Adherence to Direct-Acting Antiviral Therapy in People Actively Using Drugs and Alcohol: The INCLUD Study

Abstract

Background HCV treatment in persons who use drugs (PWUD) is often withheld due to adherence and reinfection concerns. Here, we report treatment outcomes, technology-based adherence data, and adherence predictors in PWUD and/or alcohol. Methods INCLUD was a prospective, open-label study of ledipasvir/sofosbuvir for 12 weeks in PWUD aged 18-70 years. Participants were randomized to wireless (WOT, Wisepill®) or video-based directly observed therapy (vDOT, Emocha®). Drug use was assessed every 2 weeks. Sustained virologic response (SVR) was examined by intention-to-treat and as-treated. Factors associated with missing ≥1 dose(s) between visits were examined using generalized linear models. Results Sixty participants received ≥1 ledipasvir/sofosbuvir dose (47 HIV/HCV, 13 HCV only; 78% male; 22% Black; 25% cirrhotic). Substance use occurred at 94% of person-visits: 60% marijuana, 56% alcohol, 37% methamphetamine, 22% opioids, 17% cocaine, and 20% injection drug use. SVR by intention-to-treat was 86.7% (52/60) and as-treated was 94.5% (52/55). Confirmed failures included 1 relapse, 1 reinfection, and 1 unknown (suspected reinfection). Median (IQR [range]) total adherence was 96% (85-100% [30-101%]) and between-visit adherence was 100% (86-100% [0-107%]). Odds [95% CI] of missing ≥1 dose between visits increased with HIV coinfection (2.94 [1.37, 6.32], p=0.006), Black race (4.09 [1.42, 11.74], p=0.009), methamphetamine use (2.51 [1.44, 4.37], p=0.0.001) and cocaine use (2.12 [1.08, 4.18], p=0.03), and decreased with marijuana use (0.34 [0.17, 0.70], p=0.003) and vDOT (0.43 [0.21, 0.87], p=0.02). Conclusions PWUD achieved high SVR rates with high, but variable, ledipasvir/sofosbuvir adherence using technology-based methods. These findings support efforts to expand HCV treatment in PWUD.

Real‐world effectiveness and safety of direct‐acting antivirals in patients with cirrhosis and history of hepatic decompensation: Epi‐Ter2 Study

“…Not surprisingly, since patients without history of decompensated liver disease constituted the majority of the study group, similar trend was observed in the overall population analysis. The impact of non‐adherence to the treatment, dose modification or disruption on SVR has been investigated predominantly in people with injection drug use or opioid agonist therapy, for whom SVR rates were high in both nonadherent and adherent populations over a range of adherence values from 30%‐101% 53,54 . On the other hand, it is true that some studies demonstrated little room for "forgiveness" in case of non‐adherence.…”

“…The impact of non-adherence to the treatment, dose modification or disruption on SVR has been investigated predominantly in people with injection drug use or opioid agonist therapy, for whom SVR rates were high in both nonadherent and adherent populations over a range of adherence values from 30%-101%. 53,54 On the other hand, it is true that some studies demonstrated little room for "forgiveness" in case of non-adherence. An analysis of randomized controlled trials reported 96.2% adherence to ledipasvir/sofosbuvir, with an SVR rate of 97.1% in adherent patients (taking > 80% of prescribed doses) and 82.5% in nonadherent patients (P <.0001).…”

Development and Validation of a Questionnaire to Measure Medication Adherence to Direct-Acting Agents in Patients with Hepatitis C

“…I do not expect miracles after starting my treatment. 18. I strictly respect what the doctor tells me.…”

“…Studies so far have focused on pill counts (PC) [14], the use of Visual Analog Scale (VAS) [15] and mostly pharmacy records [16,17], which help to construct a general idea in specific situations over medication adherence. The number of wireless pillbox openings or video-recorded ingestions was used for DAA adherence monitoring [18]. However, other factors should be considered too, such as previous treatment experience, which may generate medication administration fear, as well as multi-tablet therapy by adding more medication to their previous treated comorbidities [19].…”

Outcomes of real-world integrated HCV microelimination for people who inject drugs: an expansion of the punjab model

“…The PWID populations in India show wide variation in socio-demographic characteristics, awareness of HIV and viral hepatitis, social acceptance of therapy and deaddiction services, type of drug use or injection patterns and social stigma [14] . A combined approach, task shifting, decentralized approach with linked services is essential to improve adherence [15] . To this end, the Mukh Mantri Punjab Hepatitis C Relief Fund (MMPHCRF) program provides algorithm-based, free- of-charge generic, all-oral DAAs therapy in the state of Punjab, a model that was replicated across the country under the National Viral Hepatitis Elimination Programme (NVHCP) [4 , 16] .…”