Predictors of 007 triphosphate concentrations in dried blood spots in persons with hepatitis C and active drug or alcohol use

J Antimicrob Chemother. 2022 Apr 27;77(5):1396-1403. doi: 10.1093/jac/dkac051.


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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Dried Blood Spot Testing
  • Female
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • Hepacivirus
  • Hepatitis C* / complications
  • Hepatitis C* / drug therapy
  • Humans
  • Male
  • Polyphosphates / therapeutic use
  • Sofosbuvir / therapeutic use


  • Polyphosphates
  • triphosphoric acid
  • Sofosbuvir