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.

Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection.

BACKGROUND: A safe and effective vaccine to prevent chronic hepatitis C virus (HCV) infection is a critical component of efforts to eliminate the disease. METHODS: In this phase 1-2 randomized, double-blind, placebo-controlled trial, we evaluated a recombinant chimpanzee adenovirus 3 vector priming vaccination followed by a recombinant modified vaccinia Ankara boost; both vaccines encode HCV nonstructural proteins. Adults who were considered to be at risk for HCV infection on the basis of a history of recent injection drug use were randomly assigned (in a 1:1 ratio) to receive vaccine or placebo on days 0 and 56. Vaccine-related serious adverse events, severe local or systemic adverse events, and laboratory adverse events were the primary safety end points. The primary efficacy end point was chronic HCV infection, defined as persistent viremia for 6 months. RESULTS: A total of 548 participants underwent randomization, with 274 assigned to each group. There was no significant difference in the incidence of chronic HCV infection between the groups. In the per-protocol population, chronic HCV infection developed in 14 participants in each group (hazard ratio [vaccine vs. placebo], 1.53; 95% confidence interval [CI], 0.66 to 3.55; vaccine efficacy, -53%; 95% CI, -255 to 34). In the modified intention-to-treat population, chronic HCV infection developed in 19 participants in the vaccine group and 17 in placebo group (hazard ratio, 1.66; 95% CI, 0.79 to 3.50; vaccine efficacy, -66%; 95% CI, -250 to 21). The geometric mean peak HCV RNA level after infection differed between the vaccine group and the placebo group (152.51×103 IU per milliliter and 1804.93×103 IU per milliliter, respectively). T-cell responses to HCV were detected in 78% of the participants in the vaccine group. The percentages of participants with serious adverse events were similar in the two groups. CONCLUSIONS: In this trial, the HCV vaccine regimen did not cause serious adverse events, produced HCV-specific T-cell responses, and lowered the peak HCV RNA level, but it did not prevent chronic HCV infection. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT01436357.).

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.

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.

Meeting people where they are: implementing hospital-based substance use harm reduction.

BACKGROUND: Hospital-based addiction care focuses on assessing and diagnosing substance use disorders, managing withdrawal, and initiating medications for addiction treatment. Hospital harm reduction is generally limited to prescribing naloxone. Hospitals can better serve individuals with substance use disorders by incorporating harm reduction education and equipment provision as essential addiction care. We describe the implementation of a hospital intervention that provides harm reduction education and equipment (e.g., syringes, pipes, and fentanyl test strips) to patients via an addiction consult team in an urban, safety-net hospital. METHODS: We performed a needs assessment to determine patient harm reduction needs. We partnered with a community-based organization who provided us harm reduction equipment and training. We engaged executive, regulatory, and nursing leadership to obtain support. After ensuring regulatory compliance, training our team, and developing a workflow, we implemented this harm reduction program that provides education and equipment to individuals whose substance use goals do not include abstinence. RESULTS: During a 12-month period we provided 195 individuals harm reduction kits. CONCLUSIONS: This intervention allowed us to advance hospital-based addiction care, better educate and engage patients, staff, and clinicians, and reduce stigma. By establishing a community harm reduction partner, obtaining support from hospital leadership, and incorporating feedback from staff, clinicians, and patients, we successfully implemented harm reduction education and equipment provision in a hospital setting as part of evidence-based addiction care. TRIAL REGISTRATION: Commentary, none.

Dismantling racism against Black, Indigenous, and people of color across the substance use continuum: A position statement of the association for multidisciplinary education and research in substance use and addiction.

The Association for Multidisciplinary Education and Research in Substance Use and Addiction (AMERSA) acknowledges that racism profoundly affects persons who use alcohol and other drugs. Racism's deadly effects compounded with other social determinants of health result in a cascade of negative impacts. The AMERSA Board of Directors (BOD) proposes an initial set of strategies to promote diversity, equity, and inclusion using a framework that speaks to four key AMERSA experiences: engagement, education, mentorship, and leadership. Through these strategies, AMERSA commits to promoting equity and inclusion to dismantle the individual, institutional, and structural racism that has permeated the United States for centuries.

Barriers and facilitators to recruitment and enrollment of HIV-infected individuals with opioid use disorder in a clinical trial.

BACKGROUND: The CTN-0067 CHOICES trial tests implementation of extended-release naltrexone (XR-NTX) versus treatment-as-usual (TAU) for opioid use disorders (OUD) in HIV clinics to improve HIV viral suppression. The study team investigated recruitment strategies to elucidate the barriers and facilitators to recruitment and enrollment in the study. MAIN TEXT: Methods: Semi-structured, in-depth, digitally recorded interviews were completed with study recruitment-related staff and medical providers (n = 26) from six participating HIV clinics in the fall of 2018. Interviews probed 1) factors that might prevent prospective participants from engaging in study recruitment and enrollment procedures and 2) strategies used by study staff that encourage eligible patient participation. Interviews were transcribed and thematically analyzed using a content analysis approach. RESULTS: All respondents reported that barriers to recruitment and enrollment included challenging patient social and structural factors (e.g., homelessness or living environments with high substance use, criminal justice involvement), difficulty locating patients with unsuppressed HIV viral load and OUD within the HIV clinic, time-consuming study enrollment processes, and stigma around HIV and OUD which inhibited treatment seeking. Some respondents observed that distrust of research and researchers impeded recruitment activities in the community. A specific medication-related barrier was patient fear of opioid abstinence required prior to XR-NTX induction. Facilitators of recruitment included use of trusted peer outreach/recruitment workers in the community, hospitalizations that offered windows of opportunities for screening and XR-NTX induction, providing participant transportation, and partnerships with harm reduction organizations for referrals. CONCLUSIONS: Though study personnel encountered barriers to recruitment in the CHOICES study, persons with untreated HIV and OUD can be enrolled in multisite clinical trials by using enhanced recruitment strategies that extend outside of the HIV clinic. Employing peer outreach workers and collaborating with syringe service programs may be especially helpful in facilitating recruitment and merit inclusion in similar study protocols.

Continued Transmission of HIV Among Young Adults Who Inject Drugs in San Francisco: Still Room for Improvement.

We measured HIV incidence rate, trend and risk factors in 564 HIV-negative young people (< 30 years) who inject drugs (PWID) in San Francisco between 2000 and 2014. HIV incidence was 0.93/100 person-years (PY; 95% CI 0.50, 1.73). Incidence varied between 0.62/100 PY in 2000-2002 and 1.06/100 PY in 2012-2014 (P for trend = 1.0). HIV incidence varied significantly (P < 0.01) by race/ethnicity: among Hispanics it was 8.19/100 PY (95% CI 3.41, 19.68), African-Americans 4.59/100 PY (95% CI 1.15, 18.37), and Whites 0.26/100 PY (95% CI 0.06, 1.03). Male participants who reported sex with men (MSM) had higher HIV incidence (2.63/100 PY; 95% CI 1.31, 5.25) compared to males who did not report MSM (0.50/100 PY; 95% CI 0.12, 1.99) (P = 0.01). Despite an overall stable HIV incidence trend, incidence was elevated among African-American and Hispanic PWID, and men who have sex with men. Addressing prevention needs in these key populations is critical for the goal of eliminating HIV transmission.

2017 HIVMA of IDSA Clinical Practice Guideline for the Management of Chronic Pain in Patients Living With HIV.

Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population.It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

2017 HIV Medicine Association of Infectious Diseases Society of America Clinical Practice Guideline for the Management of Chronic Pain in Patients Living With Human Immunodeficiency Virus.

Pain has always been an important part of human immunodeficiency virus (HIV) disease and its experience for patients. In this guideline, we review the types of chronic pain commonly seen among persons living with HIV (PLWH) and review the limited evidence base for treatment of chronic noncancer pain in this population. We also review the management of chronic pain in special populations of PLWH, including persons with substance use and mental health disorders. Finally, a general review of possible pharmacokinetic interactions is included to assist the HIV clinician in the treatment of chronic pain in this population.It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. The Infectious Diseases Society of American considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

Patterns of and reasons for electronic cigarette use in primary care patients.

BACKGROUND: Electronic cigarette (e-cigarette) use is rising in both the general and clinical populations. Little is known about e-cigarette use in primary care, where physicians report discussing e-cigarette use with patients. OBJECTIVE: Identify how and why smokers in primary care use e-cigarettes. DESIGN: Cross-sectional secondary data analysis from a randomized controlled trial of a tablet intervention to deliver the 5As for smoking cessation in primary care. PARTICIPANTS: Current smokers aged 18 and older in three primary care clinics in San Francisco, CA (N = 788). MAIN MEASURES: Patients reported sociodemographics, cigarette smoking habits, quitting readiness, and ever and current use of e-cigarettes. We also asked reasons they have used or would use e-cigarettes. ICD-9 codes from the medical record determined comorbidities. KEY RESULTS: Fifty-two percent (n = 408) of patients reported ever using an e-cigarette, and 20% (n = 154) reported past-30-day use. Ever e-cigarette use was associated with younger age and negatively associated with being seen at practices at a public safety-net hospital compared to a practice at University-affiliated hospital. The most common reason for having used e-cigarettes among ever e-cigarette users, and for interest in future use of e-cigarettes among never e-cigarette users, was to cut down cigarette use. The mean number of days of e-cigarette use in the past 30 increased with duration of e-cigarette use. Most current e-cigarette users did not know the nicotine content of their e-cigarettes. CONCLUSIONS: Over half of smokers in primary care have ever used e-cigarettes, and one-fifth are currently using them. Most reported using e-cigarettes to cut down or quit cigarettes. Primary care providers should be prepared to discuss e-cigarettes with patients. Screening for e-cigarette use may help identify and treat patients interested in changing their cigarette smoking habits.

A Longitudinal Study of Multiple Drug Use and Overdose Among Young People Who Inject Drugs.

OBJECTIVES: To determine the association between multiple drug use and nonfatal overdose among young people (younger than 30 years) who inject drugs. METHODS: We completed a longitudinal study of 173 injection drug users younger than 30 years living in San Francisco, California, between April 2012 and February 2014. RESULTS: The odds of nonfatal overdose increased significantly as heroin and benzodiazepine pill-taking days increased and when alcohol consumption exceeded 10 drinks per day compared with 0 drinks per day. CONCLUSIONS: Heroin, benzodiazepine, and alcohol use were independently associated with nonfatal overdose over time among young people who inject drugs. Efforts to address multiple central nervous system depressant use remain an important component of a comprehensive approach to overdose, particularly among young people.

A delayed injection-site reaction in a patient receiving extended-release naltrexone.

BACKGROUND: Pharmacotherapy, such as oral naltrexone, has proven effective in treating alcohol use disorder, although medication adherence has presented challenges. Although a formulation of extended-release naltrexone for intramuscular injection has been developed to counter daily adherence issues, injection-site reactions can occur within days of depot injection. CASE: The authors report a case of an individual with alcohol use disorder who had a previously undescribed delayed injection-site reaction that occurred 11 days after injection. Subsequent challenge with the medication resulted in recurrence of the reaction. DISCUSSION: Although extended-release naltrexone is generally well tolerated, injection-site reactions can complicate treatment and can appear more than 10 days after medication administration.

Using Interactive Web-Based Screening, Brief Intervention and Referral to Treatment in an Urban, Safety-Net HIV Clinic.

Substance use among people living with HIV is high, and screening, brief intervention, and referral to treatment (SBIRT) is an evidence-based approach to addressing the issue. We examined whether patients would participate in a technology-based SBIRT program in an urban HIV clinic. An SBIRT intervention was programmed into the clinic's web-based patient portal linked to their personal health record. We examined: demographic, health, HIV, and substance use characteristics of participants who completed the web-based intervention compared to those who did not. Fewer than half of the 96 participants assigned to the web-based SBIRT completed it (n = 39; 41 %). Participants who completed the web-based intervention had significantly higher amphetamine SSIS scores than those who did not complete the intervention. Participants whose substance use is more harmful may be more motivated to seek help from a variety of sources. In addition, it is important that technology-based approaches to behavioral interventions in clinics take into consideration feasibility, client knowledge, and comfort using technology.

Addressing Adolescent Substance Use: Teaching Screening, Brief Intervention, and Referral to Treatment (SBIRT) and Motivational Interviewing (MI) to Residents.

BACKGROUND: The American Academy of Pediatrics Committee on Substance Use recommends screening, brief intervention, and referral to treatment (SBIRT) at every adolescent preventive and all appropriate urgent visits. We designed an SBIRT curriculum as part of the adolescent block of a pediatric residency that combined online modules with an in-person workshop, faculty feedback on resident interactions with patients, and resident self-reflection on their motivational interviewing (MI) skills. METHODS: To evaluate the curriculum, we measured resident satisfaction and self-reported confidence in using SBIRT and MI with teens using a retrospective pre/post questionnaire. We used qualitative analysis to evaluate the written comments from faculty observations of patient-trainee interactions and comments from resident self-reflection(s) on patient interactions. RESULTS: Thirty-two residents completed the curriculum. Residents reported high satisfaction with the training. Comparing retrospective pre/post scores on the survey of resident self-reported confidence, measures increased significantly in all domains, including for both alcohol and other drug use. Regarding self-reported MI, skillfulness also increased significantly. Analysis of specific faculty feedback to residents revealed subthemes such as normalizing confidentiality and focusing more on the patient's perspectives on substance use. Resident reflections on their own abilities with SBIRT/MI focused on using the ruler tool and on adapting the MI style of shared decision-making. CONCLUSIONS: A curriculum that combines online training, small-group practice, clinical observations, and self-reflection is valued by residents and can increase resident self-reported confidence in using SBIRT and MI in adolescent encounters. Future studies should examine to what extent confidence predicts performance using standardized measures of MI skillfulness in patient encounters.

Interaction of disulfiram with antiretroviral medications: efavirenz increases while atazanavir decreases disulfiram effect on enzymes of alcohol metabolism.

BACKGROUND AND OBJECTIVES: Alcohol abuse complicates treatment of HIV disease and is linked to poor outcomes. Alcohol pharmacotherapies, including disulfiram (DIS), are infrequently utilized in co-occurring HIV and alcohol use disorders possibly related to concerns about drug interactions between antiretroviral (ARV) medications and DIS. METHOD: This pharmacokinetics study (n=40) examined the effect of DIS on efavirenz (EFV), ritonavir (RTV), or atazanavir (ATV) and the effect of these ARV medications on DIS metabolism and aldehyde dehydrogenase (ALDH) activity which mediates the DIS-alcohol reaction. RESULTS: EFV administration was associated with decreased S-Methyl-N-N-diethylthiocarbamate (DIS carbamate), a metabolite of DIS (p=.001) and a precursor to the metabolite responsible for ALDH inhibition, S-methyl-N,N-diethylthiolcarbamate sulfoxide (DETC-MeSO). EFV was associated with increased DIS inhibition of ALDH activity relative to DIS alone administration possibly as a result of EFV-associated induction of CYP 3A4 which metabolizes the carbamate to DETC-MeSO (which inhibits ALDH). Conversely, ATV co-administration reduced the effect of DIS on ALDH activity possibly as a result of ATV inhibition of CYP 3A4. DIS administration had no significant effect on any ARV studied. DISCUSSION/CONCLUSIONS: ATV may render DIS ineffective in treatment of alcoholism. FUTURE DIRECTIONS: DIS is infrequently utilized in HIV-infected individuals due to concerns about adverse interactions and side effects. Findings from this study indicate that, with ongoing clinical monitoring, DIS should be reconsidered given its potential efficacy for alcohol and potentially, cocaine use disorders, that may occur in this population.

Substance use Attitudes, Beliefs, Experience, and Knowledge Among Nursing and Nursing Assistant Students.

Stigma is a public health concern. Stigmatizing attitudes toward persons with substance use disorders (SUDs) can adversely impact clinical care and outcomes. Beliefs about SUD, prior experience and familiarity to persons with SUD, and educational curricula drive attitudes among health-care workers. In 2019, nursing and nursing assistant students were recruited through an online survey platform. Participants completed an SUD knowledge test and a survey assessing education, beliefs, personal experience, and confidence in recognizing the signs and symptoms of SUD. One hundred and ten health-care students (nursing students, n = 67 and nursing assistant students, n = 43) completed the survey. Among nursing assistant students, endorsing a disease model of addiction (F(2, 40) = 5.83, p < .001, R2 = .23), and personal familiarity with SUD (F(2, 40) = 4.46, p < .001, R2 = .18), were significantly positively predictive of positive regard toward working with persons with SUD. For nursing students, endorsing a disease model of addiction, educational curricula involving persons with SUD, and personal familiarity were significantly positively predictive of positive regard toward working with persons with SUDs (F(2, 61) = 11.52, p < .001, R2 = .36). Interventions to mitigate drug-related stigma among health-care students should center students with personal familiarity, promote the disease concept of addiction, and incorporate contact-based training.

Variability of Hepatitis C Treatment Cascade Outcomes among People Who Inject Drugs across Geographically Diverse Clinics in the US: The HERO Study.

Heterogeneity of outcomes across different clinical trial study sites is often inevitable. Understanding how outcomes differ by site is important for planning future programs and studies. We examined the extent of heterogeneity of hepatitis C virus (HCV) treatment cascade outcomes among persons who inject drugs (PWIDs) across sixteen clinical sites utilized in the HERO Study-a pragmatic randomized trial of HCV treatment support. Treatment cascade outcomes included averages of overall treatment adherence and proportions of treatment initiation, treatment completion, sustained virologic response (SVR) test completion, and SVR achievement. The HERO study utilized 16 clinical sites across the United States (US): eight opioid treatment programs (OTPs) and eight community health centers (CHCs). Variability of the outcomes across the 16 clinical sites was assessed using ranges and intraclass correlation coefficients (ICC) estimated from mixed-effects linear or logistic regression models. Treatment initiation was analyzed in the intention-to-treat (ITT) sample (N = 755); treatment completion, adherence, and SVR test completion in the modified ITT (mITT) sample, which is the sample that initiated treatment (N = 623); and SVR achievement in the mITT and per-protocol (PP, N = 501) samples. Across the 16 clinical sites, the range observed in the averages of overall treatment adherence was from 68% to 81% [ICC = 0.026 (0.005, 0.054)], and the ranges of proportions observed were from 68% to 96% for treatment initiation [ICC (95% CI) = 0.086 (0.051, 0.155)], 60% to 100% for treatment completion [ICC = 0.049 (0.008, 0.215)], 54% to 95% for SVR test completion [ICC = 0.096 (0.006, 0.177)], 46% to 90% for SVR achievement in the mITT sample [ICC = 0.070 (0.014, 0.122)], and 76% to 100% for SVR achievement in the PP sample [ICC = 0.143 (0.021, 0.422)]. The variability of the outcomes across 16 US sites treating HCV among PWIDs appears to be substantial in view of the ranges and ICC values of the outcomes. It is imperative to develop tailored interventions to target the sources of variability and reduce barriers at the patient, provider, clinic, and state policy levels to facilitate more equitable access to HCV treatment and reduce heterogeneity in treatment outcomes.

Current Self-reported Pain Before and After Cure of Hepatitis C Among Persons Who Actively Inject Drugs.

BACKGROUND: Questions remain on the relationship between pain and hepatitis C virus cure among persons who inject drugs (PWID). This study aimed to explore whether achieving hepatitis C virus cure reduced pain severity. METHODS: Prespecified secondary analysis utilized data from a pragmatic clinical trial of care delivery models that enrolled PWIDs between 2016 and 2018 and treated with sofosbuvir/velpatasvir. Current pain severity (0-100) was assessed before and after treatment and 5-point Likert pain scales were used to determine moderate or greater current pain at baseline; the duration and etiology of current pain were not assessed. We used generalized mixed-effects linear models to test whether achieving sustained virologic response (SVR), that is, cure, was associated with lower numeric pain scores (primary outcome) posttreatment, adjusting for potential confounders (age, sex, intervention assignment, time/visit, and baseline pain severity category) and to examine changes in pain over time. Adjusted means estimated from a fitted model for pain severity at each visit were compared between participants who did and did not achieve SVR, both for the sample overall and for the subsample of participants who reported moderate or greater pain at baseline. RESULTS: Of the 501 participants who were randomized, treated with DAAs and had SVR data, moderate or greater pain was reported at baseline in 174 (34.7%) of participants. Numeric pain severity did not significantly differ by SVR status at any study visit except for the week 48 visit from baseline, when the estimated pain score was significantly higher for those who failed treatment (38.0 vs 26.3, P = 0.033). Among the subsample with baseline moderate or greater pain, pain severity scores were significantly lower in subsequent visits compared to the baseline visit, with the exception of week 48 among participants who did not achieve SVR. CONCLUSIONS: Among PWID, achieving SVR did not improve pain severity. However, participants who failed treatment had significantly greater pain at the visit immediately following visit for SVR, which may relate to adverse psychological effects of treatment failure. Among those with baseline moderate or greater pain, pain scores declined post treatment, suggesting that treatment itself (irrespective of SVR) may be associated with improved pain.

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.