Predictors of 007 triphosphate concentrations in dried blood spots in persons with hepatitis C and active drug or alcohol use.
Journal
The Journal of antimicrobial chemotherapy
ISSN: 1460-2091
Titre abrégé: J Antimicrob Chemother
Pays: England
ID NLM: 7513617
Informations de publication
Date de publication:
27 04 2022
27 04 2022
Historique:
received:
20
09
2021
accepted:
12
01
2022
pubmed:
24
2
2022
medline:
3
5
2022
entrez:
23
2
2022
Statut:
ppublish
Résumé
Sofosbuvir is converted to its active form, 007 triphosphate (007-TP), within cells. To date, the association between treatment adherence and 007-TP in dried blood spots (DBS) and factors that influence this relationship remain unknown. To examine relationships between adherence and 007-TP concentrations in DBS and identify factors that influence 007-TP in DBS. Persons with HCV or HIV/HCV coinfection and self-reported drug and/or alcohol use were randomized to one of two technology-based approaches for monitoring 12 week adherence to once-daily ledipasvir/sofosbuvir. Convenience blood samples were collected every 2 weeks during treatment. 007-TP in DBS was quantified using LC/MS and analysed using mixed-effects models. A total of 337 observations were available from 58 participants (78% male; 21% black; 22% Hispanic/Latino; 26% cirrhotic; 78% HIV-coinfected). The mean half-life of 007-TP in DBS was 142 h (95% CI 127-156) and concentrations increased by 7.3% (95% CI 2.2-12.6) for every 10% increase in between-visit adherence. Geometric mean (95% CI) 007-TP concentrations in DBS were 301 (247-368), 544 (462-639) and 647 (571-723) fmol/punch by adherence categories of ≤50%, >50 to ≤80%, and >80%. Adherence, time on therapy, increasing age and decreased estimated glomerular filtration rate were associated with higher 007-TP, whereas increased time since last dose, male sex, black race and higher BMI were associated with lower 007-TP. 007-TP has an extended half-life in DBS and concentrations increased with adherence. Further research is needed to examine additional factors that affect 007-TP and the clinical utility of this measure.
Sections du résumé
BACKGROUND
Sofosbuvir is converted to its active form, 007 triphosphate (007-TP), within cells. To date, the association between treatment adherence and 007-TP in dried blood spots (DBS) and factors that influence this relationship remain unknown.
OBJECTIVES
To examine relationships between adherence and 007-TP concentrations in DBS and identify factors that influence 007-TP in DBS.
METHODS
Persons with HCV or HIV/HCV coinfection and self-reported drug and/or alcohol use were randomized to one of two technology-based approaches for monitoring 12 week adherence to once-daily ledipasvir/sofosbuvir. Convenience blood samples were collected every 2 weeks during treatment. 007-TP in DBS was quantified using LC/MS and analysed using mixed-effects models.
RESULTS
A total of 337 observations were available from 58 participants (78% male; 21% black; 22% Hispanic/Latino; 26% cirrhotic; 78% HIV-coinfected). The mean half-life of 007-TP in DBS was 142 h (95% CI 127-156) and concentrations increased by 7.3% (95% CI 2.2-12.6) for every 10% increase in between-visit adherence. Geometric mean (95% CI) 007-TP concentrations in DBS were 301 (247-368), 544 (462-639) and 647 (571-723) fmol/punch by adherence categories of ≤50%, >50 to ≤80%, and >80%. Adherence, time on therapy, increasing age and decreased estimated glomerular filtration rate were associated with higher 007-TP, whereas increased time since last dose, male sex, black race and higher BMI were associated with lower 007-TP.
CONCLUSIONS
007-TP has an extended half-life in DBS and concentrations increased with adherence. Further research is needed to examine additional factors that affect 007-TP and the clinical utility of this measure.
Identifiants
pubmed: 35194648
pii: 6534629
doi: 10.1093/jac/dkac051
pmc: PMC9633722
doi:
Substances chimiques
Polyphosphates
0
triphosphoric acid
NU43IAG5BC
Sofosbuvir
WJ6CA3ZU8B
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1396-1403Subventions
Organisme : NIDA NIH HHS
ID : R01 DA040499
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002535
Pays : United States
Informations de copyright
© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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