Methamphetamine use and illicit opioid use during buprenorphine treatment.

Introduction: Although methamphetamine use is rising in the United States, its impacts on patient outcomes among persons undergoing treatment for opioid use disorder (OUD) remain unclear. This study aims to assess the association between baseline methamphetamine/amphetamine (MA/A) use and subsequent illicit opioid use among patients with OUD initiating buprenorphine in an office-based setting. Methods: We conducted a secondary analysis of a pilot randomized controlled trial of a behavioral mobile health intervention for buprenorphine adherence conducted over a 12-week study period at two clinic sites. The study defined baseline MA/A use by a positive urine drug test (UDT) and/or self-report of use within the past 30-days. Separate Poisson regression models with robust standard errors evaluated associations between MA/A and: i) illicit opioid use measured by weekly UDT (primary) and ii) self-reported past 30-day use at end of study (secondary). Other secondary outcomes included buprenorphine positive UDTs throughout the study and retention in OUD treatment at both weeks 12 and 24 post-randomization. Results: At baseline, 28 (36%) of the 78 participants had MA/A use and use was associated with a statistically significant increase in risk of testing positive for illicit opioids on UDT during the study follow-up period (adjusted relative risk (aRR)=1.54; 95% CI=1.09-2.17; p=0.015), as well as an increased risk for reported past 30-day illicit opioid use at week 12 (aRR=3.86; 95% CI=1.47-10.18; P=0.006). The study found no significant associations between MA/A use and buprenorphine positive UDT or retention in OUD treatment. Conclusions: In this sample of patients initiating buprenorphine, methamphetamine/amphetamine use at baseline was associated with illicit opioid use over a 12-week period. These findings demonstrate how co-use of methamphetamine can impede attainment of ideal OUD treatment outcomes.

Timing of hepatitis C treatment initiation and retention in office-based opioid treatment with buprenorphine: a retrospective cohort study.

BACKGROUND: This study examined associations between receipt of hepatitis C (HCV) treatment and retention in office-based opioid treatment (OBOT) care. METHODS: We conducted a retrospective cohort study of HCV-infected patients who initiated OBOT treatment between December 2015 and March 2021 to characterize HCV treatment and assess associations with OBOT retention. HCV treatment was characterized as no treatment, early treatment (< 100 days since OBOT initiation) or late treatment (≥ 100 days). We evaluated associations between HCV treatment and cumulative days in OBOT. A secondary analysis using Cox Proportional Hazards regression was done to determine the rate of discharge over time when comparing those who did versus did not receive HCV treatment as a time-varying covariate. We also analyzed a subset of patients retained at least 100 days in OBOT care and evaluated whether HCV treatment during that period was associated with OBOT retention beyond 100 days. RESULTS: Of 191 HCV-infected OBOT patients, 30% initiated HCV treatment, of whom 31% received early treatment and 69% received late treatment. Median cumulative duration in OBOT was greater among those who received HCV treatment (any: 398 days, early: 284 days and late: 430 days) when compared to those who did not receive treatment (90 days). Compared to no HCV treatment, there were 83% (95% CI: 33-152%, P < 0.001), 95% (95% CI: 28%-197%, p = 0.002 and 77% (95% CI: 25-153%, p = 0.002) more cumulative days in OBOT for any, early and late HCV treatment, respectively. HCV treatment was associated with a lower relative hazard for discharge/drop-out, although results did not meet statistical significance (aHR = 0.59;95% CI: 0.34-1.00; p = 0.052). Among the subset of 84 patients retained in OBOT at least 100 days, 18 received HCV treatment during that period. Compared to those who did not receive treatment within the first 100 days, those who received treatment had 57% (95% CI: -3%-152%, p = 0.065) more subsequent days in OBOT. CONCLUSIONS: A minority of HCV-infected patients received HCV treatment after initiating OBOT treatment, but those who did had better retention. Further efforts are needed to facilitate rapid HCV treatment and evaluate whether early HCV treatment improves OBOT engagement.

Injecting practices during and after hepatitis C treatment and associations with not achieving cure among persons who inject drugs.

BACKGROUND: Persons who inject drugs (PWID) are a key population for hepatitis C virus (HCV) treatment. Study aims were to describe injection practices of PWID during HCV treatment with direct-acting antivirals (DAAs) and assess whether injection practices were associated with not achieving a sustained virologic response (SVR). METHODS: Secondary analysis of the HERO Study (ClinicalTrials.gov, NCT02824640), a pragmatic randomized trial in 8 U.S. states to evaluate the effectiveness of HCV care models among active PWID seen in opioid treatment programs and community clinics. Frequency, sharing and reuse of injecting equipment were assessed at baseline, end-of-treatment (EOT) and quarterly visits up to 60 weeks post-treatment. Generalized Estimating Equations logistic regression models with linear spline were used to compare trends in injecting behaviors during vs. post-treatment. Multivariable logistic regression models explored associations between injecting behaviors during treatment and lack of SVR. RESULTS: Among 501 participants, 27% were female, 35% were non-white, mean age was 44 (SD 11.5) years and nearly half (49%) were unhoused. At baseline, 41% reported receptive sharing of injecting equipment, declining to 16% at EOT visit. Receptive sharing of cookers, rinses, or needles/syringes during treatment was associated with a nearly 5-fold increase in not achieving SVR (adjusted odds ratio (aOR)=4.83; 95% CI: 2.26, 10.28) as was reuse of one's own needles/syringes (aOR=2.37; 95% CI: 1.11, 4.92). CONCLUSIONS: PWID in the HERO study adopted safer injecting behaviors during DAA treatment; receptive sharing of injecting equipment and reuse of one's own equipment during treatment were associated with not achieving cure.

Patient-centred models of hepatitis C treatment for people who inject drugs: a multicentre, pragmatic randomised trial.

BACKGROUND: To achieve WHO targets for the elimination of hepatitis C virus (HCV) as a public threat, an increased uptake of HCV treatment among people who inject drugs (PWID) is urgently needed. Optimal HCV co-located treatment models for PWID have not yet been identified. We aimed to compare two patient-centred models of HCV care in PWID with active drug use. METHODS: We did a pragmatic randomised controlled trial at eight US cities in eight opioid treatment programmes and 15 community health centres. PWID actively injecting within 90 days of study entry were randomly assigned (1:1) to either patient navigation or modified directly observed therapy (mDOT) using computer-generated variable block sizes of 2-6 stratified by city, clinical settings, and cirrhosis status. The randomisation code was concealed, in a centralised REDCap database platform, from all investigators and research staff except for an authorised data manager at the data coordinating centre. All participants received a fixed-dose combination tablet (sofosbuvir 400 mg plus velpatasvir 100 mg) orally once daily for 12 weeks. The primary outcome was sustained virological response (SVR; determined by chart review between 70 days and 365 days after end of treatment and if unavailable, by study blood draws), and secondary outcomes were treatment initiation, adherence (measured by electronic blister packs), and treatment completion. Analyses were conducted within the modified intention-to-treat (mITT; all who initiated treatment), intention-to-treat (all who were randomised), and per-protocol populations. This trial is registered with ClinicalTrials.gov, NCT02824640. FINDINGS: Between Sept 15, 2016, and Aug 14, 2018, 1891 individuals were screened and 1136 were excluded (213 declined to participate and 923 did not meet the eligibility criteria). We randomly assigned 755 participants to patient navigation (n=379) or mDOT (n=376). In the mITT sample of participants who were randomised and initiated treatment (n=623), 226 (74% [95% CI 69-79]) of 306 participants in the mDOT group and 236 (76% [69-79]) of 317 in the patient navigation group had an SVR, with no significant difference between the groups (adjusted odds ratio [AOR] 0·97 [95% CI 0·66-1·42]; p=0·35). In the ITT sample (n=755), 226 (60% [95% CI 55-65]) of 376 participants in the mDOT group and 236 (62% [57-67]) of 379 in the patient navigation group had an SVR (AOR 0·92 [0·68-1·25]; p=0·61) and in the per-protocol sample (n=501), 226 (91% [87-94]) of 248 participants in the mDOT group and 235 (93% [89-96]) of 253 in the patient navigation group had an SVR (AOR 0·79 [0·41-1·55]; p=0·44). 306 (81%) of 376 participants in the mDOT group and 317 (84%) of 379 participants in the patient navigation group initiated treatment (AOR 0·86 [0·58-1·26]; p=0·44) and, among those, 251 (82%) participants in the mDOT group and 264 (83%) participants in the patient navigation group completed treatment (AOR 0·90 [0·58-1·39]; p=0·63). Mean daily adherence was higher in the mDOT group (78% [95% CI 75-81]) versus the patient navigation group (73% [70-77]), with a difference of 4·7% ([1·9-7·4]; p=0·0010). 421 serious adverse events were reported (217 in the mDOT group and 204 in the patient navigation group), with the most common being hospital admission (176 in the mDOT group vs 161 in the patient navigation group). INTERPRETATION: In this trial of active PWID, both models resulted in high SVR. Although adherence was significantly higher in the mDOT group versus the patient navigation group, there was no significant difference in SVR between the groups. Increases in adherence and treatment completion were associated with an increased likelihood of SVR. These results suggest that active PWID can reach high SVRs in diverse settings with either mDOT or patient navigation support. FUNDING: Patient-Centered Outcomes Research Institute, Gilead Sciences, Quest Diagnostics, Monogram Biosciences, and OraSure Technologies.

Acceptability, feasibility, and outcomes of a clinical pilot program for video observation of methadone take-home dosing during the COVID-19 pandemic.

BACKGROUND: Methadone is one of the most utilized treatments for opioid use disorder. However, requirements for observing methadone dosing can impose barriers to patients and increase risk for respiratory illness transmission (e.g., COVID-19). Video observation of methadone dosing at home could allow opioid treatment programs (OTPs) to offer more take-home doses while ensuring patient safety through remote observation of ingestion. METHODS: Between April and August 2020, a clinical pilot program of video observation of methadone take-home dosing via smartphone was conducted within a multisite OTP agency. Participating patients completed a COVID-19 symptom screener and submitted video recordings of themselves ingesting all methadone take-home doses. Patients who followed these procedures for a two-week trial period could continue participating in the full pilot program and potentially receive more take-home doses. This retrospective observational study characterizes patient engagement and compares clinical outcomes with matched controls. RESULTS: Of 44 patients who initiated the two-week trial, 33 (75 %) were successful and continued participating in the full pilot program. Twenty full pilot participants (61 %) received increased take-home doses. Full pilot participants had more days with observed dosing over a 60-day period than matched controls (mean = 53.2 vs. 16.6 days, respectively). Clinical outcomes were similar between pilot participants and matched controls. CONCLUSIONS: Video observation of methadone take-home dosing implemented during the COVID-19 pandemic was feasible. This model has the potential to enhance safety by increasing rates of observed methadone dosing and reducing infection risks and barriers associated with relying solely on face-to-face observation of methadone dosing.

Peer providers and linkage with buprenorphine care after hospitalization: A retrospective cohort study.

Background: People with opioid use disorder (OUD) are increasingly started on buprenorphine in the hospital, yet many patients do not attend outpatient buprenorphine care after discharge. Peer providers, people in recovery themselves, are a growing part of addiction care. We examine whether patients who received a low-intensity, peer-delivered intervention during hospitalization had a greater rate of linking with outpatient buprenorphine care relative to those not seen by a peer. Methods: This was a retrospective cohort study of adults with OUD who were started on buprenorphine during hospitalization. The primary outcome was receipt of a buprenorphine prescription within 30 days of discharge. Secondary outcomes included attendance at a follow-up visit with a buprenorphine provider within 30 days and hospital readmission within 90 days. Modified Poisson regression analyses tested for differences in the rate ratios (RR) of each binary outcome for patients who were versus were not seen by a peer provider. Peer notes in the electronic health record were reviewed to characterize peer activities. Results: 111 patients met the study inclusion criteria, 31.5% of whom saw a peer provider. 55.0% received a buprenorphine prescription within 30 days of hospital discharge. Patients with versus without peer provider encounters did not significantly differ in the rates of receiving a buprenorphine prescription (RR = 1.06, 95% CI: 0.74-1.51), hospital readmission (RR = 1.45, 95% CI: 0.80-2.64), or attendance at a buprenorphine follow-up visit (RR = 1.03, 95% CI: 0.68-1.57). Peers most often listened to or shared experiences with patients (68.6% of encounters) and helped facilitate medical care (60.0% of encounters). Conclusions: There were no differences in multiple measures of buprenorphine follow-up between patients who received this low-intensity peer intervention and those who did not. There is need to investigate what elements of peer provider programs contribute to patient outcomes and what outcomes should be assessed when evaluating peer programs.

Video directly observed therapy for patients receiving office-based buprenorphine - A pilot randomized controlled trial.

BACKGROUND: We conducted a pilot study to assess feasibility of using video directly-observed therapy (DOT) for patients initiating buprenorphine to evaluate whether it is associated with better opioid use disorder (OUD) outcomes when compared to treatment-as-usual (TAU). METHODS: Pilot randomized controlled trial of adult patients with OUD initiating buprenorphine treatment (n = 78) at two sites (Seattle, WA and Boston, MA) from January 2019 to May 2020. Intervention was video DOT using a HIPAA-compliant smartphone application to record taking daily buprenorphine. Study smartphones, text reminders to upload a video, and calendar summaries of video DOT adherence were provided. Main outcomes were 1) percentage of 12 weekly urine drug tests (UDT) negative for illicit opioids and 2) engagement in treatment at week 12 (i.e., having an active prescription for buprenorphine within the last 7 days). RESULTS: Of 78 enrolled, 20 (26 %) were female; 29 (37 %) non-white; and 31 (40 %) homeless. The mean (standard deviation) percentage of doses confirmed by video was 31 % (34 %). In intention-to-treat analysis, the average percentage of weekly opioid negative UDT was 50 % (95 % CI: 40-63 %) in the intervention arm versus 64 % (95 % CI: 55-74 %) among controls; RR = 0.78 (95 % CI: 0.60-1.02, p = 0.07). Engagement at week 12 was 69 % (95 % CI: 56-86 %) v. 82 % (95 % CI: 71-95 %) in the intervention vs. TAU arms, respectively; RR = 0.84 (95 % CI: 0.65-1.10, p = 0.20). CONCLUSIONS: The video DOT intervention did not result in improvements in illicit opioid use and treatment engagement compared to TAU. The study was limited by low rates of intervention use. TRIAL REGISTRATION: ClinicalTrails.gov, NCT03779997, Registered on December 19, 2018.

Staff Attitudes toward Buprenorphine before and after Implementation of an Office-Based Opioid Treatment Program in an Urban Teaching Clinic.

PURPOSE: Improving access to buprenorphine treatment is necessary to address the national opioid use disorder (OUD) crisis. This study investigates attitudes about buprenorphine prescribing among staff at a primary care clinic and compares attitudes before and after implementation of an office-based opioid treatment (OBOT) program. METHODS: Providers and staff in an academic primary care clinic were surveyed prior to and one year following implementation of an OBOT program. Descriptive statistics, Pearson's Chi-2 tests and logistic regression models were used to compare staff and provider attitudes about use of buprenorphine for OUD and to compare attitudes before and after OBOT implementation. RESULTS: At baseline, 20% of staff indicated strong belief that buprenorphine is an effective treatment for OUD and 16% indicated strong belief that primary care providers should prescribe it. Staff appeared less likely than providers to believe strongly that buprenorphine is effective (OR 0.24, 95% CI= 0.08-.78, p = 0.02; aOR 0.28, 95% CI=.08-1.0, p = 0.05 adjusted for age, race and gender). Following implementation of an OBOT program, the percentage of staff who believed strongly in the effectiveness of buprenorphine for OUD increased from 20% to 40% (p = 0.31), and the percentage who believed that primary care providers (PCPs) should prescribe it increased from 16% to 30% (p = 0.52). CONCLUSIONS: Staff in a primary care clinic were less likely than providers to believe in the effectiveness of buprenorphine treatment or that PCPs should prescribe it for OUD. That their beliefs substantially changed after implementation of an OBOT program suggests that direct experience impacts attitudes.

Hepatitis C treatment outcomes among patients treated in co-located primary care and addiction treatment settings.

BACKGROUND: Persons with substance use disorders face major barriers to hepatitis C virus (HCV) treatment. Co-location of addiction and HCV treatment is appealing, yet there are limited data on outcomes using this model. This study evaluated HCV outcomes of patients treated with direct-acting antivirals (DAAs) by primary care providers in two sites of co-located addiction/HCV care. METHODS: The study conducted a retrospective chart review for all patients receiving DAA treatment from 2016 to 2018 at 1) a hospital-based primary care clinic with an office-based buprenorphine program, and 2) a primary care clinic within an opioid treatment program (i.e. methadone clinic). The study classified patients into 3 groups according to treatment status: buprenorphine maintenance, methadone maintenance, or neither. Descriptive analyses compared patient demographics, clinical characteristics, adherence to monitoring and treatment, and the primary outcome of sustained virologic response at 12 weeks (SVR12), defined as an undetectable HCV viral load at least 12 weeks after completing treatment. RESULTS: This study included 50 patients who initiated DAA treatment. The majority of patients were unemployed (74.0%), did not smoke tobacco (54.0%), and had psychiatric comorbidities (80.0%). Many also experienced homelessness during treatment (22.0%) and experienced previous incarceration (36.0%). Only a few had recently injected drugs (4.0%). Seven of 7 (100%) patients were treated with buprenorphine, 21 of 24 (87.5%) patients were treated with methadone, and 17 of 19 (89.5%) patients receiving no opioid addiction treatment fully completed HCV DAA treatment. When including patients with missing SVR12 data with the cohort that did not achieve cure, we observe that 44 of 50 patients (88.0%) achieved SVR12. Excluding patients missing SVR12 data, we observed that 44 of 46 patients (95.7%) achieved SVR12. CONCLUSION: Persons with substance use disorders treated with DAAs in co-located primary care and addiction treatment settings can achieve high rates of cure despite significant comorbidities and barriers. DAA treatment should be expanded to co-located HCV and addiction settings.

Acceptability and Feasibility of a Mobile Health Application for Video Directly Observed Therapy of Buprenorphine for Opioid Use Disorders in an Office-based Setting.

INTRODUCTION/BACKGROUND: Video directly observed therapy (video-DOT) through a mobile health platform may improve buprenorphine adherence and decrease diversion. This pilot study tested the acceptability and feasibility of using this technology among patients receiving buprenorphine in an office-based setting. METHODS: Participants were instructed to record videos of themselves taking buprenorphine. Data were collected from weekly in-person visits over a 4-week period; assessments included self-report of medication adherence, substance use, satisfaction with treatment and use of the application, and also urine drug testing. Open-ended questions at the final visit solicited feedback on patients' experiences using the mobile health application. RESULTS: The sample consisted of 14 patients; a majority were male (86%) and White (79%). All participants except 1 (93%) were able to use the application successfully to upload videos. Among those who successfully used the application, the percentage of daily videos uploaded per participant ranged from 18% to 96%; on average, daily videos were submitted by participants 72% of the time. Most participants (10/14; 71%) reported being "very satisfied" with the application; of the remaining 4 participants, 2 were "satisfied" and 2 were "neutral." Participants reported liking the accountability and structure of the application provided and its ease of use. Negative feedback included minor discomfort at viewing one's self during recording and the time required. CONCLUSIONS: Based on these results, use of a mobile health application for video-DOT of buprenorphine appears feasible and acceptable for patients who are treated in an office-based setting. Further research is needed to test whether use of such an application can improve treatment delivery and health outcomes.