A Randomized Trial Evaluating Acceptance and Commitment Therapy and Smart Phone Care Management Application to Augment Buprenorphine Therapy for Opioid Use and Chronic Pain.

There is high comorbidity of opioid use disorder (OUD) and chronic pain (CP), which is often addressed by prescribing buprenorphine (BUP). While BUP is effective in preventing overdose, it does not address the psychological aspects of OUD and CP comorbidity and treatment retention rates are as low as 50%. The Virtual Opioid use disorder Integrated Chronic Pain Treatment (VOICE) study (NCT05039554) is a novel effectiveness-implementation trial to test a 12-week virtual group Acceptance and Commitment Therapy (ACT) protocol and a care management smartphone application (app; Valera Health) on pain and opioid use in patients with OUD and CP receiving BUP. Using a 2 × 2 factorial design, participants (expected N = 280) are randomized into: ACT, Valera app, ACT + Valera, or Treatment as Usual arm. This study is taking place in the Bronx, NY, a racially/ethnically diverse community that faces numerous socioeconomic stressors and is one of the nation's epicenters of the opioid epidemic. We created a culturally responsive ACT group protocol, and Valera psychoeducational material. Outcome measures include NIH HEAL Common Data Elements and ACT and Valera-specific measures. We are conducting a novel 2 × 2 trial investigating augmenting BUP treatment with ACT and Valera, with the goal that improved mental health and access to care will result in decreased and opioid use and pain interference.

Hepatitis C Virus Reinfection Among People Who Inject Drugs: Long-Term Follow-Up of the HERO Study.

IMPORTANCE: Hepatitis C virus (HCV) reinfection after curative treatment remains a concern for people who inject drugs. OBJECTIVE: To assess the incidence of HCV reinfection and associated risk factors. DESIGN, SETTING, AND PARTICIPANTS: This cohort study is a secondary analysis of a randomized clinical trial that was conducted across opioid treatment programs and community health centers in the US between September 2016 and August 2018. The current analyses were performed in March 2022. People who inject drugs who achieved sustained virologic response (SVR) were followed for up to 42 months. Exposure: Patients were randomly assigned to receive modified directly observed therapy or patient navigation. MAIN OUTCOMES AND MEASURES: The primary outcome was rate of HCV reinfection. Change in reinfection rates over time was assessed using a Poisson regression model. RESULTS: A total of 415 participants (mean [SD] age, 44.7 [11.5] years; 302 male [72.8%]) achieved a SVR and had 1 or more post-SVR assessments for HCV RNA. Overall, 302 (72.8%) reported recent injection drug use, 192 (46.3%) were living in unstable housing, and 313 (75.4%) had received recent methadone or buprenorphine for opioid use disorder. The overall reinfection rate was 11.4 per 100 person-years at risk (95% CI, 8.7-14.7 per 100 person-years at risk) over 518 person-years of follow-up. Reinfection rates varied significantly across sites, ranging from 2.9 per 100 person-years at risk (95% CI, 0.1-16.3 per 100 person-years) to 25.2 per 100 person-years at risk (95% CI, 15.6-38.5 per 100 person-years at risk) (P = .006). There was a significant decrease in incident reinfection with increasing post-SVR follow-up (weeks 0-24, 15.5 per 100 person-years; 95% CI, 10.3-22.3 per 100 person-years; weeks 73-144, 4.3 per 100 person-years; 95% CI, 0.9-12.5 per 100 person-years; P = .008). Reinfection rates were lower for participants aged 40 years or older than for younger participants (adjusted incidence rate ratio, 0.32; 95% CI, 0.18-0.57) and for participants for whom methamphetamine was not detected in urinary drug screening compared with participants for whom methamphetamine was detected (adjusted incidence rate ratio, 0.41; 95% CI, 0.21-0.82). Participants who reported injection drug use within the preceding 3 months had higher risk of reinfection than those who did not have recent injection drug use (adjusted incidence rate ratio, 3.33; 95% CI, 1.86-5.97). CONCLUSIONS AND RELEVANCE: In this cohort study of people who injected drugs and were treated for HCV infection in community settings, reinfection was high in the period immediately after SVR but decreased significantly over time. These findings highlight the importance of early intervention to prevent reinfection. Trial Registration: ClinicalTrials.gov Identifier: NCT02824640.

Distrust in the Health Care System and Adherence to Direct-Acting Antiviral Therapy among People with Hepatitis C Virus Who Inject Drugs.

This study is a secondary analysis of a randomized clinical trial (October 2013-April 2017) involving 150 People Who Inject Drugs (PWIDs) with hepatitis C virus (HCV) seen in opioid agonist treatment programs in the Bronx, New York, and investigates the impact of distrust in the healthcare system on adherence to Direct-Acting Antivirals (DAAs) HCV treatment therapy among PWIDs. The distrust was scaled on a 9-item instrument and the adherence to DAA medications was measured using electronic blister packs. This study demonstrated a significant inverse relationship between levels of distrust and medication adherence: 71.8 ± 2.2% (se) vs. 77.9 ± 1.8%, p = 0.024 between participants with higher and lower distrust levels. Despite the absence of significant association of distrust with sociodemographic or substance use characteristics, these findings suggest that building trust within the healthcare system is paramount for improving adherence to DAAs among PWIDs. The results call for a healthcare approach that emphasizes trust-building through patient-centered care, sensitivity training, peer support, and health system reform to effectively address the treatment needs of this marginalized population.

Effect of self-efficacy among persons who inject drugs treated with direct-acting antivirals on Hepatitis C treatment initiation, duration, completion, adherence, and cure.

BACKGROUND: Self-efficacy, a patient-level factor, has been shown to facilitate patient engagement in treatment and optimize treatment-related outcomes in various health contexts. Research on interventions supporting hepatitis C virus (HCV) direct-acting antiviral (DAA) treatment uptake and adherence among persons who inject drugs (PWID) is needed, but whether self-efficacy factors influence DAA treatment cascade outcomes in this population has been less studied. METHODS: Using the HERO study data, we analyzed a subset of participants with any general health self-efficacy data (n=708) measured at baseline and end-of-treatment time points using a 5-items instrument (facets: 'goal setting', 'goal attainment', 'having a positive effect', 'being in control', and 'working to improve'). The cascade outcomes included DAA treatment initiation, duration, adherence, completion, and sustained virologic response (SVR). The effect of baseline and change (Δ) scores for composite and item-level self-efficacy on the cascade outcomes was assessed using logistic regression and generalized linear models. RESULTS: Higher baseline composite self-efficacy [adjusted odds ratio (95 % confidence interval) =1.57 (1.07, 2.29)], 'goal attainment' [1.31 (1.03, 1.67)] and 'having a positive effect' [1.33 (1.03, 1.74)] were associated with greater likelihood of treatment initiation. 'Δ Goal attainment' was significantly associated with SVR [1.63 (1.04, 2.53)]. 'Δ Being in control' and 'Δ working to improve' were associated with treatment adherence and duration, respectively. CONCLUSIONS: General health self-efficacy positively influences DAA treatment initiation among PWID. 'Goal attainment' facilitates the achievement of DAA treatment-related outcomes. Further studies should assess the effect of self-efficacy related to performing healthcare tasks specific to DAAs on the treatment-related outcomes.

Overreporting of adherence to hepatitis C direct-acting antiviral therapy and sustained virologic response among people who inject drugs in the HERO study.

BACKGROUND: Self-reported adherence to direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV) among persons who inject drugs (PWID) is often an overreport of objectively measured adherence. The association of such overreporting with sustained virologic response (SVR) is understudied. This study among PWID aimed to determine a threshold of overreporting adherence that optimally predicts lower SVR rates, and to explore correlates of the optimal overreporting threshold. METHODS: This study analyzed per-protocol data of participants with adherence data (N = 493) from the HERO (Hepatitis C Real Options) study. Self-reported and objective adherence to a 12-week DAA regimen were measured using visual analogue scales and electronic blister packs, respectively. The difference (Δ) between self-reported and objectively measured adherence was calculated. We used the Youden index based on receiver operating characteristic (ROC) curve analysis to identify an optimal threshold of overreporting for predicting lower SVR rates. Factors associated with the optimal threshold of overreporting were identified by comparing baseline characteristics between participants at/above versus those below the threshold. RESULTS: The self-reported, objective, and Δ adherence averages were 95.1% (SD = 8.9), 75.9% (SD = 16.3), and 19.2% (SD = 15.2), respectively. The ≥ 25% overreporting threshold was determined to be optimal. The SVR rate was lower for ≥ 25% vs. < 25% overreporting (86.7% vs. 95.8%, p <.001). The factors associated with ≥ 25% Δ adherence were unemployment; higher number of days and times/day of injecting drugs; higher proportion of positive urine drug screening for amphetamine, methamphetamine, and oxycodone, and negative urine screening for THC (tetrahydrocannabinol)/cannabis. CONCLUSIONS: Self-reported DAA adherence was significantly greater than objectively measured adherence among PWID by 19.2%. Having ≥ 25% overreported adherence was associated with optimal prediction of lower SVR rates. PWID with risk factors for high overreporting may need to be more intensively managed to promote actual adherence.

Optimal hepatitis C treatment adherence patterns and sustained virologic response among people who inject drugs: The HERO study.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are highly effective for treating HCV infection even among people who inject drugs (PWID). Yet, little is known about patients' adherence patterns and their association with sustained virologic response (SVR) rates. We aimed to summarize various adherence patterns and determine their associations with SVR. METHODS: Electronic blister packs were used to measure daily adherence to once-a-day sofosbuvir/velpatasvir during the 12-week treatment period among active PWIDs. Blister pack data were available for 496 participants who initiated DAAs for whom SVR status was known. Adherence was summarized in multiple patterns, such as total adherent days, consecutive missed days, and early discontinuations. Thresholds for adherence patterns associated with >90% SVR rates were also determined. RESULTS: The overall SVR rate was 92.7%, with a median adherence rate of 75%. All adherence patterns indicating greater adherence were significantly associated with achieving SVR. Participant groups with ≥50% (>42/84) adherent days or <26 consecutive missed days achieved an SVR rate of >90%. Greater total adherent days during 9-12 weeks and no early discontinuation were significantly associated with higher SVR rates only in those with <50% adherence. Participants with first month discontinuation and ≥2 weeks of treatment interruption had low SVR rates, 25% and 85%, respectively. However, greater adherent days were significantly associated with SVR (adjusted odds ratio 1.10; 95% CI 1.04-1.16; p <0.001) even among participants with ≥14 consecutive missed days. CONCLUSIONS: High SVR rates can be achieved in the PWID population despite suboptimal adherence. Encouraging patients to take as much medication as possible, with <2 weeks consecutive missed days and without early discontinuation, was found to be important for achieving SVR. IMPACT AND IMPLICATIONS: People who inject drugs can be cured of HCV in >90% of cases, even with relatively low adherence to direct-acting antivirals, but early discontinuations and long treatment interruptions can significantly reduce the likelihood of achieving cure. Clinicians should encourage people who inject drugs who are living with HCV to adhere daily to direct-acting antivirals as consistently as possible, but if any days are interrupted, to continue and complete treatment. These results from the HERO study are important for patients living with HCV, clinicians, experts writing clinical guidelines, and payers. CLINICAL TRIAL NUMBER: NCT02824640.

Self-reported and measured adherence to hepatitis C direct-acting antiviral therapy and sustained virologic response among people who inject drugs: The HERO study.

BACKGROUND: Objective adherence measures, such as electronic blister pack (BP), for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment have high accuracy, but their use is limited in real practice settings. We examined the association of self-reported adherence using a visual analogue scale (VAS) with objective BP adherence and sustained virologic response (SVR) among people who inject drugs. METHODS: We conducted secondary analyses using a subset of participants (N = 493) from the per-protocol sample of the HERO study, a pragmatic randomized trial of HCV treatment interventions that used both VAS and BP to measure adherence to a 12-week sofosbuvir/velpatasvir DAA regimen. Multivariable mixed-effects regression models tested the association of self-report adherence level with longitudinal weekly objective adherence. Multivariable logistic regression tested the association of self-report adherence with SVR. RESULTS: The average VAS and BP adherences were 95.1 % (SD = 8.9 %) and 76.0 % (16.0 %), respectively, and the proportion of the participants achieving SVR was 92.9 %. The estimated adjusted mean objective adherence was significantly different (-16 %; 95 % CI: -22 %, -11 %, p < .001) between participants with 100 % and <80 % VAS adherence. The likelihood of SVR was significantly lower for those with <80 % VAS adherence [adjusted OR = 0.07; 95 % CI: 0.02, 0.24; p < .001] compared to those with 100 %. CONCLUSION: Self-reported adherence overestimated objective adherence. However, higher self-report adherence was significantly associated with higher objective adherence. Also, self-reported adherence ≥80 % was significantly associated with SVR. Thus, the self-report measure has utility as a monitoring tool for adherence during DAA treatment.

Shame and stigma in association with the HCV cascade to cure among people who inject drugs.

BACKGROUND: Psycho-social experiences including shame and experienced and internalized stigma have been associated with substance use, HCV infection, and reluctance to disclose HCV status and pursue treatment. These psycho-social barriers have been examined independently for many chronic diseases, including HCV, but to our knowledge have not been quantitatively explored in a large multi-site US-based sample of people who inject drugs (PWID) in HCV treatment. METHODS: We examine baseline relationships with HCV-stigma and engagement across the HCV treatment cascade as well as baseline and longitudinal relationships between shame and engagement across the HCV treatment cascade including treatment initiation, adherence, completion, and sustained virologic response (SVR) among a multi-site sample of PWID with HCV, where N=755 were randomized to the pragmatic trial comparing HCV treatment outcomes in modified directly observed treatment (mDOT) or patient navigation, and N=623 initiated treatment. RESULTS: While cross-sectional assessments of shame and HCV-stigma were not associated with engagement across the HCV treatment cascade, those whose shame scores decreased compared to those who reported consistently high and increasing levels of shame were significantly more likely to complete HCV treatment (aOR=5.29; 95%CI: 1.56,18.00) and achieve SVR (aOR=6.32; 95%CI: 1.61, 24.87). CONCLUSION: Results underscore the relationships between lower levels of shame and health-related behavior and treatment outcomes among PWID and suggest SVR achievement may contribute to reductions in shame or that reductions in shame may contribute to continued treatment and thus SVR.

Reduction in Depressive Symptoms in People who Inject Drugs who Are Cured of Hepatitis C Virus Infection: The HERO Study.

Background: Depressive symptoms are prevalent among people who inject drugs (PWID) and people with hepatitis C virus (HCV). We examined changes in depressive symptoms among HCV-infected PWID following direct-acting antiviral treatments to evaluate whether these changes differed by history of depressive symptoms, substance use, or HCV treatment outcome. Methods: We conducted a secondary analysis of the HERO Study (NCT02824640), a pragmatic randomized clinical trial among PWID, to test the effectiveness of HCV care models. Depressive symptoms (primary outcome) were measured using the Patient Health Questionnaire (PHQ-9) at baseline, end of treatment (EOT), and at follow-up 12 and 24 weeks after EOT. Sustained virologic response (SVR) was defined as undetectable HCV RNA at ≥12 weeks following EOT. Baseline drug use was defined as having a positive urine screening test for amphetamine, methamphetamine, benzodiazepine, cocaine, cannabis, opiate, or oxycodone. Results: The sample (n = 498) was 72.3% male, 64.2% White, and on average 43.9 years old. In patients who achieved SVR (F(3432) = 4.58; P = .004) and those with drug use at baseline (F(3478) = 5.11; P < .01), PHQ-9 scores significantly declined over time, with scores lower at EOT and both follow-ups as compared with baseline. Mean PHQ-9 scores at EOT and follow-ups were significantly lower than at baseline, except for those with no depression or mild depression at baseline. Conclusions: This study showed that HCV treatment in PWID is associated with sustained declines in depression up to 24 weeks post-treatment among those who achieve SVR and that drug use does not interfere with improvement in depressive symptoms.

A Video-Observed Treatment Strategy to Improve Adherence to Treatment Among Persons Who Inject Drugs Infected With Hepatitis C Virus: Qualitative Study of Stakeholder Perceptions and Experiences.

BACKGROUND: Direct-acting antiviral medications have the potential to eliminate the hepatitis C virus (HCV) epidemic among people who inject drugs; yet, suboptimal adherence remains a barrier. Directly observed treatment (DOT), an effective strategy for optimizing adherence, has been frequently implemented in opioid treatment programs but less commonly in community health settings due to the heavy burden of daily visits. An alternative is video-observed therapy (VOT), which uses mobile health technology to monitor adherence. VOT has not been widely studied among people who inject drugs with HCV. OBJECTIVE: This qualitative study, part of a larger implementation evaluation, investigates stakeholder perceptions and experiences with VOT in Project HERO (Hepatitis C Real Outcomes), a multisite pragmatic trial testing treatment delivery models for people who inject drugs with HCV. Our goal was to understand the potential barriers and facilitators to the implementation of the VOT technology. METHODS: Qualitative interviews were conducted with 27 Project HERO study staff and 7 patients. Interviews focused on perceptions and experiences with the VOT app and barriers and facilitators to implementation. Team meeting minutes over the first 2 years of the project were transcribed. A coding system was developed and applied to the data. We summarized thematic data and compared participant perceptions to generate a close understanding of the data. RESULTS: Frequent barriers to VOT included mechanical failure, stolen or lost phones, and a steep learning curve for participants and study staff. In sites with older and less technically skilled participants, staff found it difficult to implement the VOT app. Research staff found that the routine monitoring of app use led to closer engagement with participants. This was both a benefit and a potential threat to the validity of this pragmatic trial. Patient participants reported mixed experiences. CONCLUSIONS: VOT may be a useful alternative to DOT for some patients, but it may not be feasible for all. Significant staff involvement may be required.

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.

The experience of re-infection among people who inject drugs successfully treated for hepatitis C.

INTRODUCTION: Highly effective direct-acting antiviral (DAA) agents have changed the landscape of hepatitis C virus infection (HCV) treatment and have become more available to people who inject drugs (PWID) over the past several years. Although many achieve a sustained virologic response (SVR), a small proportion will become re-infected. This study examined experiences of re-infection among participants in Project HERO, a large multi-site treatment trial designed to test alternative treatment delivery models for DAAs. METHODS: Study staff conducted qualitative interviews with twenty-three HERO participants who experienced reinfection following successful treatment for HCV. Interviews focused on life circumstances and experiences with treatment/re-infection. We conducted a thematic analysis, followed by a narrative analysis. RESULTS: Participants described challenging life circumstances. The initial experience of cure was joyful, leading participants to feel that they had escaped a defiled, stigmatized identity. Re-infection was very painful. Feelings of shame were common. Participants with fully developed narratives of re-infection described both a strong emotional response as well as a plan for avoiding re-infection during retreatment. Participants who lack such stories showed signs of hopelessness and apathy. CONCLUSION: Though the promise of personal transformation through SVR may be motivating for patients, clinicians should be cautious about how they describe the "cure" when educating patients about HCV treatment. Patients should be encouraged to avoid stigmatizing, dichotomizing language of the self, including terms such as "dirty" and "clean." In acknowledging the benefits of HCV cure, clinicians should emphasize that re-infection does not mean failed treatment; and that current treatment guidelines support retreatment of re-infected PWID.

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.

Reinfection and Risk Behaviors After Treatment of Hepatitis C Virus Infection in Persons Receiving Opioid Agonist Therapy : A Cohort Study.

BACKGROUND: Hepatitis C virus (HCV) reinfection after successful treatment may reduce the benefits of cure among people who inject drugs. OBJECTIVE: To evaluate the rate of HCV reinfection for 3 years after successful treatment among people receiving opioid agonist therapy (OAT). DESIGN: A 3-year, long-term, extension study of persons enrolled in the CO-STAR (Hepatitis C Patients on Opioid Substitution Therapy Antiviral Response) study (ClinicalTrials.gov: NCT02105688). SETTING: 55 clinical trial sites in 13 countries. PATIENTS: Aged 18 years and older with chronic HCV infection with genotypes 1, 4, or 6 receiving stable OAT. INTERVENTION: No treatments were administered. MEASUREMENTS: Serum samples were assessed for HCV reinfection. Urine drug screening was performed. RESULTS: Among 296 participants who received treatment, 286 were evaluable for reinfection and 199 were enrolled in the long-term extension study. The rate of HCV reinfection was 1.7 [95% CI, 0.8 to 3.0] per 100 person-years; 604 person-years of follow-up). A higher rate of reinfection was seen among people with recent injecting drug use (1.9 [95% CI, 0.5 to 4.8] per 100 person-years; 212 person-years). Ongoing drug use and injecting drug use were reported by 59% and 21% of participants, respectively, at the 6-month follow-up visit and remained stable during 3 years of follow-up. LIMITATIONS: Participants were required to be 80% adherent to OAT at baseline and may represent a population with higher stability and lower risk for HCV reinfection. Rate of reinfection may be underestimated because all participants did not continue in the long-term extension study; whether participants who discontinued were at higher risk for reinfection is unknown. CONCLUSION: Reinfection with HCV was low but was highest in the first 24 weeks after treatment completion and among people with ongoing injecting drug use and needle-syringe sharing. PRIMARY FUNDING SOURCE: Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.

Changes in alcohol use during hepatitis C treatment in persons who inject drugs.

People who inject drugs (PWID) are a vulnerable population at high risk for acquiring hepatitis C virus (HCV) and frequently suffer from comorbid alcohol use. This study examines the characteristics and correlates of alcohol use among study participants, the association between alcohol consumption and sustained virologic response (SVR) in patients receiving HCV treatment, changes in drinking behaviours during HCV treatment and associations of drinking over time with specific models of HCV treatment. Participants were 150 PWID with HCV who were receiving opioid agonist therapy (OAT) and enrolled in a randomized clinical trial exploring the effectiveness of three models of care for HCV treatment. The addiction severity index was the primary measure of alcohol consumption. Days of alcohol intake were evaluated longitudinally and across three treatment groups. At baseline, 31% (47/150) reported having at least one drink in the last 30 days including 24% (36/150) who reported drinking to intoxication in the last 30 days. There was no difference in SVR rates between groups. There was a significant decrease in overall days of drinking from baseline (7.78 ± 7.86) to follow-up at Week 24 (5.78 ± 8.83) (p = 0.041), but there were no significant changes among those who drank to intoxication; modified directly observed therapy (mDOT) was the only group with a significant decline in days of alcohol consumption (p = 0.041). In this cohort of PWID on OAT, baseline alcohol consumption did not affect SVR rates. HCV treatment was overall associated with decreased alcohol consumption. In particular, mDOT was associated with decreased alcohol consumption. Given the additive effect of alcohol and HCV on the development of cirrhosis, studies should be done to investigate the complimentary effects of the mDOT model of care on alcohol cessation.

Relationship between depressive symptoms and adherence to direct-acting antivirals: Implications for Hepatitis C treatment among people who inject drugs on medications for opioid use disorder.

BACKGROUND: Interferon-based regimens exacerbated depressive symptoms, which interfered with treating hepatitis C virus (HCV) among people who inject drugs (PWID). Direct-acting antivirals (DAA) are not associated with worsening depressive symptoms; however, the impact of depressive symptoms on adherence remains little known. We examined the association between depressive symptoms and adherence to DAA among HCV-infected PWID. A secondary aim was to identify the optimal cut-off for major depressive disorder for this population. METHODS: Participants were 150 HCV-infected PWID on maintenance treatment enrolled in a randomized clinical trial testing three HCV care models. Severity of depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II) at baseline and every 4 weeks during treatment. Current major depressive disorder at baseline was diagnosed by the Mini-International Neuropsychiatric Interview. Adherence was measured during treatment (weeks 1-12) using electronic blister packs RESULTS: BDI-II scores ≥ 18 were identified as the optimal threshold for diagnosing major depressive disorder. Participants with BDI scores ≥ 18 at baseline had significantly lower adherence rates at weeks 1-4 of treatment compared to those with BDI scores < 18 (b = -0.23, 95% CI: 0.45-0.01, p = 0.044), but not in any other time intervals (weeks 5-8, b = -0.03, 95% CI: -0.32, 0.26, p = 0.825; weeks 9-12, b = -0.33, 95% CI -0.70, 0.02, p = 0.066). CONCLUSIONS: Elevated depressive symptoms were associated with lower adherence to DAA only during the first 4 weeks of HCV treatment. Neither severe depressive symptoms nor major depressive disorder appears to be a barrier to DAA adherence among PWID.

Onsite buprenorphine inductions at harm reduction agencies to increase treatment engagement and reduce HIV risk: Design and rationale.

BACKGROUND: Despite dramatic increases in opioid use disorder (OUD) and overdose deaths, the U.S. has been unable to consistently deliver OUD treatment to those who need it. Syringe services programs (SSPs) can engage an out-of-treatment population of people with OUD that has elevated overdose risk. Buprenorphine treatment is safe and effective, and US regulations allow for prescribing from diverse locations, including SSPs. This study's objective is to test buprenorphine treatment initiation at SSPs. We hypothesize that offering onsite buprenorphine treatment initiation will improve OUD treatment engagement without reducing buprenorphine treatment effectiveness or safety. METHODS: We will recruit 250 out-of-treatment SSP participants with OUD in a large urban area. Participants will be randomized to onsite buprenorphine treatment initiation or enhanced referral. Over 2 weeks, participants in the onsite treatment arm will see a buprenorphine provider twice at the SSP, receive weekly medication packs, and then their care will be transferred to a community health center for treatment continuation. In the control arm, within one week, participants will receive an appointment at the same community health center as in the intervention arm for buprenorphine initiation and continuation. Participants will be assessed with urine drug tests, questionnaires, and medical record review. The primary outcome will be engagement in buprenorphine treatment at 30 days. Secondary outcomes include buprenorphine diversion, opioid-free urine drug tests, and intervention cost-effectiveness. DISCUSSION: Our study will contribute to the growing literature on SSPs as a conduit to OUD treatment. SSPs hold promise to deliver needed care to people with OUD.

Low-threshold Buprenorphine Treatment in a Syringe Services Program: Program Description and Outcomes.

OBJECTIVES: Low-threshold buprenorphine treatment aims to reduce barriers to evidence-based opioid use disorder treatment. We aimed to describe the treatment philosophy, practices, and outcomes of a low-threshold syringe services program (SSP)-based buprenorphine program developed through an SSP-academic medical center partnership. METHODS: We included all SSP participants who received 1 or more buprenorphine prescription from Feb 5, 2019 to October 9, 2020. We collected data on patient characteristics, substance use, buprenorphine prescriptions, and urine drug tests (UDTs). We evaluated buprenorphine treatment retention using prescription data and buprenorphine adherence using UDTs. We used 2 retention definitions: (1) percentage of patients with buprenorphine prescriptions at 30, 90, and 180 days; and (2) total percentage of days "covered" with buprenorphine prescriptions through 180 days. RESULTS: One-hundred and eighteen patients received 1 or more buprenorphine prescriptions. Patients were largely middle-aged (mean age 44, standard deviation 11), male (68%), Hispanic (31%) or Non-Hispanic Black (32%), with heroin (90%) and crack/cocaine (62%) use, and injection drug use (59%). Retention was 62%, 43%, and 31% at 30, 90, and 180 days, respectively. The median percentage of days covered with buprenorphine prescriptions through 180 days was 43% (interquartile range 8%-92%). Of the 82 patients who completed 2 or more UDTs, the median percentage of buprenorphine-positive UDTs was 71% (interquartile range 40%-100%). CONCLUSIONS: In an SSP-based low-threshold buprenorphine treatment program, approximately one-third of patients continued buprenorphine treatment for 180 days or more, and buprenorphine adherence was high. SSPs can be a pathway to buprenorphine treatment for patients at high risk for opioid-related harms.

HIV And HCV adherence and treatment outcomes among people who inject drugs receiving opioid agonist therapy.

Among people who inject drugs (PWID), 60% have HCV and 50-90% of HIV-infected PWID are co-infected with HCV. Data comparing adherence to direct-acting antiviral (DAA) therapy among HCV mono-infected and HIV/HCV co-infected PWID is limited. The impact of HCV treatment initiation on HIV antiretroviral therapy (ART) adherence is also poorly understood. We assessed DAA adherence in HCV mono-infected and HIV/HCV co-infected PWID and examined changes in ART adherence and HIV outcomes following HCV treatment. Study was conducted in three Medication for Opioid use Disorder (MOUD) programs in Bronx, New York. HCV treatment adherence was measured using electronic blister packs. 2-week DAA adherence rates were compared and controlled for study arm, psychiatric illness and alcohol intoxication within the past 30 days. ART adherence was measured using participant self-report and dichotomized to "excellent" or "other". ART adherence, CD4 count, and HIV viral load were identified six months prior to, during, and six months after HCV treatment. Statistical significance was assessed with mixed-effects regression linear or logistic models. Overall DAA adherence rates among HCV mono-infected and HIV/HCV co-infected PWID were 74% (95% CI=71-78%) and 76% (95%CI=70-83%), respectively (p=.55). There were no significant changes in ART adherence, CD4 counts, or HIV viral loads prior to, during, or after HCV treatment. This is the first study assessing the impact of DAA therapy on ART adherence and HIV treatment outcomes among PWID. It is one of the first to compare DAA adherence among HCV and HIV/HCV co-infected PWID. Our data demonstrate no significant difference in DAA adherence and no significant impact of HCV treatment on ART adherence or HIV outcomes.