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Pharmacokinetics of dolutegravir and rilpivirine in combination with simeprevir and sofosbuvir in HIV/hepatitis C virus-coinfected patients with liver cirrhosis.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2017 Mar 01; Vol. 72 (3), pp. 812-815. - Publication Year :
- 2017
-
Abstract
- Objectives: 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.<br />Patients and Methods: 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.<br />Results: 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.<br />Conclusions: 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.<br /> (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Coinfection drug therapy
Coinfection virology
Drug Therapy, Combination
Female
Genotype
HIV Infections complications
Hepacivirus physiology
Hepatitis C, Chronic complications
Heterocyclic Compounds, 3-Ring administration & dosage
Heterocyclic Compounds, 3-Ring therapeutic use
Humans
Liver Cirrhosis virology
Liver Transplantation
Male
Middle Aged
Oxazines
Piperazines
Prospective Studies
Pyridones
RNA, Viral blood
Rilpivirine administration & dosage
Rilpivirine therapeutic use
Simeprevir administration & dosage
Simeprevir therapeutic use
Sofosbuvir administration & dosage
Sofosbuvir therapeutic use
Viral Load
HIV Infections drug therapy
Hepatitis C, Chronic drug therapy
Heterocyclic Compounds, 3-Ring pharmacokinetics
Liver Cirrhosis complications
Rilpivirine pharmacokinetics
Simeprevir pharmacokinetics
Sofosbuvir pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 72
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 27999010
- Full Text :
- https://doi.org/10.1093/jac/dkw492