Plasma trough concentrations of antiretrovirals in HIV-infected persons treated with direct-acting antiviral agents for hepatitis C in the real world

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Abstract

Background: Possible drug-drug interactions (DDIs) between antiretrovirals (ARVs) and direct-acting antiviral agents (DAAs) are of some concern. Objectives: To investigate ARV plasma trough concentrations (Ctrough) before and during DAAs in patients treated in the real world. Methods: Single-centre, prospective, observational study including HIV/HCV coinfected persons undergoing DAA treatment. Self-reported adherence was assessed and ARVs Ctrough measured by HPLC-UV. Blood samples were collected before and after 2months of DAA treatment. Results: One-hundred and thirty-seven patients were included: 21.2% treated with ombitasvir/paritaprevir/ ritonavir+dasabuvir (2D/3D) and 78.8% with sofosbuvir-based regimens. Suboptimal Ctrough before and during DAA was found, respectively, in 3 (10.3%) and 3 (10.3%) cases treated with 2D/3D, and 16 (14.8%) and 11 (10.2%) with sofosbuvir-based regimens, even if self-reported ARV adherence was always ≥ 93%. In 2D/3Dtreated patients, median darunavir Ctrough during DAAs was significantly lower than observed before DAAs [1125 ng/mL (IQR, 810-1616) versus 1903ng/mL (IQR 1387-3983), respectively] (n=5; P=0.009), with a 40.9% decrease. In the same group, no differences in atazanavir or raltegravir concentrations were found. In patients treated with sofosbuvir-based regimens, Ctrough of all ARVs were similar before and during DAAs. Conclusions: In the real world of HIV/HCV coinfected patients, ARV plasma concentrations during DAAs were generally not different from those found before anti-HCV treatment. Although assessed in a small number of patients, darunavir concentrations during 2D/3D showed a significant reduction when compared with those found before DAAs. ARV plasma concentrations measurement during anti-HCV treatment may give useful information for managing HIV/HCV coinfected persons receiving treatment for both infections.

Original languageEnglish
Article numberdkx348
Pages (from-to)1-5
Number of pages5
JournalJournal of Antimicrobial Chemotherapy
DOIs
Publication statusE-pub ahead of print - Nov 2 2017

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Hepatitis C
Antiviral Agents
HIV
Therapeutics
Ritonavir
Drug Interactions
Observational Studies
High Pressure Liquid Chromatography
Prospective Studies

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

@article{38d796dd50c7434d96d2f96d6c8c325d,
title = "Plasma trough concentrations of antiretrovirals in HIV-infected persons treated with direct-acting antiviral agents for hepatitis C in the real world",
abstract = "Background: Possible drug-drug interactions (DDIs) between antiretrovirals (ARVs) and direct-acting antiviral agents (DAAs) are of some concern. Objectives: To investigate ARV plasma trough concentrations (Ctrough) before and during DAAs in patients treated in the real world. Methods: Single-centre, prospective, observational study including HIV/HCV coinfected persons undergoing DAA treatment. Self-reported adherence was assessed and ARVs Ctrough measured by HPLC-UV. Blood samples were collected before and after 2months of DAA treatment. Results: One-hundred and thirty-seven patients were included: 21.2{\%} treated with ombitasvir/paritaprevir/ ritonavir+dasabuvir (2D/3D) and 78.8{\%} with sofosbuvir-based regimens. Suboptimal Ctrough before and during DAA was found, respectively, in 3 (10.3{\%}) and 3 (10.3{\%}) cases treated with 2D/3D, and 16 (14.8{\%}) and 11 (10.2{\%}) with sofosbuvir-based regimens, even if self-reported ARV adherence was always ≥ 93{\%}. In 2D/3Dtreated patients, median darunavir Ctrough during DAAs was significantly lower than observed before DAAs [1125 ng/mL (IQR, 810-1616) versus 1903ng/mL (IQR 1387-3983), respectively] (n=5; P=0.009), with a 40.9{\%} decrease. In the same group, no differences in atazanavir or raltegravir concentrations were found. In patients treated with sofosbuvir-based regimens, Ctrough of all ARVs were similar before and during DAAs. Conclusions: In the real world of HIV/HCV coinfected patients, ARV plasma concentrations during DAAs were generally not different from those found before anti-HCV treatment. Although assessed in a small number of patients, darunavir concentrations during 2D/3D showed a significant reduction when compared with those found before DAAs. ARV plasma concentrations measurement during anti-HCV treatment may give useful information for managing HIV/HCV coinfected persons receiving treatment for both infections.",
author = "Massimo Tempestilli and Gabriele Fabbri and Ilaria Mastrorosa and Laura Timelli and Stefania Notari and Rita Bellagamba and Raffaella Libertone and Federico Lupi and Mauro Zaccarelli and Andrea Antinori and Chiara Agrati and Adriana Ammassari",
year = "2017",
month = "11",
day = "2",
doi = "10.1093/jac/dkx348",
language = "English",
pages = "1--5",
journal = "Journal of Antimicrobial Chemotherapy",
issn = "0305-7453",
publisher = "Oxford University Press",

}

TY - JOUR

T1 - Plasma trough concentrations of antiretrovirals in HIV-infected persons treated with direct-acting antiviral agents for hepatitis C in the real world

AU - Tempestilli, Massimo

AU - Fabbri, Gabriele

AU - Mastrorosa, Ilaria

AU - Timelli, Laura

AU - Notari, Stefania

AU - Bellagamba, Rita

AU - Libertone, Raffaella

AU - Lupi, Federico

AU - Zaccarelli, Mauro

AU - Antinori, Andrea

AU - Agrati, Chiara

AU - Ammassari, Adriana

PY - 2017/11/2

Y1 - 2017/11/2

N2 - Background: Possible drug-drug interactions (DDIs) between antiretrovirals (ARVs) and direct-acting antiviral agents (DAAs) are of some concern. Objectives: To investigate ARV plasma trough concentrations (Ctrough) before and during DAAs in patients treated in the real world. Methods: Single-centre, prospective, observational study including HIV/HCV coinfected persons undergoing DAA treatment. Self-reported adherence was assessed and ARVs Ctrough measured by HPLC-UV. Blood samples were collected before and after 2months of DAA treatment. Results: One-hundred and thirty-seven patients were included: 21.2% treated with ombitasvir/paritaprevir/ ritonavir+dasabuvir (2D/3D) and 78.8% with sofosbuvir-based regimens. Suboptimal Ctrough before and during DAA was found, respectively, in 3 (10.3%) and 3 (10.3%) cases treated with 2D/3D, and 16 (14.8%) and 11 (10.2%) with sofosbuvir-based regimens, even if self-reported ARV adherence was always ≥ 93%. In 2D/3Dtreated patients, median darunavir Ctrough during DAAs was significantly lower than observed before DAAs [1125 ng/mL (IQR, 810-1616) versus 1903ng/mL (IQR 1387-3983), respectively] (n=5; P=0.009), with a 40.9% decrease. In the same group, no differences in atazanavir or raltegravir concentrations were found. In patients treated with sofosbuvir-based regimens, Ctrough of all ARVs were similar before and during DAAs. Conclusions: In the real world of HIV/HCV coinfected patients, ARV plasma concentrations during DAAs were generally not different from those found before anti-HCV treatment. Although assessed in a small number of patients, darunavir concentrations during 2D/3D showed a significant reduction when compared with those found before DAAs. ARV plasma concentrations measurement during anti-HCV treatment may give useful information for managing HIV/HCV coinfected persons receiving treatment for both infections.

AB - Background: Possible drug-drug interactions (DDIs) between antiretrovirals (ARVs) and direct-acting antiviral agents (DAAs) are of some concern. Objectives: To investigate ARV plasma trough concentrations (Ctrough) before and during DAAs in patients treated in the real world. Methods: Single-centre, prospective, observational study including HIV/HCV coinfected persons undergoing DAA treatment. Self-reported adherence was assessed and ARVs Ctrough measured by HPLC-UV. Blood samples were collected before and after 2months of DAA treatment. Results: One-hundred and thirty-seven patients were included: 21.2% treated with ombitasvir/paritaprevir/ ritonavir+dasabuvir (2D/3D) and 78.8% with sofosbuvir-based regimens. Suboptimal Ctrough before and during DAA was found, respectively, in 3 (10.3%) and 3 (10.3%) cases treated with 2D/3D, and 16 (14.8%) and 11 (10.2%) with sofosbuvir-based regimens, even if self-reported ARV adherence was always ≥ 93%. In 2D/3Dtreated patients, median darunavir Ctrough during DAAs was significantly lower than observed before DAAs [1125 ng/mL (IQR, 810-1616) versus 1903ng/mL (IQR 1387-3983), respectively] (n=5; P=0.009), with a 40.9% decrease. In the same group, no differences in atazanavir or raltegravir concentrations were found. In patients treated with sofosbuvir-based regimens, Ctrough of all ARVs were similar before and during DAAs. Conclusions: In the real world of HIV/HCV coinfected patients, ARV plasma concentrations during DAAs were generally not different from those found before anti-HCV treatment. Although assessed in a small number of patients, darunavir concentrations during 2D/3D showed a significant reduction when compared with those found before DAAs. ARV plasma concentrations measurement during anti-HCV treatment may give useful information for managing HIV/HCV coinfected persons receiving treatment for both infections.

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DO - 10.1093/jac/dkx348

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