Adherence to Once-daily and Twice-daily Direct-acting Antiviral Therapy for Hepatitis C Infection Among People With Recent Injection Drug Use or Current Opioid Agonist Therapy
Authors: Cunningham Evan B , Hajarizadeh Behzad , Amin Janaki , Litwin Alain H , Gane Edward , Cooper Curtis , Lacombe Karine , Hellard Margaret , Read Phillip , Powis Jeff , Dalgard Olav , Bruneau Julie , Matthews Gail V , Feld Jordan J , Dillon John F , Shaw David , Bruggmann Philip , Conway Brian , Fraser Chris , Marks Philippa , Dore Gregory J , Grebely Jason ,   SIMPLIFY and D3FEAT study groups, Grebely Jason , Dore Gregory , Dalgard Olav , Bruggmann Philip , Stedman Catherine , Lacombe Karine , Powis Jeff , Hellard Margaret , Crawford Sione , Swan Tracy , Byrne Jude , Lacalamita Melanie , Cunningham Evan , Hajarizadeh Behzad , Grebely Jason , Dore Gregory , Marks Pip , Shaw Ineke , Siriragavan Sharmila , Amin Janaki , Quiene Sophie , Petoumenos Kathy , Schmid Patrick , Castro Erika , Moriggia Alberto , Lacombe Karine , Daulouede Jean-Pierre , Dalgard Olav , Conway Brian , Fraser Christopher , Powis Jeff , Feld Jordan , Bruneau Julie , Cooper Curtis , Gane Ed , Stedman Catherine , Matthews Gail , Dunlop Adrian , Hellard Margaret , Kronborg Ian , Shaw David , Litwin Alain , Thurnheer Maria Christine , Weltman Martin , Read Philip , Dillon John , Kessler Simone , Knapp Cornelia , Oprandi Lorenza , Messina Paola , Pantic Marzia , Cam Manuela Le , Maitre Cecilia , Andreassen Jessica , Melkeraaen Ingunn , Tollefsen Merete Moen , Pagarigan Hannah , Milne Rozalyn , Mason Kate , Kaznowski Diana , Zou Lily , Bouchard Rachel , Kotsoros Barbara , Muir Miriam , Milloy Jessica , Oliver Victoria , Noonan Tracy , Sevehon Alison , Hazelwood Susan , Hall Michelle , Hagenauer Michelle , Liddle Rachel , Ferguson Catherine , Agyemang Linda , Patel Hiral , Soloway Irene , Cerocchi Orlando , Lacalamita Melanie , Fragomeli Vincenzo , Gilliver Rosie , Lothian Rebecca , Cleary Shirley , Johnston Linda , Middleton Sarah , Brainard Diana , McHutchison John , Grebely Jason , Dore Gregory , Dalgard Olav , Bruggmann Philip , Stedman Catherine , Lacombe Karine , Powis Jeff , Hellard Margaret , Crawford Sione , Swan Tracy , Byrne Jude , Lacalamita Melanie , Cunningham Evan , Hajarizadeh Behzad , Grebely Jason , Dore Gregory , Marks Pip , Shaw Ineke , Siriragavan Sharmila , Amin Janaki , Quiene Sophie , Petoumenos Kathy , Schmid Patrick , Castro Erika , Moriggia Alberto , Lacombe Karine , Daulouede Jean-Pierre , Dalgard Olav , Conway Brian , Fraser Christopher , Powis Jeff , Feld Jordan , Bruneau Julie , Cooper Curtis , Gane Ed , Stedman Catherine , Matthews Gail , Dunlop Adrian , Hellard Margaret , Kronborg Ian , Shaw David , Litwin Alain , Thurnheer Maria Christine , Weltman Martin , Read Philip , Dillon John , Kessler Simone , Knapp Cornelia , Oprandi Lorenza , Messina Paola , Pantic Marzia , Cam Manuela Le , Maitre Cecilia , Andreassen Jessica , Melkeraaen Ingunn , Tollefsen Merete Moen , Pagarigan Hannah , Milne Rozalyn , Mason Kate , Kaznowski Diana , Zou Lily , Bouchard Rachel , Kotsoros Barbara , Muir Miriam , Milloy Jessica , Oliver Victoria , Noonan Tracy , Sevehon Alison , Hazelwood Susan , Hall Michelle , Hagenauer Michelle , Liddle Rachel , Ferguson Catherine , Agyemang Linda , Patel Hiral , Soloway Irene , Cerocchi Orlando , Lacalamita Melanie , Fragomeli Vincenzo , Gilliver Rosie , Lothian Rebecca , Cleary Shirley , Johnston Linda , Middleton Sarah , Brainard Diana , McHutchison John 
Published: November 2019

Abstract

Background
This study investigated adherence and associated factors among people with recent injection drug use (IDU) or current opioid agonist therapy (OAT) and compared once-daily to twice-daily hepatitis C virus (HCV) direct-acting antiviral (DAA) therapy.

Methods
SIMPLIFY and D3FEAT are international, multicenter studies that recruited participants with recent IDU (previous 6 months; SIMPLIFY, D3FEAT) or current OAT (D3FEAT) between March 2016 and February 2017 in 8 countries. Participants received sofosbuvir/velpatasvir (once daily; SIMPLIFY) or paritaprevir/ritonavir/ombitasvir, dasabuvir (twice daily) ± ribavirin (D3FEAT) for 12 weeks administered in electronic blister packs. We evaluated overall adherence (proportion of prescribed doses taken) and nonadherence (&lt;90% adherent) between dosing patterns.

Results
Of 190 participants, 184 (97%) completed treatment. Median adherence was 92%, with higher adherence among those receiving once-daily vs twice-daily therapy (94% vs 87%, P = .005). Overall, 40% of participants (n = 76) were nonadherent (&lt;90% adherent). Recent stimulant injecting (odds ratio [OR], 2.48 [95% confidence interval {CI}, 1.28–4.82]), unstable housing (OR, 2.18 [95% CI, 1.01–4.70]), and twice-daily dosing (OR, 2.81 [95% CI, 1.47–5.36]) were associated with nonadherence. Adherence decreased during therapy. Sustained virologic response was high in nonadherent (89%) and adherent populations (95%, P = .174), with no difference in SVR between those who did and did not miss 7 consecutive doses (92% vs 93%, P = .897).

Conclusions
This study demonstrated high adherence to once- and twice-daily DAA therapy among people with recent IDU or currently receiving OAT. Nonadherence described did not impact treatment outcomes, suggesting forgiveness to nonadherence.