David L Wyles1, Peter J Ruane, Mark S Sulkowski, Douglas Dieterich, Anne Luetkemeyer, Timothy R Morgan, Kenneth E Sherman, Robin Dretler, Dawn Fishbein, Joseph C Gathe, Sarah Henn, Federico Hinestrosa, Charles Huynh, Cheryl McDonald, Anthony Mills, Edgar Turner Overton, Moti Ramgopal, Bruce Rashbaum, Graham Ray, Anthony Scarsella, Joseph Yozviak, Fiona McPhee, Zhaohui Liu, Eric Hughes, Philip D Yin, Stephanie Noviello, Peter Ackerman. 1. From the University of California, San Diego, La Jolla (D.L.W.), Ruane Medical and Liver Health Institute (P.J.R.), the Jeffrey Goodman Clinic, Los Angeles LGBT Center (C.H.), and Southern California Men's Medical Group-Men's Health Foundation (A.M.), Los Angeles, the University of California, San Francisco, San Francisco (A.L.), Veterans Affairs Long Beach Healthcare System, Long Beach (T.R.M.), and Pacific Oaks Medical Group, Beverly Hills (A.S.) - all in California; Johns Hopkins University, Lutherville, MD (M.S.S.); Icahn School of Medicine at Mount Sinai, New York (D.D.); University of Cincinnati College of Medicine, Cincinnati (K.E.S.); Infectious Disease Specialists of Atlanta, Decatur, GA (R.D.); MedStar Washington Hospital Center (D.F.), Whitman-Walker Health (S.H.), and Capital Medical Associates (B.R.) - all in Washington, DC; the Cure C Consortium, Houston (J.C.G.), and Tarrant County Infectious Disease Associates, Fort Worth (C.M.) - both in Texas; Orlando Immunology Center, Orlando (F.H.), and Midway Immunology and Research Center, Fort Pierce (M.R.) - both in Florida; the University of Alabama at Birmingham, Birmingham (E.T.O.); the University of Colorado, Denver (G.R.); Lehigh Valley Health Network, Allentown, PA (J.Y.); and Bristol-Myers Squibb, Wallingford, CT (F.M., P.D.Y., P.A.), and Princeton, NJ (Z.L., E.H., S.N.).
Abstract
BACKGROUND: The combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1). METHODS: This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1. Previously untreated patients were randomly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a standard dose of 60 mg daily (with dose adjustment for concomitant antiretroviral medications) plus 400 mg of sofosbuvir daily. Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses. The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks. RESULTS: Patients had HCV genotypes 1 through 4 (83% with genotype 1), and 14% had compensated cirrhosis; 98% were receiving antiretroviral therapy. Among patients with genotype 1, a sustained virologic response was reported in 96.4% (95% confidence interval [CI], 89.8 to 99.2) who were treated for 12 weeks and in 75.6% (95% CI, 59.7 to 87.6) who were treated for 8 weeks among previously untreated patients and in 97.7% (95% CI, 88.0 to 99.9) who were treated for 12 weeks among previously treated patients. Rates of sustained virologic response across all genotypes were 97.0% (95% CI, 91.6 to 99.4), 76.0% (95% CI, 61.8 to 86.9), and 98.1% (95% CI, 89.7 to 100), respectively. The most common adverse events were fatigue, nausea, and headache. There were no study-drug discontinuations because of adverse events. HIV-1 suppression was not compromised. CONCLUSIONS: Among previously untreated HIV-HCV coinfected patients receiving daclatasvir plus sofosbuvir for HCV infection, the rate of sustained virologic response across all genotypes was 97.0% after 12 weeks of treatment and 76.0% after 8 weeks. (Funded by Bristol-Myers Squibb; ALLY-2 ClinicalTrials.gov number, NCT02032888.).
RCT Entities:
BACKGROUND: The combination of daclatasvir, a hepatitis C virus (HCV) NS5A inhibitor, and the NS5B inhibitor sofosbuvir has shown efficacy in patients with HCV monoinfection. Data are lacking on the efficacy and safety of this combination in patients coinfected with human immunodeficiency virus type 1 (HIV-1). METHODS: This was an open-label study involving 151 patients who had not received HCV treatment and 52 previously treated patients, all of whom were coinfected with HIV-1. Previously untreated patients were randomly assigned in a 2:1 ratio to receive either 12 weeks or 8 weeks of daclatasvir at a standard dose of 60 mg daily (with dose adjustment for concomitant antiretroviral medications) plus 400 mg of sofosbuvir daily. Previously treated patients were assigned to undergo 12 weeks of therapy at the same doses. The primary end point was a sustained virologic response at week 12 after the end of therapy among previously untreated patients with HCV genotype 1 who were treated for 12 weeks. RESULTS:Patients had HCV genotypes 1 through 4 (83% with genotype 1), and 14% had compensated cirrhosis; 98% were receiving antiretroviral therapy. Among patients with genotype 1, a sustained virologic response was reported in 96.4% (95% confidence interval [CI], 89.8 to 99.2) who were treated for 12 weeks and in 75.6% (95% CI, 59.7 to 87.6) who were treated for 8 weeks among previously untreated patients and in 97.7% (95% CI, 88.0 to 99.9) who were treated for 12 weeks among previously treated patients. Rates of sustained virologic response across all genotypes were 97.0% (95% CI, 91.6 to 99.4), 76.0% (95% CI, 61.8 to 86.9), and 98.1% (95% CI, 89.7 to 100), respectively. The most common adverse events were fatigue, nausea, and headache. There were no study-drug discontinuations because of adverse events. HIV-1 suppression was not compromised. CONCLUSIONS: Among previously untreated HIV-HCV coinfectedpatients receiving daclatasvir plus sofosbuvir for HCV infection, the rate of sustained virologic response across all genotypes was 97.0% after 12 weeks of treatment and 76.0% after 8 weeks. (Funded by Bristol-Myers Squibb; ALLY-2 ClinicalTrials.gov number, NCT02032888.).
Authors: Taraz Samandari; Ellen Tedaldi; Carl Armon; Rachel Hart; Joan S Chmiel; John T Brooks; Kate Buchacz Journal: Open Forum Infect Dis Date: 2017-06-10 Impact factor: 3.835
Authors: Moisés Uriarte-Pinto; Herminia Navarro-Aznarez; Natalia De La Llama-Celis; Piedad Arazo-Garcés; Ana María Martínez-Sapiña; María Reyes Abad-Sazatornil Journal: Int J Clin Pharm Date: 2018-03-20
Authors: Basile Njei; Thomas R McCarty; Jeffrey Luk; Oforbuike Ewelukwa; Ivo Ditah; Joseph K Lim Journal: J Gastroenterol Hepatol Date: 2016-10 Impact factor: 4.029