Hepatic safety in subjects with HIV-1 and hepatitis C and/or B virus: A randomized, double-blind study of maraviroc versus placebo in combination with antiretroviral agents

Juergen K. Rockstroh, Vicente Soriano, Frank Plonski, Meena Bansal, Gerd Fätkenheuer, Catherine B. Small, David Asmuth, Gilles Pialoux, Geoffrey Mukwaya, Shyla Jagannatha, Jayvant Heera, Juan A. Pineda

Research output: Contribution to journalArticle

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Abstract

Background: One of the more clinically relevant co-morbidities in HIV-infected patients is the development of progressive liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV). In addition, hepatotoxicity has been observed with prolonged use of antiretroviral agents. Objective: To evaluate the hepatic safety of maraviroc in combination with other antiretroviral agents in HIV-1-infected subjects co-infected with HCV and/or HBV. Methods: In this 148-week randomized, double-blind, placebo-controlled, multicentre study (NCT01327547), subjects received maraviroc twice daily (n=70) or placebo (n=67) in combination with other antiretroviral agents. Primary endpoint: the percentage at week 48 of subjects with Grade 3 and Grade 4 ALT abnormalities, defined as >5× upper limit of normal (ULN) if baseline ALT≤ULN or >3.5× baseline if baseline ALT>ULN in the maraviroc versus the placebo arm. Results: At week 48, one subject in each group had met the primary endpoint definition. No subjects met protocol-defined liver stopping criteria and there were no cases of Hy’s law or treatment-related hepatobiliary serious adverse events. No significant difference in change from baseline in enhanced liver fibrosis or hepatic elastography was observed between groups. Treatment-related hepatobiliary adverse events were reported in one and two subjects receiving maraviroc and placebo, respectively; discontinuations due to treatment-related AEs occurred in four and two subjects receiving maraviroc and placebo, respectively; two deaths were reported in the placebo group. Conclusions: The use of maraviroc does not increase hepatotoxicity in HIV-1-infected subjects co-infected with HCV and/or HBV through 48 weeks of treatment.

Original languageEnglish (US)
Pages (from-to)72-80
Number of pages9
JournalHIV Clinical Trials
Volume16
Issue number2
DOIs
StatePublished - 2015

Fingerprint

Anti-Retroviral Agents
Double-Blind Method
Hepatitis B virus
Hepacivirus
HIV-1
Placebos
Safety
Liver
Elasticity Imaging Techniques
Therapeutics
Liver Cirrhosis
Multicenter Studies
maraviroc
Liver Diseases
HIV
Morbidity

Keywords

  • Hepatitis B
  • Hepatitis C
  • Hepatotoxicity
  • HIV
  • Maraviroc

ASJC Scopus subject areas

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

Cite this

Hepatic safety in subjects with HIV-1 and hepatitis C and/or B virus : A randomized, double-blind study of maraviroc versus placebo in combination with antiretroviral agents. / Rockstroh, Juergen K.; Soriano, Vicente; Plonski, Frank; Bansal, Meena; Fätkenheuer, Gerd; Small, Catherine B.; Asmuth, David; Pialoux, Gilles; Mukwaya, Geoffrey; Jagannatha, Shyla; Heera, Jayvant; Pineda, Juan A.

In: HIV Clinical Trials, Vol. 16, No. 2, 2015, p. 72-80.

Research output: Contribution to journalArticle

Rockstroh, JK, Soriano, V, Plonski, F, Bansal, M, Fätkenheuer, G, Small, CB, Asmuth, D, Pialoux, G, Mukwaya, G, Jagannatha, S, Heera, J & Pineda, JA 2015, 'Hepatic safety in subjects with HIV-1 and hepatitis C and/or B virus: A randomized, double-blind study of maraviroc versus placebo in combination with antiretroviral agents', HIV Clinical Trials, vol. 16, no. 2, pp. 72-80. https://doi.org/10.1179/1528433614Z.0000000011
Rockstroh, Juergen K. ; Soriano, Vicente ; Plonski, Frank ; Bansal, Meena ; Fätkenheuer, Gerd ; Small, Catherine B. ; Asmuth, David ; Pialoux, Gilles ; Mukwaya, Geoffrey ; Jagannatha, Shyla ; Heera, Jayvant ; Pineda, Juan A. / Hepatic safety in subjects with HIV-1 and hepatitis C and/or B virus : A randomized, double-blind study of maraviroc versus placebo in combination with antiretroviral agents. In: HIV Clinical Trials. 2015 ; Vol. 16, No. 2. pp. 72-80.
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abstract = "Background: One of the more clinically relevant co-morbidities in HIV-infected patients is the development of progressive liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV). In addition, hepatotoxicity has been observed with prolonged use of antiretroviral agents. Objective: To evaluate the hepatic safety of maraviroc in combination with other antiretroviral agents in HIV-1-infected subjects co-infected with HCV and/or HBV. Methods: In this 148-week randomized, double-blind, placebo-controlled, multicentre study (NCT01327547), subjects received maraviroc twice daily (n=70) or placebo (n=67) in combination with other antiretroviral agents. Primary endpoint: the percentage at week 48 of subjects with Grade 3 and Grade 4 ALT abnormalities, defined as >5× upper limit of normal (ULN) if baseline ALT≤ULN or >3.5× baseline if baseline ALT>ULN in the maraviroc versus the placebo arm. Results: At week 48, one subject in each group had met the primary endpoint definition. No subjects met protocol-defined liver stopping criteria and there were no cases of Hy’s law or treatment-related hepatobiliary serious adverse events. No significant difference in change from baseline in enhanced liver fibrosis or hepatic elastography was observed between groups. Treatment-related hepatobiliary adverse events were reported in one and two subjects receiving maraviroc and placebo, respectively; discontinuations due to treatment-related AEs occurred in four and two subjects receiving maraviroc and placebo, respectively; two deaths were reported in the placebo group. Conclusions: The use of maraviroc does not increase hepatotoxicity in HIV-1-infected subjects co-infected with HCV and/or HBV through 48 weeks of treatment.",
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T2 - A randomized, double-blind study of maraviroc versus placebo in combination with antiretroviral agents

AU - Rockstroh, Juergen K.

AU - Soriano, Vicente

AU - Plonski, Frank

AU - Bansal, Meena

AU - Fätkenheuer, Gerd

AU - Small, Catherine B.

AU - Asmuth, David

AU - Pialoux, Gilles

AU - Mukwaya, Geoffrey

AU - Jagannatha, Shyla

AU - Heera, Jayvant

AU - Pineda, Juan A.

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N2 - Background: One of the more clinically relevant co-morbidities in HIV-infected patients is the development of progressive liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV). In addition, hepatotoxicity has been observed with prolonged use of antiretroviral agents. Objective: To evaluate the hepatic safety of maraviroc in combination with other antiretroviral agents in HIV-1-infected subjects co-infected with HCV and/or HBV. Methods: In this 148-week randomized, double-blind, placebo-controlled, multicentre study (NCT01327547), subjects received maraviroc twice daily (n=70) or placebo (n=67) in combination with other antiretroviral agents. Primary endpoint: the percentage at week 48 of subjects with Grade 3 and Grade 4 ALT abnormalities, defined as >5× upper limit of normal (ULN) if baseline ALT≤ULN or >3.5× baseline if baseline ALT>ULN in the maraviroc versus the placebo arm. Results: At week 48, one subject in each group had met the primary endpoint definition. No subjects met protocol-defined liver stopping criteria and there were no cases of Hy’s law or treatment-related hepatobiliary serious adverse events. No significant difference in change from baseline in enhanced liver fibrosis or hepatic elastography was observed between groups. Treatment-related hepatobiliary adverse events were reported in one and two subjects receiving maraviroc and placebo, respectively; discontinuations due to treatment-related AEs occurred in four and two subjects receiving maraviroc and placebo, respectively; two deaths were reported in the placebo group. Conclusions: The use of maraviroc does not increase hepatotoxicity in HIV-1-infected subjects co-infected with HCV and/or HBV through 48 weeks of treatment.

AB - Background: One of the more clinically relevant co-morbidities in HIV-infected patients is the development of progressive liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV). In addition, hepatotoxicity has been observed with prolonged use of antiretroviral agents. Objective: To evaluate the hepatic safety of maraviroc in combination with other antiretroviral agents in HIV-1-infected subjects co-infected with HCV and/or HBV. Methods: In this 148-week randomized, double-blind, placebo-controlled, multicentre study (NCT01327547), subjects received maraviroc twice daily (n=70) or placebo (n=67) in combination with other antiretroviral agents. Primary endpoint: the percentage at week 48 of subjects with Grade 3 and Grade 4 ALT abnormalities, defined as >5× upper limit of normal (ULN) if baseline ALT≤ULN or >3.5× baseline if baseline ALT>ULN in the maraviroc versus the placebo arm. Results: At week 48, one subject in each group had met the primary endpoint definition. No subjects met protocol-defined liver stopping criteria and there were no cases of Hy’s law or treatment-related hepatobiliary serious adverse events. No significant difference in change from baseline in enhanced liver fibrosis or hepatic elastography was observed between groups. Treatment-related hepatobiliary adverse events were reported in one and two subjects receiving maraviroc and placebo, respectively; discontinuations due to treatment-related AEs occurred in four and two subjects receiving maraviroc and placebo, respectively; two deaths were reported in the placebo group. Conclusions: The use of maraviroc does not increase hepatotoxicity in HIV-1-infected subjects co-infected with HCV and/or HBV through 48 weeks of treatment.

KW - Hepatitis B

KW - Hepatitis C

KW - Hepatotoxicity

KW - HIV

KW - Maraviroc

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