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.

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.

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.

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.

Changes in Health-related Quality of Life for Hepatitis C Virus-Infected People Who Inject Drugs While on Opioid Agonist Treatment Following Sustained Virologic Response.

BACKGROUND: Although efforts to treat hepatitis C virus (HCV) in people who inject drugs (PWID) yield high rates of sustained virologic response (SVR), the relationship between successful HCV treatment and health-related quality of life (HRQOL) among PWID is poorly understood. We examined HRQOL changes throughout HCV treatment and post-treatment for PWID achieving SVR. METHODS: Participants included 141 PWID who achieved SVR following HCV treatment onsite at 3 opioid agonist treatment (OAT) clinics in the Bronx, New York. EQ-5D-3L assesses 5 health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), producing an index of HRQOL ranging from 0 to 1. EQ-5D-3L was measured at baseline; 4, 8, and 12 weeks during treatment; and 12 and 24 weeks post-treatment. Linear mixed effects regression models assessed changes in the mean EQ-5D-3L index over time. RESULTS: Mean EQ-5D-3L index baseline was 0.66 (standard error [SE] = 0.02). While over half the population reported no baseline problems with self-care (85.1%), usual activities (56.0%), and mobility (52.5%), at least two-thirds reported problems with pain/discomfort (78.0%) and anxiety/depression (66.0%). Twenty-four weeks post-treatment, proportions reporting pain/discomfort and anxiety/depression decreased by 25.7% and 24.0%, respectively. Mean EQ-5D-3L index significantly improved during treatment (P < .0001), and improvement was sustained following treatment completion, with mean EQ-5D-3L index of 0.77 (SE = 0.02) 12 weeks post-SVR. CONCLUSIONS: HCV treatment led to sustained improvement in HRQOL for PWID on OAT who achieved SVR. Future research is necessary to determine whether improvements in HRQOL can be sustained beyond 12 weeks post-SVR.

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.

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.

Hepatitis C Virus Direct-Acting Antiviral Treatment Adherence Patterns and Sustained Viral Response Among People Who Inject Drugs Treated in Opioid Agonist Therapy Programs.

BACKGROUND: Adequate medication adherence is critical for achieving sustained viral response (SVR) of hepatitis C virus (HCV) among people who inject drugs (PWID). However, it is less known which patterns of direct-acting antiviral (DAA) treatment adherence are associated with SVR in this population or what factors are associated with each pattern. METHODS: The randomized 3-arm PREVAIL study used electronic blister packs to obtain daily time frame adherence data in opiate agonist therapy program settings. Exact logistic regressions were applied to test the associations between SVR and 6 types of treatment adherence patterns. RESULTS: Of the 113 participants treated with combination DAAs, 109 (96.5%) achieved SVR. SVR was significantly associated with all pattern parameters except for number of switches between adherent and missed days: total adherent daily doses (exact adjusted odds ratio [AOR] = 1.12; 95% confidence interval [CI] = 1.04-1.22), percent total doses (1.09; 1.03-1.16), days on treatment (1.16; 1.05-1.32), maximum consecutive adherent days (1.34; 1.06-2.04), and maximum consecutive nonadherent days (0.85; .74-.95 = 0.003). SVR was significantly associated with total adherent doses in the first 2 months of treatment, it was not in the last month. While alcohol intoxication was significantly associated with frequent switches, drug use was not associated with any adherence pattern. CONCLUSIONS: Consistent maintenance of adequate total dose adherence over the entire course of HCV treatment is important in achieving SVR among PWID. Additional integrative addiction and medical care may be warranted for treating PWID who experience alcohol intoxication.

Considerations for the Design of Pre-exposure Prophylaxis (PrEP) Interventions for Women: Lessons Learned from the Implementation of a Novel PrEP Intervention.

Pre-exposure prophylaxis (PrEP) uptake among women in the United States has been low. To increase uptake, we developed a peer outreach and navigation PrEP intervention. Semi-structured qualitative interviews with 32 cisgender women and 3 transgender women were conducted to assess the intervention. We used a thematic approach to identify barriers to, and facilitators of the intervention. Facilitators included interest in PrEP, offer of health and social services, the intervention's women-focused approach, and peer outreach and navigation. Barriers were perceived HIV risk, concerns about medication side effects or interactions, housing insecurity and travel, co-occurring health-related conditions, and caregiving responsibilities. We recommend that future interventions consider packaging PrEP in local community settings, such as syringe exchange programs; include services such as food and housing assistance; use peers to recruit and educate women; integrate a culturally appropriate women's focus; and consider providing same-day PrEP.

A Pilot Study to Evaluate a Novel Pre-exposure Prophylaxis Peer Outreach and Navigation Intervention for Women at High Risk for HIV Infection.

Pre-exposure prophylaxis (PrEP) uptake remains woefully low among U.S. women at high risk for HIV acquisition. We evaluated a pilot intervention which involved Peers providing brief PrEP education and counseling at mobile syringe exchange sites and at sex worker and syringe exchange drop-in centers followed by navigation to PrEP care. Peers recruited English-proficient, self-identified women (i.e., cisgender and transgender women and persons with other transfeminine identities) over a 3-month period and delivered the intervention to 52 HIV-negative/status unknown participants. Thirty-eight participants (73.1%) reported PrEP interest, 27 (51.9%) accepted the offer of a PrEP appointment, 13 (25.0%) scheduled a PrEP appointment, 3 (5.8%) attended an initial PrEP appointment, and none were prescribed PrEP. We found a gap between PrEP interest and connecting women to PrEP care. Further study is needed to understand this gap, including exploring innovative approaches to delivering PrEP care to women at highest risk for HIV.

Low Hepatitis C Reinfection Following Direct-acting Antiviral Therapy Among People Who Inject Drugs on Opioid Agonist Therapy.

BACKGROUND: Direct-acting antiviral (DAA) therapy is highly effective in people who inject drugs (PWID); however, rates, specific injection behaviors, and social determinants associated with hepatitis C virus (HCV) reinfection following DAA therapy among PWID on opioid agonist therapy (OAT) are poorly understood. METHODS: PREVAIL was a randomized controlled trial that assessed models of HCV care for 150 PWID on OAT. Those who achieved sustained virologic response (SVR) (n = 141; 94%) were eligible for this extension study. Interviews and assessments of recurrent HCV viremia occurred at 6-month intervals for up to 24 months following PREVAIL. We used survival analysis to analyze variables associated with time to reinfection. RESULTS: Of 141 who achieved SVR, 114 had a least 1 visit in the extension study (62% male; mean age, 52 years). Injection drug use (IDU) was reported by 19% (n = 22) in the extension study. HCV reinfection was observed in 3 participants. Over 246 person-years of follow-up, the incidence of reinfection was 1.22/100 person-years (95% CI, 0.25-3.57). All reinfections occurred among participants reporting ongoing IDU. The incidence of reinfection in participants reporting ongoing IDU (41 person-years of follow-up) was 7.4/100 person-years (95% CI, 1.5-21.6). Reinfection was associated with reporting ongoing IDU in the follow-up period (P < .001), a lack confidence in the ability to avoid contracting HCV (P < .001), homelessness (P = .002), and living with a PWID (P = .007). CONCLUSIONS: HCV reinfection was low overall, but more common among people with ongoing IDU following DAA therapy on OAT, as well as those who were not confident in the ability to avoid contracting HCV, homeless, or living with a PWID. Interventions to mediate these risk factors following HCV therapy are warranted.

Cost-effectiveness of Hepatitis C Virus Treatment Models for People Who Inject Drugs in Opioid Agonist Treatment Programs.

BACKGROUND: Many people who inject drugs in the United States have chronic hepatitis C virus (HCV). On-site treatment in opiate agonist treatment (OAT) programs addresses HCV treatment barriers, but few evidence-based models exist. METHODS: We evaluated the cost-effectiveness of HCV treatment models for OAT patients using data from a randomized trial conducted in Bronx, New York. We used a decision analytic model to compare self-administered individual treatment (SIT), group treatment (GT), directly observed therapy (DOT), and no intervention for a simulated cohort with the same demographic characteristics of trial participants. We projected long-term outcomes using an established model of HCV disease progression and treatment (hepatitis C cost-effectiveness model: HEP-CE). Incremental cost-effectiveness ratios (ICERs) are reported in 2016 US$/quality-adjusted life years (QALY), discounted 3% annually, from the healthcare sector and societal perspectives. RESULTS: For those assigned to SIT, we projected 89% would ever achieve a sustained viral response (SVR), with 7.21 QALYs and a $245 500 lifetime cost, compared to 22% achieving SVR, with 5.49 QALYs and a $161 300 lifetime cost, with no intervention. GT was more efficient than SIT, resulting in 0.33 additional QALYs and a $14 100 lower lifetime cost per person, with an ICER of $34 300/QALY, compared to no intervention. DOT was slightly more effective and costly than GT, with an ICER > $100 000/QALY, compared to GT. In probabilistic sensitivity analyses, GT and DOT were preferred in 91% of simulations at a threshold of <$100 000/QALY; conclusions were similar from the societal perspective. CONCLUSIONS: All models were associated with high rates of achieving SVR, compared to standard care. GT and DOT treatment models should be considered as cost-effective alternatives to SIT.

Factors and HCV treatment outcomes associated with smoking among people who inject drugs on opioid agonist treatment: secondary analysis of the PREVAIL randomized clinical trial.

BACKGROUND: Cigarette smoking has emerged as a leading cause of mortality among people with hepatitis C virus (HCV). People who inject drugs (PWID) represent the largest group of adults infected with HCV in the US. However, cigarette smoking remains virtually unexplored among this population. This study aimed at (1) determining prevalence and correlates of cigarette smoking among HCV-infected PWID enrolled in opiate agonist treatment programs; (2) exploring the association of smoking with HCV treatment outcomes including adherence, treatment completion and sustained virologic response (SVR); and 3) exploring whether cigarette smoking decreased after HCV treatment. METHODS: Participants were 150 HCV-infected PWID enrolled in a randomized clinical trial primarily designed to test three intensive models of HCV care. Assessments included sociodemographics, presence of chronic health and psychiatric comorbidities, prior and current drug use, quality of life, and HCV treatment outcomes. RESULTS: The majority of the patients (84%) were current cigarette smokers at baseline. There was a high prevalence of psychiatric and medical comorbidities in the overall sample of PWID. Alcohol and cocaine use were identified as correlates of cigarette smoking. Smoking status did not influence HCV treatment outcomes including adherence, treatment completion and SVR. HCV treatment was not associated with decreased cigarette smoking. CONCLUSIONS: The present study showed high prevalence of cigarette smoking among this population as well as identified correlates of smoking, namely alcohol and cocaine use. Cigarette smoking was not associated with HCV treatment outcomes. Given the detrimental effects that cigarette smoking and other co-occurring, substance use behaviors have on HCV-infected individuals' health, it is imperative that clinicians treating HCV also target smoking, especially among PWID. The high prevalence of cigarette smoking among PWID will contribute to growing morbidity and mortality among this population even if cured of HCV. Tailored smoking cessation interventions for PWID along with HCV treatment may need to be put into clinical practice. TRIAL REGISTRATION: NCT01857245 . Registered May 20, 2013.

Intensive Models of Hepatitis C Care for People Who Inject Drugs Receiving Opioid Agonist Therapy: A Randomized Controlled Trial.

Background: Many people who inject drugs (PWID) are denied treatment for hepatitis C virus (HCV) infection, even if they are receiving opioid agonist therapy (OAT). Research suggests that HCV in PWID may be treated effectively, but optimal models of care for promoting adherence and sustained virologic response (SVR) have not been evaluated in the direct-acting antiviral (DAA) era. Objective: To determine whether directly observed therapy (DOT) and group treatment (GT) are more effective than self-administered individual treatment (SIT) in promoting adherence and achieving SVR among PWID receiving OAT. Design: Three-group, randomized controlled trial conducted from October 2013 to April 2017. (ClinicalTrials.gov: NCT01857245). Setting: Three OAT programs in Bronx, New York. Participants: Persons aged 18 years and older with genotype 1 HCV infection who were willing to receive HCV therapy on site in the OAT program. Of 190 persons screened, 158 were randomly assigned to a study group and 150 initiated treatment: DOT (n = 51), GT (n = 48), and SIT (n = 51). Intervention: 2 intensive interventions (DOT and GT) and 1 control condition (SIT). Measurements: Primary: adherence, measured by using electronic blister packs. Secondary: HCV treatment completion and SVR 12 weeks after treatment completion. Results: Mean age was 51 years; 65% of participants had positive results on urine drug testing during the 6 months before treatment, and 75% reported ever injecting drugs. Overall adherence, estimated from mixed-effects models using the daily timeframe, was 78% (95% CI, 75% to 81%) and was greater among participants randomly assigned to DOT (86% [CI, 80% to 92%]) than those assigned to SIT (75% [CI, 70% to 81%]; difference, 11% [CI, 5% to 18%]; Bonferroni-corrected P = 0.001). No significant difference in adherence was observed between participants randomly assigned to GT (80% [CI, 74% to 86%]) and those assigned to SIT (difference, 4.7% [CI, -2% to 11%]; Bonferroni-corrected P = 0.29). The HCV treatment completion rate was 97%, with no differences among groups (P = 0.53). Overall SVR was 94% (CI, 89% to 97%); the SVR rate was 98% in the DOT group, 94% in the GT group, and 90% in the SIT group (P = 0.152). Limitation: These findings may not be generalizable to PWID not enrolled in OAT programs. Conclusion: All models of onsite HCV care delivered to PWID in OAT programs resulted in high SVR, despite ongoing drug use. Directly observed therapy was associated with greater adherence than SIT. Primary Funding Source: National Institute on Drug Abuse and Gilead Sciences.

Hepatitis C elimination among people who inject drugs: Challenges and recommendations for action within a health systems framework.

The burden of hepatitis C infection is considerable among people who inject drugs (PWID), with an estimated prevalence of 39%, representing an estimated 6.1 million people who have recently injected drugs living with hepatitis C infection. As such, PWID are a priority population for enhancing prevention, testing, linkage to care, treatment and follow-up care in order to meet World Health Organization (WHO) hepatitis C elimination goals by 2030. There are many barriers to enhancing hepatitis C prevention and care among PWID including poor global coverage of harm reduction services, restrictive drug policies and criminalization of drug use, poor access to health services, low hepatitis C testing, linkage to care and treatment, restrictions for accessing DAA therapy, and the lack of national strategies and government investment to support WHO elimination goals. On 5 September 2017, the International Network of Hepatitis in Substance Users (INHSU) held a roundtable panel of international experts to discuss remaining challenges and future priorities for action from a health systems perspective. The WHO health systems framework comprises six core components: service delivery, health workforce, health information systems, medical procurement, health systems financing, and leadership and governance. Communication has been proposed as a seventh key element which promotes the central role of affected community engagement. This review paper presents recommended strategies for eliminating hepatitis C as a major public health threat among PWID and outlines future priorities for action within a health systems framework.

Rationale, design, and methodology of a trial evaluating three models of care for HCV treatment among injection drug users on opioid agonist therapy.

BACKGROUND: People who inject drugs (PWID) constitute 60% of the approximately 5 million people in the U.S. infected with hepatitis C virus (HCV). Treatment of PWID is complex due to addiction, mental illness, poverty, homelessness, lack of positive social support, poor adherence-related skills, low motivation and knowledge, and poor access to and trust in the health care system. New direct-acting antiviral medications are available for HCV with high cure rates and few side effects. The life expectancy and economic benefits of new HCV treatments will not be realized unless we determine optimal models of care for the majority of HCV-infected patients. The purpose of this study is to evaluate the effectiveness of directly observed therapy and group treatment compared with self-administered individual treatment in a large, urban opioid agonist therapy clinic setting in the Bronx, New York. METHODS/DESIGN: In this randomized controlled trial 150 PWID with chronic HCV were recruited from opioid agonist treatment (OAT) clinics and randomized to one of three models of onsite HCV treatment in OAT: 1) modified directly observed therapy; 2) group treatment; or 3) control - self-administered individual treatment. Participants were age 18 or older, HCV genotype 1, English or Spanish speaking, treatment naïve (or treatment experienced after 12/3/14), willing to receive HCV treatment onsite, receiving methadone or buprenorphine at the medication window at least once per week, and able to provide informed consent. Outcomes of interest include adherence (as measured by self-report and electronic blister packs), HCV treatment completion, sustained virologic response, drug resistance, and cost-effectiveness. DISCUSSION: This paper describes the design and rationale of a randomized controlled trial comparing three models of care for HCV therapy delivered in an opioid agonist treatment program. Our trial will be critical to rigorously identify models of care that result in high adherence and cure rates. Use of blister pack technology will help us determine the role of adherence in successful cure of HCV. Moreover, the trial methodology outlined here can serve as a template for the development of future programs and studies among HCV-infected drug users receiving opioid agonist therapy, as well as the cost-effectiveness of such programs. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov ( NCT01857245 ). Trial registration was obtained prospectively on May 20th, 2013.

Cigarette Smoking Behaviors and Beliefs in Persons Living With Hepatitis C.

BACKGROUND AND RATIONALE: Tobacco use is common among persons living with hepatitis C (PLHC), yet little is known about their smoking behaviors and beliefs. Modern hepatitis C treatment offers a unique opportunity to intensively engage this population about other health risks, including smoking. MAIN RESULTS: Seventy-seven tobacco users (40 hepatitis C virus [HCV] seropositive and 37 HCV seronegative) enrolled in an interview study in a New York City clinic. The mean age was 51.6, 57.1% were male, 40.3% Latino, and 49.4% black. 67.5% were single and 18.2% were employed. HCV+ smokers differed from HCV- smokers in having a higher prevalence of illicit substance use, depression, and hypertension. PLHC smokers were highly motivated to quit, with 52.5% stating an intention to quit within 30 days. Most of the PLHC smokers had used cessation-directed pharmacotherapy, but almost none had tried a quitline or a quit smoking website. PLHC smokers scored higher on the intrapersonal locus of control subscale. Almost a quarter (22.5%) believed that smoking "helped fight the HCV." CONCLUSIONS: PLHC smokers have a high burden of psychiatric and substance use comorbidity. They exhibit characteristics that distinguish them from uninfected smokers, and many harbor false beliefs about imagined benefits of smoking. They are highly motivated to quit but underutilize cessation aids. Without aggressive intervention, smoking-related morbidity will likely mute the health benefits and longevity gains associated with hepatitis C treatment. Research such as this may prove useful in guiding the development of future tobacco treatment strategies. IMPLICATIONS: This is the first paper to examine, in detail, sociobehavioral correlates of tobacco use in PLHC. PLHC are recognized by the Department of Health and Human Services as a high-priority health disparities population. We are not aware of any tobacco treatment services designed specifically for PLHC. The first step in designing an intervention is defining the characteristics of the target group. Our findings will begin to address this need, and may prove useful in optimizing tobacco treatment strategies for smokers living with hepatitis C.

No Differences in Achieving Hepatitis C Virus Care Milestones Between Patients Identified by Birth Cohort or Risk-Based Screening.

BACKGROUND & AIMS: National hepatitis C virus (HCV) screening guidelines recommended 1-time testing of persons born between 1945 and 1965. METHODS: We performed a retrospective study to compare care milestones achieved by HCV-infected patients identified by birth cohort versus risk-based screens. RESULTS: We determined the proportions of patients newly identified with HCV infection who met care milestones (viral load, referral to and evaluation by a specialist, offer of treatment, initiation of treatment, and sustained viral response) and the time it took to reach them. We found no differences in HCV care milestones for patients identified via birth cohort testing versus risk-based screening. Overall, only 43% of HCV antibody-positive patients were referred to care, and less than 4% started treatment. The time to each care milestone was lengthy and varied greatly; treatment was initiated in a median of 308 days. CONCLUSIONS: Although birth cohort testing will likely increase identification of patients with HCV infection, it does not seem to increase the number of patients that meet management milestones. New methods are needed to increase access to care and establish efficient models of health care delivery.

A Birth-cohort testing intervention identified hepatitis c virus infection among patients with few identified risks: a cross-sectional study.

BACKGROUND: International guidelines and U.S. guidelines prior to 2012 only recommended testing for hepatitis C virus (HCV) infection among patients at risk, but adherence to guidelines is poor, and the majority of those infected remain undiagnosed. A strategy to perform one-time testing of all patients born during 1945-1965, birth cohort testing, may diagnose HCV infection among patients whose risk remains unknown. We sought to determine if a birth-cohort testing intervention for HCV antibody positivity helped identify patients with fewer documented risk factors or medical indications than a pre-intervention, risk-based testing strategy. METHODS: We used a cross-sectional design with retrospective electronic medical record review to examine patients identified with HCV antibody positivity (Ab+) during a pre-intervention (risk-based) phase, the standard of care at the time, vs. a birth-cohort testing intervention phase. We compared demographic and clinical characteristics and HCV risk-associated factors among patients whose HCV Ab + was identified during the pre-intervention (risk-based testing) vs. post birth-cohort intervention phases. Study subjects were patients identified as HCV-Ab + in the baseline (risk-based) and birth-cohort testing phases of the Hepatitis C Assessment and Testing (HepCAT) Project. RESULTS: Compared to the risk-based phase, patients newly diagnosed with HCV Ab + after the birth-cohort intervention were significantly less likely to have a history of any substance abuse (30.5% vs. 49.5%, p = 0.02), elevated alanine transaminase levels of > 40 U/L (22.0% vs. 46.7%, p = 0.002), or the composite any risk-associated factor (55.9% vs. 79.0%, p = 0.002). CONCLUSIONS: Birth-cohort testing is an useful strategy for identifying previously undiagnosed HCV Ab + because it does not require providers ask risk-based questions, or patients to disclose risk behaviors, and appears to identify HCV Ab + in patients who would not have been identified using a risk-based testing strategy.