TY - JOUR
T1 - Virologic response following combined ledipasvir and sofosbuvir administration in patients with HCV genotype 1 and HIVCo-infection
AU - Osinusi, Anu
AU - Townsend, Kerry
AU - Kohli, Anita
AU - Nelson, Amy
AU - Seamon, Cassie
AU - Meissner, Eric G.
AU - Bon, Dimitra
AU - Silk, Rachel
AU - Gross, Chloe
AU - Price, Angie
AU - Sajadi, Mohammad
AU - Sidharthan, Sreetha
AU - Sims, Zayani
AU - Herrmann, Eva
AU - Hogan, John
AU - Teferi, Gebeyehu
AU - Talwani, Rohit
AU - Proschan, Michael
AU - Jenkins, Veronica
AU - Kleiner, David E.
AU - Wood, Brad J.
AU - Subramanian, G. Mani
AU - Pang, Phillip S.
AU - McHutchison, John G.
AU - Polis, Michael A.
AU - Fauci, Anthony S.
AU - Masur, Henry
AU - Kottilil, Shyam
N1 - Publisher Copyright:
Copyright 2015 American Medical Association. All rights reserved.
PY - 2014/3/24
Y1 - 2014/3/24
N2 - IMPORTANCE: There is an unmet need for interferon- and ribavirin-free treatment for chronic hepatitis C virus (HCV) infection in patients co-infected with human immunodeficiency virus (HIV). OBJECTIVE: To evaluate the rates of sustained virologic response (SVR) and adverse events in previously untreated patients with HCV genotype 1 and HIV co-infection following a 12-week treatment of the fixed-dose combination of ledipasvir and sofosbuvir. DESIGN, SETTING, AND PARTICIPANTS: Open-label, single-center, phase 2b pilot study of previously untreated, noncirrhotic patients with HCV genotype 1 and HIV co-infection conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, from June 2013 to September 2014. Patients included those receiving antiretroviral therapy with HIV RNA values of 50 copies/mL or fewer and a CD4 T-lymphocyte count of 100 cells/mL or greater or patients with untreated HIV infection with a CD4 T-lymphocyte count of 500 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed. INTERVENTIONS: Fifty patients with HCV genotype 1 never before treated for HCV were prescribed a fixed-dose combination of ledipasvir (90mg) and sofosbuvir (400mg) once daily for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary study outcomewas the proportion of patients with sustained viral response (plasma HCV RNA level <12 IU/mL) 12 weeks after end of treatment. RESULTS: Forty-nine of 50 participants (98%[95%CI, 89%to 100%]) achieved SVR 12 weeks after end of treatment, whereas 1 patient experienced relapse at week 4 following treatment. In the patient with relapse, deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors, such as ledipasvir. The most common adverse events were nasal congestion (16%of patients) andmyalgia (14%). There were no discontinuations or serious adverse events attributable to study drug. CONCLUSIONS AND RELEVANCE: In this open-label, uncontrolled, pilot study enrolling patients co-infected with HCV genotype 1 and HIV, administration of an oral combination of ledipasvir and sofosbuvir for 12 weeks was associated with high rates of SVR after treatment completion. Larger studies that also include patients with cirrhosis and lower CD4 T-cell counts are required to understand if the results of this study generalize to all patients co-infected with HCV and HIV.
AB - IMPORTANCE: There is an unmet need for interferon- and ribavirin-free treatment for chronic hepatitis C virus (HCV) infection in patients co-infected with human immunodeficiency virus (HIV). OBJECTIVE: To evaluate the rates of sustained virologic response (SVR) and adverse events in previously untreated patients with HCV genotype 1 and HIV co-infection following a 12-week treatment of the fixed-dose combination of ledipasvir and sofosbuvir. DESIGN, SETTING, AND PARTICIPANTS: Open-label, single-center, phase 2b pilot study of previously untreated, noncirrhotic patients with HCV genotype 1 and HIV co-infection conducted at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, from June 2013 to September 2014. Patients included those receiving antiretroviral therapy with HIV RNA values of 50 copies/mL or fewer and a CD4 T-lymphocyte count of 100 cells/mL or greater or patients with untreated HIV infection with a CD4 T-lymphocyte count of 500 cells/mL or greater. Serial measurements of safety parameters, virologic and host immune correlates, and adherence were performed. INTERVENTIONS: Fifty patients with HCV genotype 1 never before treated for HCV were prescribed a fixed-dose combination of ledipasvir (90mg) and sofosbuvir (400mg) once daily for 12 weeks. MAIN OUTCOMES AND MEASURES: The primary study outcomewas the proportion of patients with sustained viral response (plasma HCV RNA level <12 IU/mL) 12 weeks after end of treatment. RESULTS: Forty-nine of 50 participants (98%[95%CI, 89%to 100%]) achieved SVR 12 weeks after end of treatment, whereas 1 patient experienced relapse at week 4 following treatment. In the patient with relapse, deep sequencing revealed a resistance associated mutation in the NS5A region conferring resistance to NS5A inhibitors, such as ledipasvir. The most common adverse events were nasal congestion (16%of patients) andmyalgia (14%). There were no discontinuations or serious adverse events attributable to study drug. CONCLUSIONS AND RELEVANCE: In this open-label, uncontrolled, pilot study enrolling patients co-infected with HCV genotype 1 and HIV, administration of an oral combination of ledipasvir and sofosbuvir for 12 weeks was associated with high rates of SVR after treatment completion. Larger studies that also include patients with cirrhosis and lower CD4 T-cell counts are required to understand if the results of this study generalize to all patients co-infected with HCV and HIV.
UR - http://www.scopus.com/inward/record.url?scp=84925436650&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925436650&partnerID=8YFLogxK
U2 - 10.1001/jama.2015.1373
DO - 10.1001/jama.2015.1373
M3 - Article
C2 - 25706232
AN - SCOPUS:84925436650
SN - 0098-7484
VL - 313
SP - 1232
EP - 1239
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
IS - 12
ER -