Hepatitis C Virus Treatment Initiation Research Articles

High rates of early HCV reinfection after DAA treatment in people with recent drug use attended at mobile harm reduction units

Background and AimsThe World Health Organization recently called for the elimination of hepatitis C virus (HCV) and has identified people who inject drugs (PWID) as a key target population. Clinical trials analyzing currently available all-oral regimens have demonstrated a high degree of efficacy in this population, with a relatively low reinfection rate. There is an urgent need to confirm these data in a harm reduction and active consumption setting. The primary aim of this study was to evaluate the HCV reinfection rate in people with recent drug use followed at low-threshold mobile harm reduction units. MethodWe included people with recent drug use (smoked or injected heroin/cocaine in the previous 6 months) who received HCV treatment and were attended at two low-threshold mobile harm reduction units over 19 months. Sustained virologic response was assessed 12 weeks after therapy (SVR12). The incidence density of HCV reinfection was defined as the number of reinfections per 100-person years (PY) using person-time of observation and was stratified by drug consumption at initiation of HCV treatment. Cox proportional hazard regression analysis was used to assess factors associated with reinfection. ResultsDuring the study period, 160 people who used drugs in the past 6 months completed HCV therapy. 122 (73.9%) and 88 (53.3%) reported injecting drug use in the 6 months and 30 days prior to HCV treatment, respectively. The overall SVR12 was 68% in the ITT analysis (reinfection = failure) and 90.7% in the modified intent-to-treat analysis (considering reinfections as response and removing people who were missing SVR data). The cohort at-risk for reinfection (n = 121) included 47 (39.2%) people who initiated HCV treatment with recently reported abstinence. Reinfection was identified in 10 persons (8.3%), and the median time to reinfection was 7.2 (IQR 4.2–18) months. Total follow-up time at-risk was 101.1-PY (median 0.6 years, IQR 0.3–1.3). The overall incidence of reinfection was 9.8 per 100-PY (95% CI 4.7,18.2). The incidence of reinfection was higher amongst those who had injected drugs in the previous 6 months (16.7 [95%CI 8.0; 30.7] per 100-PY) and in the previous 30 days (18.9 [95% CI 8.1; 37.2] per 100-PY). In the adjusted analysis, only injecting drugs use in the month prior to initiation of HCV therapy was associated with reinfection (aHR 8.7, 95%CI 1.0; 73.6; p 0.04). ConclusionHigh efficacy of HCV treatment, was found in people with recent drug use attended and followed at low-threshold mobile harm reduction units. The high rate of early HCV reinfections in this setting should promote surveillance for reinfection at 7-month intervals after ending the treatment or earlier.

Transitioning from interferon-based to direct antiviral treatment options: A potential shift in barriers and facilitators of treatment initiation among people who use drugs?

BackgroundMultiple barriers for accessing hepatitis C virus (HCV) treatment were identified during the interferon-based (IFN) treatment era for people who inject drugs (PWID). Whether these barriers persist since the introduction of IFN-free direct-acting antiviral (DAA) agents in Canada remains to be documented. This study examined temporal trends in HCV treatment initiation and associated factors during the transition from INF-based to all-oral DAA regimens. MethodsThe study population was drawn from a prospective cohort of PWID in Montreal, Canada. At three-month/one-year intervals between 2011 and 2017, participants with chronic HCV infection completed an interviewer-administered questionnaire on socio-demographic characteristics, drug use and health service utilisation, including HCV treatment. Time-updated Cox multivariate regression models, stratified by DAA + INF (2011-2013) and all-oral DAA (2014–2017) availability periods, were conducted to examine associations between time to HCV treatment initiation and associated barriers and facilitators. ResultsOf 308 participants (85% male, median age 42 [IQR: 33, 50]), 80 (26%) initiated HCV treatment during 915 person-years (PY). Incidence rates increased from 1.6 /100 PY (95%CI:0.9–2.6) in 2011 to 12.7 (10.6–15.1) in 2017 (p-trend = 0.0012). In multivariate analyses, visiting a primary care physician (2011–2013: aHR = 3.63[1.21–10.9]; 2014–2017: 2.52[1.10–5.77]) and frequent injection (0.23[0.05–0.99] and 0.49[0.24–0.99]) were consistently associated with treatment initiation. Participants aged >40 (2.27[1.24–4.13]), receiving opioid agonist therapy (OAT) (2.17[1.19–3.94]), and reporting prior HCV treatment (3.00[1.75–5.15]) were more likely to initiate treatment in the all-oral DAA period. ConclusionTreatment initiation increased between 2011 and 2017, but still remains low among PWID. Primary care visiting was a key facilitator regardless of the period, while engagement in OAT and health services, indicated by prior HCV treatment, increased the likelihood of treatment initiation in the DAA era. These findings suggest that access to health services is essential but not enough to scale up treatment in this population.

A Randomized Controlled Trial of Cash Incentives or Peer Support to Increase HCV Treatment for Persons With HIV Who Use Drugs: The CHAMPS Study.

BackgroundDespite access to direct-acting antivirals, barriers to a hepatitis C virus (HCV) cure persist, especially among persons living with human immunodeficiency virus (HIV) (PLWH) who use drugs. Interventions such as peer mentors or cash incentives may improve the care continuum.MethodsThe CHAMPS (Chronic HepAtitis C Management to ImProve OutcomeS) study randomized 144 PLWH, recruited from an outpatient clinic, with substance use disorders into three treatment groups: usual care (UC) (n = 36), UC plus cash incentives (n = 54), and UC plus peer mentors (n = 54) to evaluate HCV treatment uptake and cure. All participants received 12-weeks of ledipasvir/sofosbuvir (LDV/SOF). Trained peer mentors had well-controlled HIV and HCV. Cash incentives were contingent on visit attendance (maximum $220). The primary endpoint was HCV treatment initiation; secondary endpoints included sustained virologic response (SVR) and HCV reinfection.ResultsThe majority of participants were male (61%), Black (93%), and unemployed (85%). Depression and active drug and alcohol use were common. Overall, 110 of 144 (76%) participants initiated LDV/SOF. Although treatment initiation rates were higher in PLWH randomized to peers (83%, 45 of 54) or cash (76%, 41 of 54) compared to UC (67%, 24 of 36), these differences were not statistically significant (P = .11). Most PLWH who initiated treatment achieved SVR (100 of 110, 91%). LDV/SOF was well tolerated; peers and cash had no effect on drug and alcohol use during therapy. One individual from the cash cohort experienced HCV reinfection.ConclusionAfter removal of system barriers, one-third of PLWH in UC did not initiate HCV treatment. Among those who initiated, SVR rates were high. Research involving PLWH who use drugs should focus on overcoming barriers to treatment initiation.Clinical trial informationThe registration data for the trial are in the ClinicalTrials.gov database, number NCT02402218.

Comparative effectiveness of pharmacist care delivery models for hepatitis C clinics.

The optimal health care delivery models for providing services to patients with infections caused by hepatitis C virus (HCV) remain unknown. Pharmacist involvement may be a key component of optimal HCV care delivery. We examined the comparative effectiveness of a pharmacist-managed HCV clinic versus a pharmacist-assisted HCV clinic. This retrospective cohort study used electronic health record data on patients ≥18 years old initiating HCV treatment at a pharmacist-managed clinic or a pharmacist-assisted clinic within a single health-system between January 2015 and June 2017. Outcomes included treatment completion, sustained virologic response 12 weeks following treatment completion (SVR-12), and dispensation of direct-acting antiviral agents at the institution-based specialty pharmacy. Inverse probability of treatment-weighted (IPTW) logistic regression models were used to compare outcomes between the 2 clinic models. A total of 127 patients initiated HCV treatment therapy: 64 patients from the pharmacist-managed clinic and 63 patients from the pharmacist-assisted clinic. The cohort had a mean age of 55 years, was 51% male, and 68% white. In IPTW analyses, there was no difference in treatment completion (odds ratio [OR], 1.1; 95% confidence interval [CI], 0.1-13.8; p = 0.93), achievement of sustained virologic response at 12 months (SVR-12) (OR, 1.0; 95% CI, 0.2-4.5; p = 0.62), or use of institution-based specialty pharmacy (OR, 0.6; 95% CI, 0.2-1.7; p = 0.33) between pharmacist-managed and pharmacist-assisted clinics. There were no significant differences in outcomes between patients receiving care at the pharmacist-managed HCV clinic and the pharmacist-assisted clinic. Given the frequency of SVR-12 achieved in both groups, both pharmacist-managed and pharmacist-assisted clinic models may be reasonable alternatives for providing outpatient HCV care.

Hepatitis C virus (HCV) related liver fibrosis in people who inject drugs (PWID) at the Stockholm Needle Exchange – evaluated with liver elasticity

Background and aims: Sharing of unsterile injection equipment among people who inject drugs (PWID) is the major transmission-route for hepatitis C (HCV). HCV is highly prevalent in PWID in the Stockholm needle exchange programme (NEP). The frequency of advanced liver fibrosis among the participants is, however, unknown.Methods: From December 2016 to April 2018, all participants with chronic hepatitis C infection (CHC) were offered liver fibrosis evaluation at the Stockholm NEP, including liver stiffness measurement (LSM), a medical history and expanded blood tests to evaluate APRI and FIB-4 scores.Results: A total of 2037 individuals were enrolled of whom 964 (47.3%) had CHC. LSM was performed in 203 (21.1%) of eligible participants of whom 85% had mild fibrosis (LSM ≤9.4 kPa) and 15% advanced fibrosis (LSM ≥9.5 kPa). APRI >1 and FIB-4 > 3.25 only identified 30% of participants with advanced fibrosis. However, all 31(100%) participants with advanced fibrosis were detected when APRI >1 was combined with an age of ≥40 years and an injection drug use (IDU) duration of ≥15 years.Conclusions: We found that the diagnostic work-up for advanced fibrosis can be simplified with this combination of easily available factors. This allows identification of PWID in need of immediate HCV treatment to prevent further disease progression. Furthermore, LSM can be avoided among PWID with mild fibrosis, identified by age <40 years combined with IDU duration of <15 years and APRI score <1. This strategy enhances the HCV care cascade where LSM is not easily available, and will thus facilitate HCV treatment initiation.

2209. Discordance Between FibroSure and FibroScan Results in Hepatitis C and Human Immunodeficiency Virus Co-infected Patients Prior to Treatment for Hepatitis C Virus Infection

BackgroundThe accurate diagnosis of hepatitis C virus (HCV)-related fibrosis is crucial for prognosis and treatment decisions. FibroSure and FibroScan are commonly used to approximate fibrosis prior to HCV treatment. Both methods have been validated for their correlation to the five-level (F0–F4) METAVIR scoring system. However, the correlation between these two tests in HIV/HCV co-infected patients has not been well described. Here, we evaluated the concordance between FibroSure and FibroScan-derived METAVIR results in HIV/HCV co-infected patients.MethodsWe performed a retrospective cross-sectional study of HIV/HCV co-infected patients that were treated between 2014 and 2017 at Drexel University, Philadelphia, PA. We described patient demographics and overall METAVIR scores of treated patients. Further, we compared the concordance between FibroSure and FibroScan results among patients who had both tests before the start of HCV treatment.ResultsOne hundred and thirty-eight HIV/HCV co-infected patients were treated. Most of them (N = 134, 97%) achieved sustained virologic response after 12 weeks of treatment. One hudred and thirty-three patients underwent FibroSure testing before starting HCV treatment. Of those, 62 (47%) fell in the F0–F2 range and 71 (53%) in the F3–F4 range. Of those 133 patients, 21 also underwent FibroScan. Fourteen (67%) fell in the F0–F2 range, while seven (33%) fell in the F3–F4 range. Of the 21 patients who both had FibroSure and FibroScan testing, 12 (57%) had concordant results, while nine (42%) had discrepant results. Of the patients with discrepant results, eight had higher fibrosis scores (F3–F4) with FibroSure, while only one had a higher fibrosis score (F3–F4) with FibroScan.ConclusionIn our study, more than half of HIV/HCV co-infected patients had advanced fibrosis score at the time of HCV treatment. When FibroSure and FibroScan scores were compared, close to half of co-infected patients had discordant results, the preponderance of which had higher FibroSure scores. As early initiation of HCV treatment is crucial to co-infected patients, further studies will need to evaluate the clinical significance of the discrepancy between different non-invasive fibrosis testing systems in co-infected patients.Disclosures All authors: No reported disclosures.

Patient Reaction to Telemedicine for Clinical Management of Hepatitis C Virus Integrated into an Opioid Treatment Program.

Background and Introduction: Virtual integration of hepatitis C virus (HCV) infection management within the opioid treatment program (OTP) through telemedicine may overcome limited treatment uptake encountered when patients are referred offsite. To evaluate the diffusion of telemedicine within the OTP, we conducted a pilot study to assess acceptance of and satisfaction with telemedicine among 45 HCV-infected opioid use disorder (OUD) patients on methadone.Materials and Methods: We administered a modified 11-item telemedicine satisfaction questionnaire after the initial HCV telemedicine evaluation, when initiating HCV treatment, and 3 months post-HCV treatment completion. Among a patient subset, a semistructured interview further assessed issues of participant referral to the telemedicine program as well as convenience and confidentiality with the telemedicine encounters.Results: Patients demonstrated their acceptance of telemedicine-based encounters by referral of additional participants. They highlighted the convenience of on-site treatment with a liver specialist through recognition of the benefit of "one-stop shopping." They also expressed confidence in the privacy and confidentiality of telemedicine encounters.Discussion: In this pilot study, telemedicine appears to be well accepted as a modality for HCV management among OUD patients on methadone. Virtual integration of medical and behavioral therapy through telemedicine warrants further investigation for its use in this population.Conclusions: In this pilot study, we found that a largely racial minority population of substance users grew to accept telemedicine over time with diminished privacy and confidentiality concerns. Telemedicine was well accepted within the OTP community as reflected by participant referral to the program.

Care2Cure: A randomized controlled trial protocol for evaluating nurse case management to improve the hepatitis C care continuum within HIV primary care.

Co-infection with HIV and hepatitis C virus (HCV) results in a threefold increase in relative risk of progression to end stage liver disease and cirrhosis compared to HCV alone. Although curative treatments exist, less than one quarter of people with HCV are linked to care, and even fewer have received treatment. The Care2Cure study is a single-blinded, randomized controlled trial to improve the HCV care continuum among people co-infected with HIV. This ongoing study was designed to test whether a nurse case management intervention can (i) improve linkage to HCV care and (ii) decrease time to HCV treatment initiation among 70 adults co-infected with HIV who are not engaged in HCV care. The intervention is informed by the Andersen Behavioral Model of Health Services Use and consists of nurse-initiated referral, strengths-based education, patient navigation, appointment reminders, and care coordination for drug-drug interactions in the setting of HIV primary care. Validated instruments are used to measure participant characteristics including HCV knowledge, substance use, and depression. The primary outcome is linkage to HCV care (yes/no) within 60 days. In this protocol paper, we describe the first clinical trial to examine the effects of a nurse case management intervention to improve the HCV care continuum among people co-infected with HIV/HCV in the era of all-oral HCV treatment. We describe our work in progress, challenges encountered, and strategies to engage this hard-to-reach population.

Role of a clinical pharmacist as part of a multidisciplinary care team in the treatment of HCV in patients living with HIV/HCV coinfection.

BackgroundThe objective of the study was to evaluate the role of a clinical pharmacist in hepatitis C virus (HCV) treatment of patients living with HIV/HCV coinfection.MethodsWe conducted a descriptive study to quantify the functions of a clinical pharmacist in HCV treatment of patients living with HIV/HCV coinfection who were initiating HCV treatment at a publicly funded clinic between March 18, 2015 and September 15, 2016. The clinical pharmacist’s role was categorized into eight categories: 1) HCV prior authorization (PA) completion; 2) HCV medication adherence counseling; 3) HCV drug-drug interaction (DDI) counseling and screening; 4) HCV medication counseling regarding common adverse events (AEs); 5) HCV counseling regarding HCV treatment outcomes and risk of reinfection; 6) ordering laboratory tests and interpretation of HCV laboratory values; 7) HIV medication AE assessment; and 8) other (including refilling medications and management of other comorbidities).ResultsOne hundred and thirty-five patients initiated treatment during this timeframe: 77.0% were males, 56.3% non-cirrhotic, 77.0% HCV treatment-naïve, 45.9% HCV genotype 1a, and 83.0% initiated on ledipasvir/sofosbuvir. The clinical pharmacist completed 150 PAs, counseled on HCV medication adherence in 79.2% of patients, conducted HCV DDI counseling and screening in 54.2%, and monitored HCV medication AEs in 54.2%. The clinical pharmacist counseled patients on HCV treatment outcomes and risk of reinfection in 53.1%, ordered laboratory tests in 44.8%, and reported and interpreted laboratory values in 44.8%. The clinical pharmacist assessed HIV medication AEs in 54.2% of patients and participated in other activities in 42.7%.ConclusionA clinical pharmacist’s expertise as part of a multidisciplinary care team facilitates optimal treatment outcomes and provides critical support in the management of DAA therapy in individuals living with HIV/HCV coinfection.

Aiming for elimination: Outcomes of a consultation pathway supporting regional general practitioners to prescribe direct-acting antiviral therapy for hepatitis C.

To increase access to treatment, the Australian government enabled general practitioners (GPs) to prescribe direct-acting antivirals (DAAs) to treat hepatitis C virus (HCV)-in consultation with a specialist if inexperienced in HCV management. This study describes the establishment and outcomes of a remote consultation pathway supporting GPs to treat HCV. Key stakeholders from primary and tertiary healthcare services in the Barwon South Western region developed and implemented an HCV remote consultation pathway. Pharmaceutical Benefits Schedule prescription data were used to evaluate GP DAA prescription 12 months pre-and post- pathway implementation. A retrospective review of patients referred for remote consultation for 12 months post- pathway inception was undertaken to determine the care cascade. HCV treatment initiation by GPs increased after implementation of the remote consultation pathway. In the 12-month study period, 74 GPs referred 169 people for remote consultation; 114 (67%) were approved for GP DAA treatment; 48 (28%) were referred for specialist assessment. In total, 119 (71%) patients commenced DAA; 69 were eligible for SVR12 assessment. Post-treatment HCV RNA data were available for 52 (75%) people; 37 achieved SVR12; 15 achieved SVR ranging from week 5 to 11 post-treatment. No treatment failure was detected. Collaborative development and implementation of a remote consultation pathway has engaged regional GPs in managing HCV. Follow-up post-treatment could be improved; however, no treatment failure has been documented. To eliminate HCV as a public health threat, it is vital that specialists support GPs to prescribe DAA.

High Treatment Uptake in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients After Unrestricted Access to Direct-Acting Antivirals in the Netherlands.

The Netherlands has provided unrestricted access to direct-acting antivirals (DAAs) since November 2015. We analyzed the nationwide hepatitis C virus (HCV) treatment uptake among patients coinfected with human immunodeficiency virus (HIV) and HCV. Data were obtained from the ATHENA HIV observational cohort in which >98% of HIV-infected patients ever registered since 1998 are included. Patients were included if they ever had 1 positive HCV RNA result, did not have spontaneous clearance, and were known to still be in care. Treatment uptake and outcome were assessed. When patients were treated more than once, data were included from only the most recent treatment episode. Data were updated until February 2017. In addition, each treatment center was queried in April 2017 for a data update on DAA treatment and achieved sustained virological response. Of 23574 HIV-infected patients ever linked to care, 1471 HCV-coinfected patients (69% men who have sex with men, 15% persons who [formerly] injected drugs, and 15% with another HIV transmission route) fulfilled the inclusion criteria. Of these, 87% (1284 of 1471) had ever initiated HCV treatment between 2000 and 2017, 76% (1124 of 1471) had their HCV infection cured; DAA treatment results were pending in 6% (92 of 1471). Among men who have sex with men, 83% (844 of 1022) had their HCV infection cured, and DAA treatment results were pending in 6% (66 of 1022). Overall, 187 patients had never initiated treatment, DAAs had failed in 14, and a pegylated interferon-alfa-based regimen had failed in 54. Fifteen months after unrestricted DAA availability the majority of HIV/HCV-coinfected patients in the Netherlands have their HCV infection cured (76%) or are awaiting DAA treatment results (6%). This rapid treatment scale-up may contribute to future HCV elimination among these patients.

Management and Treatment of Chronic HBV and HCV Co-Infection and the Impact of Anti-Viral Therapy

Recent reports have demonstrated that chronic hepatitis B virus (HBV) can flare or reactivate when chronic hepatitis C virus (HCV) is treated with direct-acting anti-viral agents (DAAs). Understanding HBV and HCV co-infection is therefore important. Although 40–60% of patients with chronic HCV have been previously exposed to HBV; only about 1–6% has serologic evidence of co-infection. In some patients with co-infection, both HBsurface antigen and HBV DNA may be suppressed to undetectable levels by HCV. Complete serologic screening for HBV should be performed in all patients prior to initiating HCV treatment. Patients with HB surface antigen and isolated anti-HBcore require frequent monitoring during HCV treatment, and some will require treatment. The epidemiology of HBV, HCV, and co-infection; how these viruses interact within the host; the treatments for each virus; the risk of HBV flare during HCV treatment; and how patients with HBV should be managed during HCV treatment will be discussed.

Significant reductions in alcohol use after hepatitis C treatment: results from the ANRS CO13-HEPAVIH cohort.

Few data exist on changes to substance use patterns before and after hepatitis C virus (HCV) treatment. We used longitudinal data of HIV-HCV co-infected individuals to examine whether receiving pegylated interferon (Peg-IFN)-based therapy irrespective of HCV clearance could modify tobacco, cannabis and alcohol use. A prospective cohort of HIV-HCV co-infected individuals was enrolled from 2006. Participants' clinical data were retrieved from medical records and socio-demographic and behavioural characteristics were collected by yearly self-administered questionnaires. Data were collected across 17 hospitals in France. All HIV-HCV co-infected patients who initiated HCV treatment during follow-up and answered items regarding substance use in at least one yearly questionnaire (258 patients, 671 visits). HCV treatment consisted of Peg-IFN-based regimens. Four time-varying outcomes: hazardous alcohol use (Alcohol Use Disorders Identification Test-C>3/4 for women/men), number of alcohol units/month, binge drinking, cannabis and tobacco use. Mixed models assessed the effect of HCV treatment status (not yet treated, treated and HCV-cleared, treated and HCV-chronic) on each outcome. A significant decrease (more than 60% reduction) in both hazardous alcohol use and binge drinking and a reduction of 10 alcohol units/month was observed after HCV treatment (irrespective of HCV clearance). No significant effect of HCV treatment status was found on tobacco use and regular cannabis use, but HCV 'clearers' reported less non-regular use of cannabis. Hepatitis C virus (HCV) treatment appears to help HIV-HCV co-infected patients reduce alcohol use.

Initiating HCV treatment with direct acting agents in opioid agonist treatment: When to start for people co-infected with HIV?

BackgroundDirect acting antivirals (DAA) raise the possibility of eliminating Hepatitis C virus (HCV) among people who inject drugs (PWID). However, concerns regarding treatment retention and reinfection challenge implementation efforts. Opioid agonist treatment (OAT) provides an opportunity to engage HCV-positive PWID into DAA-based treatment. Our objective was to identify when OAT adherence sufficiently improved to inform DAA initiation in OAT settings, assuming continuous OAT retention for at least twelve weeks is necessary to complete the DAA treatment course. MethodsThis was a retrospective cohort study of HCV/HIV co-infected PWID from a population-level linked administrative database of people diagnosed and living with HIV in British Columbia, Canada between 01/1996 and 12/2013. We used monthly follow-up data after initial OAT entry and considered the effects of demographics, disease severity, and HIV and OAT treatment characteristics over time on the probability of subsequent OAT retention of ≥12 weeks, and ≥8 weeks for sensitivity analysis. We fit a generalized linear mixed model to the overall study population, and on stratified samples of those continuously engaged on combination antiretroviral therapy (≥95% ART adherence). A set of monthly indicator variables (months 1, …, 7, >7) were included to fulfil the study objective. ResultsOur study included 1427 HCV/HIV co-infected PWID (39.0% female, 68.8% OAT-naïve). The odds of subsequent twelve-week retention in OAT were statistically significantly greater in month 3 versus month 1 (adjusted odds ratio: 1.18; 95% confidence interval: 1.02, 1.37); and the odds of subsequent 8-week retention in OAT were statistically significantly greater in month 2 versus month 1 (1.15, 95% CI: 1.02, 1.31). Among continuously ART-adherent individuals, the odds of subsequent twelve-week retention were not statistically significantly greater than in month 1 (month 2: 1.12 (0.82, 1.51); month 3: 1.08 (0.79, 1.47); month 4: 1.24 (0.91, 1.71)). ConclusionWe provide evidence that among HCV/HIV co-infected PWID, those retained in OAT for three or more months had higher odds of completing an additional twelve weeks of OAT, compared to no difference in those already receiving ART. These data may have implications for adherence to DAA therapy and further studies are needed to understand the optimal timing of DAA therapy in PWID receiving and not receiving OAT.

Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use.

Multiple direct-acting antiviral (DAA)-based regimens are currently approved that provide one or more interferon-free treatment options for hepatitis C virus (HCV) genotypes (G) 1-6. The choice of a DAA regimen, duration of therapy, and use of ribavirin depends on multiple viral and host factors, including HCV genotype, the detection of resistance-associated amino acid (aa) substitutions (RASs), prior treatment experience, and presence of cirrhosis. In regard to viral factors that may guide the treatment choice, the most important is the infecting genotype because a number of DAAs are genotype-designed. The potency and the genetic barrier may also impact the choice of treatment. One important and debated possible virologic factor that may negatively influence the response to DAAs is the presence of baseline RASs. Baseline resistance testing is currently not routinely considered or recommended for initiating HCV treatment, due to the overall high response rates (sustained virological response >90%) obtained. Exceptions are patients infected by HCV G1a when initiating treatment with simeprevir and elbasvir/grazoprevir or in those with cirrhosis prior to daclatasvir/sofosbuvir treatment because of natural polymorphisms demonstrated in sites of resistance. On the basis of these observations, first-line strategies should be optimized to overcome treatment failure due to HCV resistance.

Highly Successful Hepatitis C Virus (HCV) Treatment Outcomes in Human Immunodeficiency Virus/HCV-Coinfected Patients at a Large, Urban, Ryan White Clinic.

BackgroundThe introduction of direct-acting antivirals (DAAs) created a major paradigm shift in the treatment of chronic hepatitis C. Currently, there is little “real-world” data regarding hepatitis C virus (HCV) treatment outcomes in the human immunodeficiency virus (HIV)/HCV-coinfected population.MethodsThis retrospective cohort study examined HCV treatment outcomes of HIV/HCV-coinfected patients at a large, urban, Ryan White-funded clinic caring for an underserved population. All HIV patients initiating HCV treatment from January 1, 2013 to November 30, 2015 were included in the analysis. The primary end point was sustained virologic response 12 weeks after the end of therapy (SVR12).ResultsA total of 172 patients initiated HCV treatment within the study period: 79% were male, 83% were black, 95% were HCV genotype 1, 79% were HCV treatment naive, and 16% had cirrhosis. At baseline, median CD4 was 494 cells/μL (interquartile range, 316–722) and 92% had HIV ribonucleic acid less than 40 copies/mL. The most common DAA initiated was ledipasvir/sofosbuvir (LDV/SOF) (85%), with 92% receiving 12 weeks of treatment. Overall, SVR12 was 93% by intention-to-treat analysis and 98% by per-protocol analysis. The majority of patients on LDV/SOF did not report any adverse effect. One patient in the ribavirin plus SOF group discontinued treatment due to adverse effect.ConclusionsIn a cohort of mainly black, male, HIV/HCV-coinfected patients at a large, urban, Ryan White clinic, HCV treatment with DAAs resulted in high SVR12 rates and was well tolerated despite real-world challenges including medication access barriers and drug interaction concerns.

Knowledge of hepatitis C and treatment willingness amongst people who inject drugs in an era of direct acting antivirals

BackgroundKnowledge of hepatitis C virus (HCV) is believed to be important in altering risk behaviour, improving engagement in care, and promoting willingness to initiate HCV treatment. We assessed factors associated with HCV knowledge and treatment willingness amongst people who inject drugs (PWID) in an era of direct acting antivirals. MethodsData were derived from three prospective cohort studies of PWID in Vancouver, Canada, between June 2014 and May 2015. HCV knowledge and treatment willingness were assessed using a Likert scale. Multivariable linear regression identified factors associated with higher HCV knowledge and treatment willingness. ResultsAmongst 630 participants, mean scores for HCV knowledge and treatment willingness were 25.41 (standard deviation [SD]: 2.52) out of 30, and 6.83 (SD: 1.83) out of 10, respectively. In multivariable analyses, Caucasian ancestry (adjusted linear regression model estimate [β] 0.50; 95% confidence interval [CI] 0.17, 0.82), employment (β 0.76; 95% CI: 0.38, 1.13), diagnosed mental health disorder (β 0.44; 95% CI: 0.11, 0.78) and previous HCV treatment (β 0.94; 95% CI: 0.46, 1.43) were independently associated with higher knowledge. Downtown Eastside (DTES) residence (i.e., epicenter of Vancouver’s drug scene) was independently associated with lower knowledge (β −0.48; 95% CI: −0.81, −0.15). Greater HCV knowledge (β 0.12; 95% CI: 0.07, 0.17) was independently associated with higher HCV treatment willingness. DTES residence (β −0.31; 95% CI: −0.56, −0.06) and daily crack cocaine smoking (β −0.52; 95% CI: −0.92, −0.13) were independently associated with lower treatment willingness. ConclusionSocioeconomic factors, such as neighborhood residence and employment, were associated with HCV knowledge. Higher HCV knowledge was associated with more HCV treatment willingness. Our findings suggest that increasing HCV knowledge amongst PWID may be an integral component of the HCV cascade of care and that efforts might be best targeted to individuals with greater socioeconomic disadvantage.

Hepatocellular carcinoma decreases the chance of successful hepatitis C virus therapy with direct-acting antivirals

The approval of all-oral direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) has led to the expansion of therapy to include patients with cirrhosis who have hepatocellular carcinoma (HCC). Data on the use of DAAs in HCV+ patients with HCC is limited. The aim of this study was to assess the efficacy of all-oral-DAA regimens in HCV+ cirrhotic patients who have or had HCC compared to those without HCC. A retrospective cohort study was conducted on all cirrhotic patients who were treated for HCV with DAAs at our institution between January 2014 and November 2015. A total of 421 HCV+ patients with cirrhosis were identified, of whom 33% had active or a history of HCC. Failure to achieve sustained virologic response (SVR) occurred in 21% of patients with HCC compared to 12% of patients without HCC (p=0.009). Of the 29 patients with HCC who did not achieve SVR, 27 (93%) occurred when an active tumor was present. DAA therapy in the presence of an inactive tumor or after removal of tumor (resection/transplant) resulted in excellent SVR rates, similar to those without HCC (p<0.0001). In multivariable analysis, the primary predictor of DAA treatment failure was the presence of active HCC at the time of HCV treatment initiation (adjusted odds ratio=8.5, 95% confidence interval=3.90-18.49). The presence of active HCC tumor at the initiation of HCV therapy is significantly associated with all-oral DAA treatment failure. HCV treatment after curative therapies for HCC resulted in excellent SVR. The new medications for hepatitis C have excellent cure rates. However, our study shows that in patients with both liver cancer and hepatitis C, they do not achieve these cure rates. Patients with liver cancer are almost 8 times more likely to fail hepatitis C treatment than patients without liver cancer.

Barriers to Hepatitis C Virus (HCV) Treatment Initiation in Patients With Human Immunodeficiency Virus/HCV Coinfection: Lessons From the Interferon Era.

Hepatitis C is a major cause of mortality among human immunodeficiency virus (HIV)-infected patients, yet hepatitis C virus (HCV) treatment uptake has historically been low. Although the removal of interferon removes a major barrier to HCV treatment uptake, oral therapies alone may not fully eliminate barriers in this population. Within the Johns Hopkins Hospital HIV cohort, a nested case-control study was conducted to identify cases, defined as patients initiating HCV treatment between January 1996 and 2013, and controls, which were selected using incidence density sampling (3:1 ratio). Controls were matched to cases on date of enrollment. Conditional logistic regression was used to evaluate factors associated with HCV treatment initiation. Among 208 treated cases and 624 untreated controls, the presence of advanced fibrosis (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.26-3.95), recent active drug use (OR, 0.36; 95% CI, 0.19-0.69), and non-black race (OR, 2.01; 95% CI, 1.26-3.20) were independently associated with initiation of HCV therapy. An increasing proportion of missed visits was also independently associated with lower odds of HCV treatment (25%-49% missed visits [OR, 0.49; 95% CI, 0.27-0.91] and ≥50% missed visits [OR, 0.24; 95% CI, 0.12-0.48]). Interferon-free treatments may not be sufficient to fully overcome barriers to HCV care in HIV-infected patients. Interventions to increase engagement in care for HIV and substance use are needed to expand HCV treatment uptake.

Chronic hepatitis C burden and care cascade in Australia in the era of interferon-based treatment.

Interferon-free direct-acting antiviral regimens for hepatitis C virus (HCV) infection have been recently available in Australia, beginning a new era in clinical and public health management of HCV infection. This study provided updated estimates of the HCV infection care cascade and burden in Australia as a reliable platform for assessing the future impact of interferon-free therapies. A modeling approach was applied to estimate the number of individuals living with chronic HCV infection and with various liver disease stages. Data from national registries of HCV notification and liver transplantation, literature review, and expert consensus informed the model parameters. HCV notification and Pharmaceutical Benefits Scheme data were used to estimate the number of HCV diagnosed individuals and treatment uptake. In 2014, an estimated 230 470 individuals (range: 180 490-243 990) were living with HCV, among whom 75% were diagnosed (n = 172 720; range: 156 720-188 770), 20% had ever received treatment (n = 45 000; range: 39 280-50 720), and 11% had been cured (n = 24 750; range: 21 520-27 990). Among individuals with HCV infection, the proportion with hepatic fibrosis stage ≥F3 doubled during the last decade, increasing from 9% (n = 18 580) in 2004 to 19% (n = 44,730) in 2014. Individuals initiating HCV treatment increased from 1100 in 1997 to 3840 in 2007, plateaued until 2010 and decreased to 2790 in 2014. The burden of HCV-related liver disease has increased markedly. Although the proportion diagnosed was high, treatment uptake remained low, with no increase over the last 7 years. Reducing the HCV burden in Australia requires scale-up of interferon-free HCV therapies.