Hepatic safety of maraviroc in patients with HIV-1 and hepatitis C and/or B virus: 144-week results from a randomized, placebo-controlled trial

Juergen K. Rockstroh, Frank Plonski, Meena Bansal, Gerd Fätkenheuer, Catherine B. Small, David Asmuth, Gilles Pialoux, Rebecca Zhang-Roper, Ronnie Wang, Juan A. Pineda, Jayvant Heera

Research output: Contribution to journalArticle

3 Citations (Scopus)

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, placebocontrolled, 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 treatmentrelated 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.

Original languageEnglish (US)
Pages (from-to)263-269
Number of pages7
JournalAntiviral Therapy
Volume22
Issue number3
DOIs
StatePublished - 2017

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Hepatitis B virus
Hepacivirus
HIV-1
Randomized Controlled Trials
Placebos
Safety
Liver
Elasticity Imaging Techniques
Liver Cirrhosis
Alanine Transaminase
maraviroc
Biopsy
Therapeutics
Multicenter Studies
Fibrosis

ASJC Scopus subject areas

  • Medicine(all)
  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Hepatic safety of maraviroc in patients with HIV-1 and hepatitis C and/or B virus : 144-week results from a randomized, placebo-controlled trial. / Rockstroh, Juergen K.; Plonski, Frank; Bansal, Meena; Fätkenheuer, Gerd; Small, Catherine B.; Asmuth, David; Pialoux, Gilles; Zhang-Roper, Rebecca; Wang, Ronnie; Pineda, Juan A.; Heera, Jayvant.

In: Antiviral Therapy, Vol. 22, No. 3, 2017, p. 263-269.

Research output: Contribution to journalArticle

Rockstroh, JK, Plonski, F, Bansal, M, Fätkenheuer, G, Small, CB, Asmuth, D, Pialoux, G, Zhang-Roper, R, Wang, R, Pineda, JA & Heera, J 2017, 'Hepatic safety of maraviroc in patients with HIV-1 and hepatitis C and/or B virus: 144-week results from a randomized, placebo-controlled trial', Antiviral Therapy, vol. 22, no. 3, pp. 263-269. https://doi.org/10.3851/IMP3116
Rockstroh, Juergen K. ; Plonski, Frank ; Bansal, Meena ; Fätkenheuer, Gerd ; Small, Catherine B. ; Asmuth, David ; Pialoux, Gilles ; Zhang-Roper, Rebecca ; Wang, Ronnie ; Pineda, Juan A. ; Heera, Jayvant. / Hepatic safety of maraviroc in patients with HIV-1 and hepatitis C and/or B virus : 144-week results from a randomized, placebo-controlled trial. In: Antiviral Therapy. 2017 ; Vol. 22, No. 3. pp. 263-269.
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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, placebocontrolled, 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 treatmentrelated 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.",
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T2 - 144-week results from a randomized, placebo-controlled trial

AU - Rockstroh, Juergen K.

AU - Plonski, Frank

AU - Bansal, Meena

AU - Fätkenheuer, Gerd

AU - Small, Catherine B.

AU - Asmuth, David

AU - Pialoux, Gilles

AU - Zhang-Roper, Rebecca

AU - Wang, Ronnie

AU - Pineda, Juan A.

AU - Heera, Jayvant

PY - 2017

Y1 - 2017

N2 - 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, placebocontrolled, 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 treatmentrelated 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.

AB - 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, placebocontrolled, 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 treatmentrelated 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.

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