Randomized feasibility trial of directly observed versus unobserved hepatitis C treatment with ledipasvir-sofosbuvir among people who inject drugs

Abstract

Aims The advent of direct-acting antivirals for hepatitis C virus (HCV) and limited effectiveness of prevention have generated interest in “Treatment as Prevention” (TasP), in which those most likely to transmit HCV (i.e. people who inject drugs [PWID]) are treated to reduced secondary transmission. However, there are scant data regarding the feasibility of treating PWID at high risk for secondary transmission or the optimal approach to treatment delivery. Methods We conducted a 2:1 randomized trial of modified directly-observed (mDOT) versus unobserved HCV treatment with ledipasvir-sofosbuvir daily for 8 weeks among PWID with 36 weeks of follow-up in San Francisco from 2015–2017. We evaluated recruitment-enrollment, treatment completion, end-of-treatment and 12-week response, and reinfection rate. Results Of 83 individuals eligible for screening, 72 (87.6%) attended the screening visit, 33 were eligible, and 31 enrolled; mean age was 42 years, 81% were male, 74% white. All but one participant (in the mDOT arm) completed treatment and 89.4% of mDOT and 96.6% of unobserved arm visits were attended. HCV was undetectable for 96.8% (30/31) at end of treatment and 89.7% (26/29) 12 weeks later (1 relapse, 1 reinfection), with no differences by arm. Two additional reinfections were subsequently identified, for a reinfection rate of 16.3 (95% CI 5.3–50.5) per 100 person-years of observation. Conclusions It was feasible to recruit active PWID for HCV treatment and achieve high retention, viral response, and satisfaction with either mDOT or unobserved protocols, supporting treatment of PWID at risk of transmitting HCV to others. The reinfection rate suggests we successfully reached a high-risk population and that successful HCV TasP initiatives may aim to be sufficient in scope to significantly lower prevalence in the community. Trial registration clinicaltrials.gov NCT02609893 .

Hepatitis C Guidance 2019 Update: American Association for the Study of Liver Diseases–Infectious Diseases Society of America Recommendations for Testing, Managing, and Treating Hepatitis C Virus Infection

“…Several studies demonstrate that treatment-committed individuals in this disproportionately affected population achieve sustained virologic response (SVR) rates with DAA therapy comparable to those without known, current substance use. (73,(132)(133)(134)(135)(136)(137)(138)(139) The universal treatment recommendation represents a principal tenet of the HCV guidance along with newly recommended universal hepatitis C screening of adults. The HCV guidance panel urges health care providers caring for adults to encourage hepatitis C screening and treatment (if positive) because DAA therapy is safe and cures HCV infection in most people.…”

“…Importantly, this recommendation includes persons with ongoing substance use (alcohol or drugs). Several studies demonstrate that treatment‐committed individuals in this disproportionately affected population achieve sustained virologic response (SVR) rates with DAA therapy comparable to those without known, current substance use . The universal treatment recommendation represents a principal tenet of the HCV guidance along with newly recommended universal hepatitis C screening of adults.…”

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

“…Ingestible sensor systems in persons with HCV demonstrated mean adherence rates of 93%–97% [ 29 , 30 ], but large-scale overencapsulation of medication tablets may be challenging to implement. Modified DOT strategies comprising in-person DOT during OAT clinic visits and either self-administered tablets [ 31 ] or electronic monitoring [ 15 , 32 ] outside of clinic have been detailed, with mean adherence rates of 86%–95%. In-person DOT may be burdensome to coordinate outside of OAT clinic settings.…”

Patient Centeredness in Hepatitis C Direct-Acting Antiviral Treatment Delivery to People Who Inject Drugs: A Scoping Review

“…Eleven studies co-located HCV treatment point of care with other services. These services included primary care services [36,41,42], homeless primary care services [26], SAM clinics [41,43,44], harm reduction centers [45][46][47], public health services [48], and HIV clinics [49].…”

“…Clinical Visits Follow-up support to ensure adherence was the most addressed component within this dimension (19 studies). This follow-up was offered by providers [31,33,37,39,40,42,43,45,46,48,[50][51][52]58] as well as peer support groups [26,53,56]. One study triaged the patients into different levels of support according to their risk of non-adherence and patients who did not complete treatment were offered intensive follow-up home visits by peers [57].…”