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

• Published in: Journal of antimicrobial chemotherapy 2022-04, Vol.77 (5), p.1396-1403
• Main Authors: Brooks, Kristina M, Castillo-Mancilla, Jose R, Morrow, Mary, Mawhinney, Samantha, Rowan, Sarah E, Wyles, David, Blum, Joshua, Huntley, Ryan, Salah, Lana, Tehrani, Arya, Jimmerson, Leah C, Roon, Laura, Bushman, Lane R, Anderson, Peter L, Kiser, Jennifer J
• Format: Article
• Language: English
• Subjects: Dried Blood Spot Testing; Female; Hepacivirus; Hepatitis C - complications; Hepatitis C - drug therapy; HIV Infections - complications; HIV Infections - drug therapy; Humans; Male; Original Research; Polyphosphates - therapeutic use; Sofosbuvir - therapeutic use
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkac051

Abstract 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.