Safety profile of maraviroc in patients coinfected with HIV-1 and hepatitis B or C included in the maraviroc expanded access program

Adriano Lazzarin, Soe Than, Srinivas R. Valluri, Jayvant Heera, Geoffrey Mukwaya

Research output: Contribution to journalArticle

Abstract

Objective: To evaluate the safety of maraviroc with other antiretrovirals in patients with HIV-1 coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV).Methods: This was a multicenter, noncomparative, open-label, expanded access program (EAP) initiated in February 2007. Patients with CCR5-tropic HIV-1 and HIV-1 RNA ≥1000 copies/mL on their current treatment received maraviroc 300 mg (150 mg with protease inhibitors) twice daily with optimized background therapy (OBT), which could include the newer agents raltegravir, etravirine, and darunavir. The adverse event (AE) profile was compared with the active and placebo arms of the maraviroc phase III clinical trials MOTIVATE 1 and 2, where the OBT did not include these agents.Results: A total of 1,032 patients were enrolled: 51 HIV/HBV coinfected; 149 HIV/HCV coinfected, 9 HIV/HBV/HCV coinfected, and 823 HIV-1 monoinfected. Most (76%) received at least 1 newer agent. Overall AE frequency was comparable across coinfection groups (63%-72%). Hepatobiliary events were more common in HIV/HCV coinfection than in HIV monoinfection or HIV/HBV coin-fection (10.0, 4.8, and 3.1 per 100 patient-years, respectively). Across all coinfection groups, there was a trend toward lower exposure-adjusted rates of serious and hepatobiliary AEs in the EAP than in the MOTIVATE studies. Grade 3/4 transaminase elevations in patients receiving maraviroc in the EAP and MOTIVATE were comparable with those seen in the MOTIVATE placebo arm. Conclusion: Maraviroc plus an OBT did not increase the incidence of AEs or severe laboratory liver abnormalities in HIV-1-infected patients coinfected with HBV or HCV.

Original languageEnglish
Pages (from-to)83-89
Number of pages7
JournalHIV Clinical Trials
Volume13
Issue number2
DOIs
Publication statusPublished - Jan 1 2012

Fingerprint

Hepatitis C
Hepatitis B
HIV-1
Hepatitis B virus
Hepacivirus
HIV
Safety
Coinfection
etravirine
Placebos
Phase III Clinical Trials
Numismatics
Therapeutics
Transaminases
Protease Inhibitors
maraviroc
RNA
Liver
Incidence

Keywords

  • CCR5 antagonists
  • coinfection
  • hepatitis B virus
  • hepatitis C virus
  • HIV
  • maraviroc

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Safety profile of maraviroc in patients coinfected with HIV-1 and hepatitis B or C included in the maraviroc expanded access program. / Lazzarin, Adriano; Than, Soe; Valluri, Srinivas R.; Heera, Jayvant; Mukwaya, Geoffrey.

In: HIV Clinical Trials, Vol. 13, No. 2, 01.01.2012, p. 83-89.

Research output: Contribution to journalArticle

Lazzarin, Adriano ; Than, Soe ; Valluri, Srinivas R. ; Heera, Jayvant ; Mukwaya, Geoffrey. / Safety profile of maraviroc in patients coinfected with HIV-1 and hepatitis B or C included in the maraviroc expanded access program. In: HIV Clinical Trials. 2012 ; Vol. 13, No. 2. pp. 83-89.
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abstract = "Objective: To evaluate the safety of maraviroc with other antiretrovirals in patients with HIV-1 coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV).Methods: This was a multicenter, noncomparative, open-label, expanded access program (EAP) initiated in February 2007. Patients with CCR5-tropic HIV-1 and HIV-1 RNA ≥1000 copies/mL on their current treatment received maraviroc 300 mg (150 mg with protease inhibitors) twice daily with optimized background therapy (OBT), which could include the newer agents raltegravir, etravirine, and darunavir. The adverse event (AE) profile was compared with the active and placebo arms of the maraviroc phase III clinical trials MOTIVATE 1 and 2, where the OBT did not include these agents.Results: A total of 1,032 patients were enrolled: 51 HIV/HBV coinfected; 149 HIV/HCV coinfected, 9 HIV/HBV/HCV coinfected, and 823 HIV-1 monoinfected. Most (76{\%}) received at least 1 newer agent. Overall AE frequency was comparable across coinfection groups (63{\%}-72{\%}). Hepatobiliary events were more common in HIV/HCV coinfection than in HIV monoinfection or HIV/HBV coin-fection (10.0, 4.8, and 3.1 per 100 patient-years, respectively). Across all coinfection groups, there was a trend toward lower exposure-adjusted rates of serious and hepatobiliary AEs in the EAP than in the MOTIVATE studies. Grade 3/4 transaminase elevations in patients receiving maraviroc in the EAP and MOTIVATE were comparable with those seen in the MOTIVATE placebo arm. Conclusion: Maraviroc plus an OBT did not increase the incidence of AEs or severe laboratory liver abnormalities in HIV-1-infected patients coinfected with HBV or HCV.",
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AU - Than, Soe

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AU - Heera, Jayvant

AU - Mukwaya, Geoffrey

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N2 - Objective: To evaluate the safety of maraviroc with other antiretrovirals in patients with HIV-1 coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV).Methods: This was a multicenter, noncomparative, open-label, expanded access program (EAP) initiated in February 2007. Patients with CCR5-tropic HIV-1 and HIV-1 RNA ≥1000 copies/mL on their current treatment received maraviroc 300 mg (150 mg with protease inhibitors) twice daily with optimized background therapy (OBT), which could include the newer agents raltegravir, etravirine, and darunavir. The adverse event (AE) profile was compared with the active and placebo arms of the maraviroc phase III clinical trials MOTIVATE 1 and 2, where the OBT did not include these agents.Results: A total of 1,032 patients were enrolled: 51 HIV/HBV coinfected; 149 HIV/HCV coinfected, 9 HIV/HBV/HCV coinfected, and 823 HIV-1 monoinfected. Most (76%) received at least 1 newer agent. Overall AE frequency was comparable across coinfection groups (63%-72%). Hepatobiliary events were more common in HIV/HCV coinfection than in HIV monoinfection or HIV/HBV coin-fection (10.0, 4.8, and 3.1 per 100 patient-years, respectively). Across all coinfection groups, there was a trend toward lower exposure-adjusted rates of serious and hepatobiliary AEs in the EAP than in the MOTIVATE studies. Grade 3/4 transaminase elevations in patients receiving maraviroc in the EAP and MOTIVATE were comparable with those seen in the MOTIVATE placebo arm. Conclusion: Maraviroc plus an OBT did not increase the incidence of AEs or severe laboratory liver abnormalities in HIV-1-infected patients coinfected with HBV or HCV.

AB - Objective: To evaluate the safety of maraviroc with other antiretrovirals in patients with HIV-1 coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV).Methods: This was a multicenter, noncomparative, open-label, expanded access program (EAP) initiated in February 2007. Patients with CCR5-tropic HIV-1 and HIV-1 RNA ≥1000 copies/mL on their current treatment received maraviroc 300 mg (150 mg with protease inhibitors) twice daily with optimized background therapy (OBT), which could include the newer agents raltegravir, etravirine, and darunavir. The adverse event (AE) profile was compared with the active and placebo arms of the maraviroc phase III clinical trials MOTIVATE 1 and 2, where the OBT did not include these agents.Results: A total of 1,032 patients were enrolled: 51 HIV/HBV coinfected; 149 HIV/HCV coinfected, 9 HIV/HBV/HCV coinfected, and 823 HIV-1 monoinfected. Most (76%) received at least 1 newer agent. Overall AE frequency was comparable across coinfection groups (63%-72%). Hepatobiliary events were more common in HIV/HCV coinfection than in HIV monoinfection or HIV/HBV coin-fection (10.0, 4.8, and 3.1 per 100 patient-years, respectively). Across all coinfection groups, there was a trend toward lower exposure-adjusted rates of serious and hepatobiliary AEs in the EAP than in the MOTIVATE studies. Grade 3/4 transaminase elevations in patients receiving maraviroc in the EAP and MOTIVATE were comparable with those seen in the MOTIVATE placebo arm. Conclusion: Maraviroc plus an OBT did not increase the incidence of AEs or severe laboratory liver abnormalities in HIV-1-infected patients coinfected with HBV or HCV.

KW - CCR5 antagonists

KW - coinfection

KW - hepatitis B virus

KW - hepatitis C virus

KW - HIV

KW - maraviroc

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