title: Pharmacokinetics of dolutegravir and rilpivirine in combination with simeprevir and sofosbuvir in HIV/hepatitis C virus-coinfected patients with liver cirrhosis.
abstract: To evaluate the plasma trough concentrations ( C trough ) of dolutegravir and rilpivirine used in combination with simeprevir and sofosbuvir in HIV/hepatitis C virus (HCV)-coinfected patients with liver cirrhosis. Virological efficacy and safety of both ART and anti-HCV therapy were assessed.
  
  
  
  A prospective observational study in HIV/HCV-coinfected patients with liver cirrhosis on ART with dolutegravir plus rilpivirine and treated with simeprevir plus sofosbuvir (±ribavirin) was conducted. Dolutegravir, rilpivirine, GS-331007 (sofosbuvir metabolite) and simeprevir C trough were evaluated with a validated HPLC method at anti-HCV treatment baseline and weeks 2 and 4. Geometric means were calculated to summarize C trough values.
  
  
  
  Twelve patients were evaluated: 75% were males and the median (IQR) age was 53 (53-55) years. All patients were Child-Pugh stage A, except one who was stage B. The geometric mean (95% CI) of C trough of rilpivirine and dolutegravir did not change between baseline and week 4 ( P  =   0.654 and P  =   0.268, respectively), with corresponding overall values of 135 (102-177) and 1357 (970-1897) ng/mL. The overall geometric mean (95% CI) of GS-331007 and simeprevir C trough was 370 (268-512) and 2537 (1569-4101) ng/mL, respectively, without significant variation between weeks 2 and 4 ( P  =   0.643 and P  =   0.179, respectively). All patients completed anti-HCV treatment, achieving sustained virological response. All but two patients maintained undetectable HIV-RNA up to post-treatment week 24.
  
  
  
  Dolutegravir and rilpivirine C trough appeared not to be affected by concomitant treatment with simeprevir plus sofosbuvir in these HIV/HCV-coinfected patients with liver cirrhosis, supporting the use of this antiretroviral regimen in this setting.
authors.affiliation: Infectious Diseases Clinic, IRCCS San Raffaele Hospital, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Merli
authors.affiliation: Infectious Diseases Clinic, IRCCS San Raffaele Hospital, Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Galli
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Marinaro
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ariaudo
authors.affiliation: Infectious Diseases Clinic, IRCCS San Raffaele Hospital, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Messina
authors.affiliation: Infectious Diseases Clinic, IRCCS San Raffaele Hospital, Milan, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Uberti-Foppa
authors.affiliation: Infectious Diseases Clinic, IRCCS San Raffaele Hospital, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Castagna
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
authors.affiliation: Infectious Diseases Clinic, IRCCS San Raffaele Hospital, Milan, Italy.|Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Adriano
authors.initials: A
authors.lastname: Lazzarin
authors.affiliation: Department of Medical Sciences, University of Turin, Turin, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.affiliation: Infectious Diseases Clinic, IRCCS San Raffaele Hospital, Milan, Italy.
authors.forename: Hamid
authors.initials: H
authors.lastname: Hasson
mesh_terms: D060085:Coinfection / Q000188:drug therapy / Q000821:virology; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D016174:Hepacivirus / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006575:Heterocyclic Compounds, 3-Ring / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000821:virology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D010078:Oxazines; D010879:Piperazines; D011446:Prospective Studies; D011728:Pyridones; D012367:RNA, Viral / Q000097:blood; D000068696:Rilpivirine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069616:Simeprevir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069474:Sofosbuvir / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019562:Viral Load; D000099226:Dolutegravir
chemical_list: D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D012367:RNA, Viral; D000068696:Rilpivirine; D000069616:Simeprevir; D000069474:Sofosbuvir; D000099226:Dolutegravir