan

AU - Arns da cunha, Clovis

AU - Jayaweera, Dushyantha

AU - Junod, Patrice

AU - Li, Taisheng

AU - Tebas, Pablo

AU - Stevens, Marita

AU - Buelens, Annemie

AU - Vanveggel, Simon

AU - Boven, Katia

AU - ECHO and THRIVE Study Groups

AU - Hoy, J.

PY - 2012/8

Y1 - 2012/8

N2 - 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.

AB - 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.

KW - Efavirenz

KW - HBV

KW - HCV

KW - Hepatic safety

KW - Hepatitis

KW - Non-nucleoside reverse transcriptase inhibitors

KW - TMC278

UR - http://www.scopus.com/inward/record.url?scp=84864505008&partnerID=8YFLogxK

U2 - 10.1093/jac/dks130

DO - 10.1093/jac/dks130

M3 - Article

VL - 67

SP - 2020

EP - 2028

JO - Journal of Antimicrobial Chemotherapy

JF - Journal of Antimicrobial Chemotherapy

SN - 0305-7453

IS - 8

M1 - dks130

ER -