Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection

Mark Sulkowski, Susanna Naggie, Jacob Lalezari, Walford Jeffrey Fessel, Karam Mounzer, Margaret Shuhart, Anne F. Luetkemeyer, David Asmuth, Anuj Gaggar, Liyun Ni, Evguenia Svarovskaia, Diana M. Brainard, William T. Symonds, G. Mani Subramanian, John G. McHutchison, Maribel Rodriguez-Torres, Douglas Dieterich

Research output: Contribution to journalArticle

Abstract

IMPORTANCE: Treatment of hepatitis C virus (HCV) infection in patients also infected with human immunodeficiency virus (HIV) has been limited due to drug interactions with antiretroviral therapies (ARTs) and the need to use interferon. OBJECTIVE: To determine the rates of HCV eradication (sustained virologic response [SVR]) and adverse events in patients with HCV-HIV coinfection receiving sofosbuvir and ribavirin treatment. DESIGN, SETTING, AND PARTICIPANTS: Open-label, nonrandomized, uncontrolled phase 3 trial conducted at 34 treatment centers in the United States and Puerto Rico (August 2012-November 2013) evaluating treatment with sofosbuvir and ribavirin among patients with HCV genotypes 1, 2, or 3 and concurrent HIV. Patients were required to be receiving ART with HIV RNA values of 50 copies/mL or less and a CD4 T-cell count of more than 200 cells/μL or to have untreated HIV infection with a CD4 T-cell count of more than 500 cells/μL. Of the treatment-naive patients, 114 had HCV genotype 1 and 68 had HCV genotype 2 or 3, and 41 treatment experienced participants who had been treated with peginterferon-ribavirin had HCV genotype 2 or 3, for a total of 223 participants. INTERVENTIONS: Treatment-naive patients with HCV genotype 2 or 3 received 400 mg of sofosbuvir and weight-based ribavirin for 12 weeks and treatment-naive patients with HCV genotype 1 and treatment-experienced patients with HCV genotype 2 or 3 received the same treatment for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary study outcomewas the proportion of patients with SVR (serum HCV 12) after cessation of HCV therapy. RESULTS: Among treatment-naive participants, 87 patients (76%) of 114 (95%CI, 67%-84%) with genotype 1, 23 patients (88%) of 26 with genotype 2 (95%CI, 70%-985), and 28 patients (67%) of 42 with genotype 3 (95%CI, 51%-80%) achieved SVR12. Among treatment-experienced participants, 22 patients (92%) of 24 with genotype 2 (95%CI, 73%-99%) and 16 patients (94%) of 17 (95%CI, 71%-100%) achieved SVR12. The most common adverse events were fatigue, insomnia, headache, and nausea. Seven patients (3%) discontinued HCV treatment due to adverse events. No adverse effect on HIV disease or its treatment was observed. CONCLUSIONS AND RELEVANCE: In this open-label, nonrandomized, uncontrolled study, patients with HIV who were coinfected with HCV genotype 1, 2, or 3 who received the oral, interferon-free combination of sofosbuvir and ribavirin for 12 or 24 weeks had high rates of SVR12. Further studies of this oral regimen in diverse populations of coinfected patients are warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01667731.

Original languageEnglish (US)
Pages (from-to)353-361
Number of pages9
JournalJournal of the American Medical Association
Volume312
Issue number4
DOIs
StatePublished - 2014

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Ribavirin
Hepatitis C
Coinfection
Hepacivirus
HIV
Genotype
Therapeutics
Virus Diseases
Sofosbuvir
CD4 Lymphocyte Count
Interferons
T-Lymphocytes
Puerto Rico
Sleep Initiation and Maintenance Disorders
Drug Interactions

ASJC Scopus subject areas

  • Medicine(all)

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Sulkowski, M., Naggie, S., Lalezari, J., Fessel, W. J., Mounzer, K., Shuhart, M., ... Dieterich, D. (2014). Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. Journal of the American Medical Association, 312(4), 353-361. https://doi.org/10.1001/jama.2014.7734

Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. / Sulkowski, Mark; Naggie, Susanna; Lalezari, Jacob; Fessel, Walford Jeffrey; Mounzer, Karam; Shuhart, Margaret; Luetkemeyer, Anne F.; Asmuth, David; Gaggar, Anuj; Ni, Liyun; Svarovskaia, Evguenia; Brainard, Diana M.; Symonds, William T.; Subramanian, G. Mani; McHutchison, John G.; Rodriguez-Torres, Maribel; Dieterich, Douglas.

In: Journal of the American Medical Association, Vol. 312, No. 4, 2014, p. 353-361.

Research output: Contribution to journalArticle

Sulkowski, M, Naggie, S, Lalezari, J, Fessel, WJ, Mounzer, K, Shuhart, M, Luetkemeyer, AF, Asmuth, D, Gaggar, A, Ni, L, Svarovskaia, E, Brainard, DM, Symonds, WT, Subramanian, GM, McHutchison, JG, Rodriguez-Torres, M & Dieterich, D 2014, 'Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection', Journal of the American Medical Association, vol. 312, no. 4, pp. 353-361. https://doi.org/10.1001/jama.2014.7734
Sulkowski, Mark ; Naggie, Susanna ; Lalezari, Jacob ; Fessel, Walford Jeffrey ; Mounzer, Karam ; Shuhart, Margaret ; Luetkemeyer, Anne F. ; Asmuth, David ; Gaggar, Anuj ; Ni, Liyun ; Svarovskaia, Evguenia ; Brainard, Diana M. ; Symonds, William T. ; Subramanian, G. Mani ; McHutchison, John G. ; Rodriguez-Torres, Maribel ; Dieterich, Douglas. / Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection. In: Journal of the American Medical Association. 2014 ; Vol. 312, No. 4. pp. 353-361.
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T1 - Sofosbuvir and ribavirin for hepatitis C in patients with HIV coinfection

AU - Sulkowski, Mark

AU - Naggie, Susanna

AU - Lalezari, Jacob

AU - Fessel, Walford Jeffrey

AU - Mounzer, Karam

AU - Shuhart, Margaret

AU - Luetkemeyer, Anne F.

AU - Asmuth, David

AU - Gaggar, Anuj

AU - Ni, Liyun

AU - Svarovskaia, Evguenia

AU - Brainard, Diana M.

AU - Symonds, William T.

AU - Subramanian, G. Mani

AU - McHutchison, John G.

AU - Rodriguez-Torres, Maribel

AU - Dieterich, Douglas

PY - 2014

Y1 - 2014

N2 - IMPORTANCE: Treatment of hepatitis C virus (HCV) infection in patients also infected with human immunodeficiency virus (HIV) has been limited due to drug interactions with antiretroviral therapies (ARTs) and the need to use interferon. OBJECTIVE: To determine the rates of HCV eradication (sustained virologic response [SVR]) and adverse events in patients with HCV-HIV coinfection receiving sofosbuvir and ribavirin treatment. DESIGN, SETTING, AND PARTICIPANTS: Open-label, nonrandomized, uncontrolled phase 3 trial conducted at 34 treatment centers in the United States and Puerto Rico (August 2012-November 2013) evaluating treatment with sofosbuvir and ribavirin among patients with HCV genotypes 1, 2, or 3 and concurrent HIV. Patients were required to be receiving ART with HIV RNA values of 50 copies/mL or less and a CD4 T-cell count of more than 200 cells/μL or to have untreated HIV infection with a CD4 T-cell count of more than 500 cells/μL. Of the treatment-naive patients, 114 had HCV genotype 1 and 68 had HCV genotype 2 or 3, and 41 treatment experienced participants who had been treated with peginterferon-ribavirin had HCV genotype 2 or 3, for a total of 223 participants. INTERVENTIONS: Treatment-naive patients with HCV genotype 2 or 3 received 400 mg of sofosbuvir and weight-based ribavirin for 12 weeks and treatment-naive patients with HCV genotype 1 and treatment-experienced patients with HCV genotype 2 or 3 received the same treatment for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary study outcomewas the proportion of patients with SVR (serum HCV 12) after cessation of HCV therapy. RESULTS: Among treatment-naive participants, 87 patients (76%) of 114 (95%CI, 67%-84%) with genotype 1, 23 patients (88%) of 26 with genotype 2 (95%CI, 70%-985), and 28 patients (67%) of 42 with genotype 3 (95%CI, 51%-80%) achieved SVR12. Among treatment-experienced participants, 22 patients (92%) of 24 with genotype 2 (95%CI, 73%-99%) and 16 patients (94%) of 17 (95%CI, 71%-100%) achieved SVR12. The most common adverse events were fatigue, insomnia, headache, and nausea. Seven patients (3%) discontinued HCV treatment due to adverse events. No adverse effect on HIV disease or its treatment was observed. CONCLUSIONS AND RELEVANCE: In this open-label, nonrandomized, uncontrolled study, patients with HIV who were coinfected with HCV genotype 1, 2, or 3 who received the oral, interferon-free combination of sofosbuvir and ribavirin for 12 or 24 weeks had high rates of SVR12. Further studies of this oral regimen in diverse populations of coinfected patients are warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01667731.

AB - IMPORTANCE: Treatment of hepatitis C virus (HCV) infection in patients also infected with human immunodeficiency virus (HIV) has been limited due to drug interactions with antiretroviral therapies (ARTs) and the need to use interferon. OBJECTIVE: To determine the rates of HCV eradication (sustained virologic response [SVR]) and adverse events in patients with HCV-HIV coinfection receiving sofosbuvir and ribavirin treatment. DESIGN, SETTING, AND PARTICIPANTS: Open-label, nonrandomized, uncontrolled phase 3 trial conducted at 34 treatment centers in the United States and Puerto Rico (August 2012-November 2013) evaluating treatment with sofosbuvir and ribavirin among patients with HCV genotypes 1, 2, or 3 and concurrent HIV. Patients were required to be receiving ART with HIV RNA values of 50 copies/mL or less and a CD4 T-cell count of more than 200 cells/μL or to have untreated HIV infection with a CD4 T-cell count of more than 500 cells/μL. Of the treatment-naive patients, 114 had HCV genotype 1 and 68 had HCV genotype 2 or 3, and 41 treatment experienced participants who had been treated with peginterferon-ribavirin had HCV genotype 2 or 3, for a total of 223 participants. INTERVENTIONS: Treatment-naive patients with HCV genotype 2 or 3 received 400 mg of sofosbuvir and weight-based ribavirin for 12 weeks and treatment-naive patients with HCV genotype 1 and treatment-experienced patients with HCV genotype 2 or 3 received the same treatment for 24 weeks. MAIN OUTCOMES AND MEASURES: The primary study outcomewas the proportion of patients with SVR (serum HCV 12) after cessation of HCV therapy. RESULTS: Among treatment-naive participants, 87 patients (76%) of 114 (95%CI, 67%-84%) with genotype 1, 23 patients (88%) of 26 with genotype 2 (95%CI, 70%-985), and 28 patients (67%) of 42 with genotype 3 (95%CI, 51%-80%) achieved SVR12. Among treatment-experienced participants, 22 patients (92%) of 24 with genotype 2 (95%CI, 73%-99%) and 16 patients (94%) of 17 (95%CI, 71%-100%) achieved SVR12. The most common adverse events were fatigue, insomnia, headache, and nausea. Seven patients (3%) discontinued HCV treatment due to adverse events. No adverse effect on HIV disease or its treatment was observed. CONCLUSIONS AND RELEVANCE: In this open-label, nonrandomized, uncontrolled study, patients with HIV who were coinfected with HCV genotype 1, 2, or 3 who received the oral, interferon-free combination of sofosbuvir and ribavirin for 12 or 24 weeks had high rates of SVR12. Further studies of this oral regimen in diverse populations of coinfected patients are warranted. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01667731.

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