Intravenous drug users (IVDUs) with hepatitis C (HCV) infections were successfully recruited for a study examining the feasibility of direct-acting antiviral (DAA) medications, with good results in terms of retention rates, viral responses, and patient satisfaction, indicating potential DAA utility in treatment as prevention (TasP) in those at risk of spreading the disease, according to study findings published in PLoS One.
The subset of HCV sufferers at substantial risk of transmitting infection to others includes IVDUs, in whom prevention efforts have not been satisfactory. This unfortunate reality, coupled with the availability of DAAs, has driven a TasP strategy whereby patients are treated in order to reduce secondary transmission of HCV to other individuals. However, data is limited regarding the feasibility of TasP in this high-risk group or the optimal treatment delivery approach. Investigators sought to fill this knowledge gap.
Between 2015 and 2017 in San Francisco, California, a dual-arm randomized trial (ClinicalTrials.gov ID NCT02609893) enrolled 31 patients whose test results were IVDU HCV-positive (mean age, 42.43 years; 80.6% men; 74.2% white; 77.4% unemployed; mean injection partners over 30 days, 6.2) to compare modified directly observed vs unobserved treatment with a DAA fixed-dose combination therapy. Participants were randomly assigned 2:1 to receive oral ledipasvir-sofosbuvir 80 mg/400 mg daily as an observed (n=20; mean age, 44.10 years; 80.0% men) or unobserved (n=11; mean age, 39.10 years; 81.8% men) dose for 8 weeks, followed by 36 weeks of follow-up.
Major outcomes included recruitment-enrollment statistics, therapy completion rates, virologic response rates, and reinfection rates, assessed at the end of treatment, and for the last two categories, at 12 weeks and 36 weeks. All individuals also attended weekly visits during the study.
Of the 72/83 (87.6%) eligible participants who attended the initial screening visit, 33 were selected for inclusion and 31 were enrolled in the study. Patients in the observed arm attended 89.4% of their visits, while 96.6% of unobserved patients did the same. There was a single patient from the observed group who did not complete treatment.
At the end of treatment at 8 weeks, 30/31 (96.8%) participants had no detectable HCV; at 12 weeks follow-up, 26/29 participants (89.7%) had a sustained virologic response and undetectable HCV, with 1 reinfection and 1 relapse reported. There was no significant difference in detectability between the study arms (P >.99). At week 36, 23/26 patients (88.5%) still had undetectable HCV, which led researchers to infer a 36-week sustained virologic response in 23/28 (82.1%) participants.
By the end of the 36-week follow-up period, there were 2 more reinfections recorded, yielding an overall reinfection rate of 16.3 per 100 person-years of observation. While the unobserved arm had no reinfections following 8.5 person-years of follow-up, the observed group demonstrated a reinfection rate of 25.9 per 100 person-years.
The frequency of adverse events (AEs) did not differ significantly between the study arms (P >.99). There were 3 serious AEs, none of which were related to the study drug.
All participants reported being satisfied with their experience, with 89.7% stating that the interventions helped them greatly. There were no significant differences in any satisfaction rating between groups.
Study limitations included being a pilot study, homogeneity of the population that might limit generalizability, and persistent monitoring device losses that precluded linking medication adherence to virologic response.
“The adherence to [observed] dosing and visits, as well as viral response rates, suggest that this population, even with high rates of homelessness, can be treated successfully outside of more regulated settings,” noted the investigators. They recommended that future research use alternate methods such as body fluid sampling to confirm DAA adherence.
This work was supported by the National Institute on Drug Abuse at the National Institutes of Health [grant# R34DA039333]. Study drug was donated by Gilead Sciences. Neither the funder nor the study drug provider determined the conduct of the study, the content or interpretation of data.
Phillip Coffin directed this study, which received donated study drug from Gilead Sciences. The investigators stated: “This support does not alter our adherence to PLOS ONE policies on sharing data and materials.”
Coffin PO, Santos G-M, Behar E, et al. Randomized feasibility trial of directly observed versus unobserved hepatitis C treatment with ledipasvir-sofosbuvir among people who inject drugs. PloS One. 2019;14(6):e0217471.