Published Work.

Barriers to Hepatitis B Treatment: A Multicentre Cross-Sectional Registry and Survey Study by the Canadian Hepatitis B Network.

Ko HH, Vienneau J, Cooper CL, Crotty P, Congly SE, Brahmania M, Ramji A, Kelly E, Crawley AM, Doucette K, Meier-Stephenson V, Ma M, Fung SK, Wong DK, Feld J, Faisal N, Kaita K, Osiowy C, Elkhashab M, Tam E, Wong A, Bailey R, Wong P, Sebastiani G, Chen T, Conway B, Truong D, Tsoi K, Nudo C, Zhu J, Poulin S, Shaheen AA, Coffin CS

Liver international : official journal of the International Association for the Study of the Liver

BACKGROUND & AIMS: Chronic hepatitis B (CHB) remains a leading cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide, yet treatment uptake is suboptimal even in high-resource settings. This pan-Canadian study aimed to quantify treatment gaps within the Canadian Hepatitis B Network (CanHepB) Registry, compare characteristics of treatment-eligible but untreated patients to those receiving therapy, and assess patient and specialist perspectives on barriers to treatment. METHODS: A cross-sectional, retrospective analysis of 1983 adults with CHB followed in 18 Canadian hepatitis B specialty clinics between January 2018 and November 2024. Treatment eligibility was determined using the 2018 Canadian Association for the Study of the Liver guidelines. An anonymous survey captured patient-reported barriers and perspectives (n = 191), while a separate survey evaluated specialist perceptions (n = 54). RESULTS: Among 881 untreated patients, 46.4% (n = 409) were treatment eligible. Compared with the treatment group (n = 1087), the treatment-eligible but untreated patients were younger (median 47.3 vs. 54.5 years), more frequently female (54.2% vs. 39.7%), and more likely to be of Black/African/Caribbean origin (18.2% vs. 9.7%). They had a lower prevalence of cirrhosis (2.4% vs. 20.3%), HCC (0.7% vs. 9.3%), and hypertension (17.1% vs. 22.9%), but a higher prevalence of steatotic liver disease (36.4% vs. 24.6%) and dyslipidemia (14.7% vs. 10.8%). Among untreated respondents, concerns included side effects, the need for long-term therapy, and lack of curative options. Conversely, specialists identified cost as the primary barrier and side effects as the least concerning. CONCLUSION: This nationwide study reveals a significant treatment gap in CHB care, driven by demographic disparities and a mismatch between patient concerns and clinician perceptions.

Worldwide Impact of ACIP’s 2025 Overhaul.

Bont L, Conway B, Mazur N

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

Efficacy and Safety of Glecaprevir/Pibrentasvir in Participants with Chronic HCV Infection and Comorbidities or Multiple Concomitant Medications: An Integrated Analysis.

Cooper C, Raina SA, Johnson L, Feld JJ, Brown A, Martinez A, Conway B, Gordon SC, Asselah T, Uribe L, Li M, Iacob A, Marcinak J, Semizarov D, Pol S

Infectious diseases and therapy

INTRODUCTION: Glecaprevir/pibrentasvir (G/P) is globally approved for the treatment of chronic hepatitis C virus (HCV) infection and for acute HCV infection in the USA. The efficacy and safety of G/P has been clinically demonstrated in participants with chronic HCV. We used clinical trial data to assess the efficacy, safety, and tolerability of G/P in participants with comorbidities or on multiple concomitant medications with potential for drug-drug interaction with G/P. METHODS: An integrated pooled analysis across 21 randomized, controlled phase 2 and 3 trials of participants who received G/P for 8, 12, or 16 weeks was performed. Participants were stratified by comorbidity or population of interest and by number of concomitant medications received. RESULTS: This analysis included 6547 participants with chronic HCV infection. Overall, 2068 (31.6%) had cardiovascular disorders, 2031 (31.0%) reported illicit drug use, 1373/4617 (29.7%) reported injection drug use, 1810 (27.6%) had psychiatric disorders, 1169 (17.9%) had compensated cirrhosis, and 291 (4.4%) had human immunodeficiency virus (HIV)-HCV coinfection. Additionally, 4524 (69.1%) were receiving ≥ 1 concomitant medication. According to the Liverpool HEP Drug Interactions checker, 1357 (20.7%) were receiving a concomitant medication with mechanistic potential or weak potential drug-drug interaction with G/P. Overall, 94.3% (6174/6547) achieved sustained virologic response at 12 weeks post-treatment (SVR12: 98.7% [6174/6257] when excluding non-virologic treatment failure), with consistent rates between subgroups. In total, 3140 (48.0%) of participants experienced an adverse event (AE) and 1638 (25.0%) experienced a treatment-related AE. Serious AEs and treatment-related serious AEs were observed in 165 (2.5%) and 6 (0.1%) participants, respectively. In subgroup analyses, the highest rate of treatment-related serious AEs was observed in participants with HIV-HCV coinfection (0.7%). Mean compliance was 99.6%, which was consistent across subgroups and by number of concomitant medications received. CONCLUSIONS: These pooled data support the efficacy, safety, and tolerability of G/P in participants with chronic HCV infection and comorbidities or who are on multiple concomitant medications.

Addressing digital exclusion to improve access to HIV and viral hepatitis care for people who experience criminalization: a mixed methods evaluation of a quality improvement project.

Tiwana A, Gale N, Mahay M, Barker T, Hasdell R, Young P, Korchinski M, Schmitz D, Luster D, Ramji A, MacIsaac J, Conway B, Fraser C, Bartlett S

International journal for equity in health

BACKGROUND: People who experience criminalization, such as those who use drugs, are incarcerated, and are affected by homelessness, have a high prevalence of HIV and/or hepatitis C virus (HCV) infection and low treatment uptake in British Columbia. Barriers to care include unreliable means of maintaining contact with healthcare providers. To reduce these barriers, the Test, Link, Call (TLC) Project provides cell phones and peer health mentors to support access to HIV and/or HCV care. This study aims to determine the outcomes and acceptability of TLC and its impact on care engagement. METHODS: A mixed-methods evaluation was conducted over the first 29 months (October 2021–March 2024) of the TLC Project. Data were collected concurrently in two rounds: the first after one year and the second two years after launch. Qualitative data were collected using semi-structured interviews conducted with healthcare providers (n = 8), peer health mentors (n = 6), and program participants (n = 20). Quantitative data, including demographic and clinical information, were gathered through program records and cross-sectional clinical chart reviews. Factors associated with HCV treatment uptake were assessed among HCV RNA positive participants (n = 245) using multivariate logistic regression. Data from both rounds were integrated for comprehensive analysis. RESULTS: 273 participants were enrolled in HCV care, and 26 in HIV care. Interviewees found TLC highly acceptable and effective. Positive outcomes included increased access to health and social services, connection to loved ones, independence, and safety. Challenges included phone theft and digital literacy issues. Overall, 57% of TLC participants enrolled for HCV care initiated curative treatment, compared to 40% among people who currently inject drugs in the provincial administrative database in 2020. The multivariate logistic regression analysis suggested that gender, housing stability, safer supply prescriptions, and length of involvement in the TLC program are predictive factors influencing treatment initiation. CONCLUSIONS: The provision of cell phones and peer health mentors effectively increased engagement in HIV and HCV care, demonstrating substantial benefits despite some challenges. This cost-effective intervention could be expanded to support people who experience criminalization in other geographic locations and addressing other health conditions, such as syphilis and substance use disorder.

Achieving the UNAIDS 95-95-95 targets: a right, not a privilege.

Wiesmann C, Conway B

AIDS (London, England)

Reinfection following successful direct-acting antiviral therapy for hepatitis C virus infection among people with recent injecting drug use: the SHARP-C study.

Ang J, Hajarizadeh B, Tillakeratne S, Dore GJ, Treloar C, Amin J, van Dyk J, Degenhardt L, Applegate T, Dunlop A, Fraser C, Conway B, Wong A, Fuchs D, Powis J, Mason K, Gane EJ, Weltman M, Read P, Martinello M, Rowe E, Baker DA, Wade A, Matthews G, Lafferty L, Lloyd A, Grebely J, Cunningham EB

The International journal on drug policy

BACKGROUND: Injecting drug use following treatment for hepatitis C virus (HCV) may result in reinfection, potentially reversing individual, and population benefits of HCV treatment. The aim of this study was to evaluate the incidence of HCV reinfection following successful direct acting antiviral (DAA) therapy among people with recent injecting drug use. METHODS: This analysis used data from an observational cohort study of people with recent injecting drug use (previous six months) following successful DAA treatment in Australia, Canada, and New Zealand. Participants were either recruited prior to commencing DAA therapy or after a documented sustained virological response (SVR). Participants were assessed three-monthly for HCV reinfection. Reinfection was defined as recurrence of virus distinct from the initial infecting strain or recurrence after confirmed cure at or after 12 weeks post-treatment. Person-time of observation and Cox proportional hazard models were used to calculate reinfection incidence and associated factors. RESULTS: Among 112 participants who contributed follow-up time at risk of reinfection (113 person-years of follow-up time), the median age was 43 years, 34 % were female, and 86 % reported injecting drug use in the month prior to enrolment. Eleven cases of reinfection were observed for an incidence of 9.7/100 person-years (95 % confidence interval [CI], 5.4-17.4) overall, 11.1/100 person-years (95 % CI, 6.1-20.0) among people who reported injecting drugs during follow-up, and 24.3/100 person-years (95 % CI, 7.8-75.3) among those who reported sharing needles/syringes during follow-up. All cases of HCV reinfection occurred among people reporting injecting drug use during the study. CONCLUSIONS: The relatively high incidence of reinfection seen in this study underscores the importance of targeted harm reduction measures and monitoring for HCV reinfections within the first year following successful treatment among people who inject drugs. Additional research into integrated models of care incorporating harm reduction and supporting reducing risk of reinfection and HCV treatment are needed.

Understanding the clinical implications of low-level viremia in ART-treated individuals.

Conway B, Tebas P, Slama L

AIDS (London, England)

CHIME: Sofosbuvir/Velpatasvir (S/V) for the Treatment of HCV Infection Among Vulnerable Inner-City Residents.

Conway B, Yi S, Truong D

Journal of viral hepatitis

The combination of Sofosbuvir/Velpatasvir(S/V) is approved for the treatment of chronic HCV infection. In registrational trials, cure rates of 95% or more were achieved when administered as one pill per day for a period of 12 weeks, regardless of genotype or disease stage. There is a need to develop and evaluate systems of care in populations excluded from clinical trials. We aim to evaluate the safety and efficacy of S/V in a prospective study of HCV-infected inner-city residents enriched for risk behaviours for non-adherence to therapy, including problematic drug use and unstable housing. Through dedicated outreach events, we identified HCV-infected patients who were not currently engaged in health care and who were eligible to receive government-funded antiviral treatment for HCV infection. We offered them the opportunity to enrol in a multidisciplinary programme of care to address medical, psychological, social, and addiction-related needs, and provide S/V therapy in this context, with enhanced supervision of adherence. We identified 222 eligible subjects, 31.5% female, median age of 47 (24-81) years. The most common genotype was 1, followed by 3 (48.2%, 38.7%) and 21.2% scored F3-F4 FibroScan scores. 55.9% have unstable housing, and 98.6% are active drug users, with the majority utilising fentanyl, followed by amphetamines (82.9%, 64.9%). HCV treatment has been started in all 222 persons within a median of 6 weeks of engagement in care. 218 persons completed treatment, one individual withdrew from the treatment, and 3 overdose deaths were documented. HCV cure was documented in 211/218 (96.8%). Virologic relapse was documented in the other 7 cases. The intent-to-treat SVR rate of HCV treatment with S/V was 211/222 (95.0%). Taken together, our data validate the development of multidisciplinary programmes such as ours to address HCV infection, yielding high rates of engagement and retention in care, promoting initiation of treatment (usually within 6 weeks) and > 97% rate of cure.

Community Pop-Up Clinic: Cascade of Care and HCV Treatment of Vancouver’s Inner-City PWID Populations.

Yi S, Wiesmann C, Truong D, Sharma S, Conway B

Journal of viral hepatitis

Elimination of HCV infection as a public health concern by the end of this decade will require a concerted effort in all target populations, including drug-users in the inner-city. Several strategies have been proposed to identify, engage and provide HCV-infected residents with antiviral therapy and maximise treatment and cure achievement. This study aims to assess the effectiveness of a multidisciplinary approach in delivering HCV treatment to people who inject drugs (PWID) within Vancouver's inner city. We have evaluated a novel approach, the Community Pop-Up Clinic, for its ability to promote access to care and uptake of HCV therapy, with additional analyses of HCV reinfection and opioid-related mortality. From January 2021 to August 2023, we evaluated 1968 individuals. 620 (31.5%) were found to carry HCV antibodies and of these, 474 (76.5%) were found to be viremic. Treatment engagement has been secured in 387 (81.6%). 326 (84.2%) have started treatment, 60 in the pre-treatment phase and 1 died of an overdose in pre-treatment. Of 326, 302 completed treatments, 18 are currently on treatment and 1 died of an overdose. Of 302 who completed treatment, 286 confirmed as cured (SVR 12), 16 are awaiting SVR 4, 2 had documented virologic relapse and 1 was reinfected. Three patients withdrew from treatment. By mITT, the cure rate is 286/288 (99.3%). We documented 2 overdose deaths over 326 PY. The data presented validates multidisciplinary programs such as ours aimed at treating HCV in inner-cities and highlights societal benefits that could be achieved including lower overdose death rates.

The challenge of normalizing vaccine behaviors in the postpandemic era.

Wiesmann C, Conway B

AIDS (London, England)

Long-term outcome in people who use drugs successfully treated for hepatitis C infection with glecaprevir/pibrentasvir.

Yi S, Truong D, Conway B

Journal of virus eradication

BACKGROUND: Several clinical trials, including the recently published the GRAND PLAN study from Vancouver Infectious Diseases Center (VIDC), have demonstrated the efficacy of hepatitis C (HCV) therapy among active drug users, including those facing significant addiction-related and social challenges. In the GRAND PLAN, we documented sustained virological response post-treatment Week12 (SVR12) in 108/117 (92.3 %) individuals (108/111 (mITT) or 97.3 % of those reaching the SVR12 timepoint) receiving an 8-week course of glecaprevir/pibrentasvir (G/P), with almost all using fentanyl and over half being unstably housed. Data on the maintenance of this favorable outcome in the long-term in such a population with a significant risk of reinfection is limited. We hypothesized that the offer of ongoing multidisciplinary care (including addiction care) after SVR12 was achieved would reduce the likelihood of loss to follow up, HCV reinfection or death and consolidate the gains achieved by initial engagement in care to diagnose and treat HCV infection. METHODS: The inception cohort for this analysis was the 108 individuals achieving a cure of HCV infection within the GRAND PLAN study. All were offered the opportunity to continue to receive care at the VIDC. This is a multidisciplinary model of care to address medical, mental health, social and addiction-related concerns on an ongoing basis. This included, if necessary, opiate agonist and safer supply therapy, usually provided by the pharmacy adjacent to our inner-city campus. Among those choosing to be retained in care, the endpoint of this analysis was loss to follow up, mortality and HCV reinfection and their correlates. Reinfection was ascertained by repeat HCV RNA testing every 6 months, more frequently if clinically indicated. RESULTS: Of the 108 individuals making up the inception cohort for this analysis, all chose to remain in care at the VIDC. We note a median age of 47 (22-75) years, 28 % female, 21.3 % identifying as indigenous, the majority with mild fibrosis (90.8 % F0-F2), slightly more than half with unstable housing. It is of note that we recorded a 20 % decrease in fentanyl users among those who were cured compared to the baseline evaluation of the overall study cohort (73.5 % vs 94.9 %, p < 0.000001). Among the cured individuals, 104 (96.3 %) remained alive, while 4 individuals died of opioid overdoses. Out of the 104 , 99 (95.2 %) remained HCV-free, while 5 (4.8 %) were re-infected. All five have recently initiated repeat HCV therapy at VIDC, 2 of whom are already documented to be cured. CONCLUSION: Among a population of vulnerable inner-city residents cured of HCV infection within a multidisciplinary program of care at the VIDC, all individuals accepted the offer to remain in long-term follow up, with a statistically significant reduction in fentanyl use over time. In the setting of an ongoing opioid crisis where 3 deaths/day are recorded in the neighborhood where the study population resides, we documented 4 deaths. Reinfections occurred at a very modest rate, with maintenance in care allowing prompt re-treatment, with a cure already being documented in 2/5 cases, with the other 3 individuals remaining on HCV therapy at the VIDC.

Updated Results from the Retrospective CREST Study on the Safety and Effectiveness of 8-Week Glecaprevir/Pibrentasvir in HCV-Infected Treatment-Naïve Patients with Compensated Cirrhosis.

Cornberg M, Hüppe D, Sarrazin C, Ahumada A, Jorquera Plaza F, Mariño Z, Otano JIU, Conway B, Myles L, Ramji A, Abergel A, Asselah T, Larrey D, Aghemo A, Andreoni M, Gasbarrini A, Lampertico P, Persico M, Villa E, Carmiel M, Chodick G, Weil C, Bhagat A, Bondin M, Butrymowicz I, Song Y, Semizarov D, Sonparote S, Llamas C, CREST Study Group

Advances in therapy

INTRODUCTION: This brief report presents updated findings from the previously published CREST study evaluating the safety and effectiveness of 8-week glecaprevir/pibrentasvir (GLE/PIB) in treatment-naïve patients with chronic hepatitis C virus (HCV) infection and compensated cirrhosis. The current study includes an additional 51 patients, presents effectiveness data stratified by additional comorbidities and comedications, and offers insights into healthcare resource utilization. METHODS: Analysis of treatment-naïve patients with HCV infection and compensated cirrhosis enrolled in the CREST study, a real-world, observational multicenter study. All enrolled patients were included in the full analysis set (FAS); the modified analysis set (MAS) excluded patients with missing SVR12 data, or who discontinued GLE/PIB for nonvirologic failure. The primary endpoint was sustained virologic response at posttreatment week 12 (SVR12) in the MAS. Safety and healthcare resource utilization were also assessed. RESULTS: The FAS included 437 patients, and the MAS 375. Overall, the results were consistent with the previously published study, with 98.9% of patients in the MAS achieving SVR12. Patients with comorbidities such as alcoholism, diabetes, and hyperlipidemia achieved SVR12 rates > 94%. High SVR12 rates were also achieved by patients receiving comedications such as anxiolytics, antidepressants, and opioid agonists. Of the 26.8% of patients with an adverse event, 1.1% had a serious adverse event, none of which were deemed related to GLE/PIB. Healthcare resource utilization varied by employment status and history of drug use. Active drug users had more physician and nurse visits than specialist visits compared with former drug users. CONCLUSION: This study provides further evidence on the safety and effectiveness of 8-week GLE/PIB, supporting the use of shorter treatment in treatment-naïve patients with Child-Pugh A cirrhosis including subgroups of interest, regardless of comorbidities and comedications observed in this population. The variable healthcare resource utilization in different patient types can help plan and resource linkage to care better, thus supporting HCV elimination efforts.

Mixed-Genotype HCV Direct Acting Antiviral Outcomes: A CANUHC Analysis.

Imsirovic H, Macphail G, Conway B, Fraser C, Borgia S, Smyth D, Wong A, Vachon ML, Webster D, Liu H, Feld J, Lee S, Cooper C, Canadian Network Undertaking against Hepatitis C (CANUHC) Cohort Investigator Team

Journal of viral hepatitis

The prevalence of mixed hepatitis C virus (HCV) genotype infection in a representative Canadian HCV cohort is reported and virological response with direct acting antiviral (DAA) treatment was evaluated. 3272 HCV-positive participants were enrolled, of which 2945 (90.0%) initiated DAA therapy. 0.8% were identified with mixed genotype infection. Overall sustained virological response (SVR) was 99.1% and did not differ based on mixed genotype status. Any historical disadvantage to achieving cure with HCV treatment in mixed genotype infection has been overcome by current DAA regimens.

A comparison of sofosbuvir/velpatasvir and glecaprevir/pibrentasvir for the treatment of hepatitis C infection among people who inject drugs.

Yi S, Truong D, Conway B

Journal of virus eradication

BACKGROUND: To eliminate hepatitis C (HCV) infection as a public health concern by 2030, there is a need to develop comprehensive programs among key populations such as people who use drugs (PWUD). Two highly effective regimens are available for initial therapy: glecaprevir/pibrentasvir (G/P) given as 3 tablets/day for 8 weeks and sofosbuvir/velpatasvir (S/V) given as 1 tablet/day for 12 weeks. Data evaluating the safety and efficacy comparing one regimen over another in a population of PWUD is limited. METHODS: Patients were identified through outreach events. Viremic patients were offered HCV treatment within a multidisciplinary program. This retrospective comparison analysis focuses on the first 120 sequential individuals who chose either treatment and in whom a definitive outcome of treatment was available between March 1, 2019 and February 29, 2024. The primary outcomes of the analysis were cure of HCV infection and its corelates, as well as safety of the individual regimens. RESULTS: We successfully identified 120 within each of the G/P and S/V treatment groups. Of those on G/P, we note 28.3 % female, 20.9 % Indigenous, 70.8 % using fentanyl, and 51.3 % with unstable housing. Of those on S/V, we note 25.8 % female, 20.8 % Indigenous, and 75 % using fentanyl and 56.7 % with unstable housing. Overall, 118 and 115 patients completed therapy on G/P and S/V, respectively. A total of 118 and 115 completed therapy on G/P and S/V, with virologic relapse documented in 3 and 2 participants on G/P and S/V, respectively. The ITT/mITT cure rates for G/P and S/V were 95.0 %/97.4 % and 94.2 %/98.3 %, respectively. There were 5 drug overdose deaths among those who initiated treatment, one on G/P and 4 on S/V. Conclusion: We have evaluated two highly effective regimens in a group of inner-city PWUD, with comparable success rates well in excess of 90 %. Our data supports the offer of both options for the treatment of PWUD with HCV infection.

GRAND PLAN: Safety and Efficacy of Glecaprevir/Pibrentasvir for the Treatment of Hepatitis C Virus Infection Among People Initially Disengaged From Health Care Who Use Drugs-A Systematic Multidisciplinary Approach.

Conway B, Yi S, Yung R, Sharma S

Open forum infectious diseases

BACKGROUND: GRAND PLAN is a prospective, open-label, phase 4 study. Based at a single center and with a single arm, GRAND PLAN evaluated the safety and efficacy of an 8-week course of glecaprevir/pibrentasvir (G/P) among active drug users with hepatitis C virus (HCV) infection in a population enriched for factors that may reduce treatment uptake and success, such as disengagement from health care and unstable housing. METHODS: Participants were ≥19 years old and actively using drugs and were confirmed viremic, noncirrhotic, and HCV treatment naive. All participants provided informed consent before any study procedures. They received G/P for 8 weeks within a multidisciplinary model of care, with daily, weekly, or monthly dispensing of medications to optimize adherence. RESULTS: We identified 117 eligible patients with a median age of 46 years (range, 22-75): 27% were female, 21.4% were Indigenous, 48.7% were unstably housed, and 95.7% were active drug users (94.9% fentanyl). One patient did not start treatment, and 4 underwent 95%. With a short course of treatment, G/P is an attractive option for this population in helping us achieve the World Health Organization's HCV objectives by 2030.

Determining reinfection rates by hepatitis C testing interval among key populations: A systematic review and meta-analysis.

Munari SC, Traeger MW, Menon V, Latham NH, Manoharan L, Luhmann N, Baggaley R, MacDonald V, Verster A, Siegfried N, Conway B, Klein M, Bruneau J, Stoové MA, Hellard ME, Doyle JS

Liver international : official journal of the International Association for the Study of the Liver

BACKGROUND & AIMS: Detecting hepatitis C virus (HCV) reinfection among key populations helps prevent ongoing transmission. This systematic review aims to determine the association between different testing intervals during post-SVR follow-up on the detection of HCV reinfection among highest risk populations. METHODS: We searched electronic databases between January 2014 and February 2023 for studies that tested individuals at risk for HCV reinfection at discrete testing intervals and reported HCV reinfection incidence among key populations. Pooled estimates of reinfection incidence were calculated by population and testing frequency using random-effects meta-analysis. RESULTS: Forty-one single-armed observational studies (9453 individuals) were included. Thirty-eight studies (8931 individuals) reported HCV reinfection incidence rate and were included in meta-analyses. The overall pooled estimate of HCV reinfection incidence rate was 4.13 per 100 per person-years (py) (95% confidence interval [CI]: 3.45-4.81). The pooled incidence estimate among people who inject drugs (PWID) was 2.84 per 100 py (95% CI: 2.19-3.50), among men who have sex with men (MSM) 7.37 per 100 py (95% CI: 5.09-9.65) and among people in custodial settings 7.23 per 100 py (95% CI: 2.13-16.59). The pooled incidence estimate for studies reporting a testing interval of ≤6 months (4.26 per 100 py; 95% CI: 2.86-5.65) was higher than studies reporting testing intervals >6 months (5.19 per 100 py; 95% CI: 3.92-6.46). CONCLUSIONS: HCV reinfection incidence was highest in studies of MSM and did not appear to change with retesting interval. Shorter testing intervals are likely to identify more reinfections, help prevent onward transmission where treatment is available and enable progress towards global HCV elimination, but additional comparative studies are required.

Reported adverse events related to use of hepatitis C virus direct-acting antivirals with opioids: 2017-2021.

Martinez A, Khan T, Dylla DE, Marcinak J, Collins M, Saget B, Conway B

Harm reduction journal

INTRODUCTION: Due to concerns over potential interactions between some hepatitis C direct-acting antivirals (DAAs) and opioids, we describe adverse event (AE) reports of concomitant use of opioids and DAAs. METHODS: AEs reported (July 28, 2017-December 31, 2021) with the administration of the DAAs glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, ledipasvir/sofosbuvir, sofosbuvir/velpatasvir/voxilaprevir, and elbasvir/grazoprevir as suspect products were downloaded from the US Food and Drug Administration AE Reporting System Public Dashboard. The number of AE reports containing opioids (fentanyl, hydrocodone, oxycodone) as co-suspect products/concomitant products were counted and summarized by severity, reporting country and whether an outcome of death was reported. Overdose AEs were counted irrespective of opioid use, and changes over time were assessed. RESULTS: In total, 40 AEs were reported for DAAs and concomitant fentanyl use, 25 (62.5%) were in the USA, 35 (87.5%) were considered serious, and 14 (35.0%) resulted in death; and 626 were reported with concomitant oxycodone/hydrocodone use, 596 (95.2%) were in the USA, 296 (47.3%) were considered serious, and 28 (4.5%) resulted in death. There were 196 overdose AEs (32 [16%] deaths) declining from 2018 (N = 56) to 2021 (N = 29). CONCLUSIONS: Treating people with hepatitis C virus (HCV) infection who use drugs is key to achieving HCV elimination. Low numbers of DAA AE reports with opioids may provide reassurance to prioritize HCV treatment in this population. These data contribute to evidence supporting the continued scale-up of DAA treatment among people who use drugs to achieve HCV elimination goals.

Assessment of Drug-Drug Interaction Risk Between Intravenous Fentanyl and the Glecaprevir/Pibrentasvir Combination Regimen in Hepatitis C Patients Using Physiologically Based Pharmacokinetic Modeling and Simulations.

Mukherjee D, Collins M, Dylla DE, Kaur J, Semizarov D, Martinez A, Conway B, Khan T, Mostafa NM

Infectious diseases and therapy

INTRODUCTION: An unsafe injection practice is one of the major contributors to new hepatitis C virus (HCV) infections; thus, people who inject drugs are a key population to prioritize to achieve HCV elimination. The introduction of highly effective and well-tolerated pangenotypic direct-acting antivirals, including glecaprevir/pibrentasvir (GLE/PIB), has revolutionized the HCV treatment landscape. Glecaprevir is a weak cytochrome P450 3A4 (CYP3A4) inhibitor, so there is the potential for drug-drug interactions (DDIs) with some opioids metabolized by CYP3A4, such as fentanyl. This study estimated the impact of GLE/PIB on the pharmacokinetics of intravenous fentanyl by building a physiologically based pharmacokinetic (PBPK) model. METHODS: A PBPK model was developed for intravenous fentanyl by incorporating published information on fentanyl metabolism, distribution, and elimination in healthy individuals. Three clinical DDI studies were used to verify DDIs within the fentanyl PBPK model. This model was integrated with a previously developed GLE/PIB PBPK model. After model validation, DDI simulations were conducted by coadministering GLE 300 mg + PIB 120 mg with a single dose of intravenous fentanyl (0.5 µg/kg). RESULTS: The predicted maximum plasma concentration ratio between GLE/PIB + fentanyl and fentanyl alone was 1.00, and the predicted area under the curve ratio was 1.04, suggesting an increase of only 4% in fentanyl exposure. CONCLUSION: The administration of a therapeutic dose of GLE/PIB has very little effect on the pharmacokinetics of intravenous fentanyl. This negligible increase would not be expected to increase the risk of fentanyl overdose beyond the inherent risks related to the amount and purity of the fentanyl received during recreational use.

Point-of-care urine tenofovir testing: making a good thing better.

Zaccarelli M, Niyongabo B, Conway B

AIDS (London, England)

Patient-Reported Outcomes During and After Hepatitis C Virus Direct-Acting Antiviral Treatment Among People Who Inject Drugs.

Cheng Q, Cunningham EB, Shih S, Amin J, Bruneau J, Artenie AA, Powis J, Litwin AH, Cooper C, Dalgard O, Hellard M, Bruggmann P, Marks P, Lacombe K, Stedman C, Read P, Hajarizadeh B, Dunlop AJ, Conway B, Feld JJ, Dore GJ, Grebely J, SIMPLIFY and D3FEAT Study Groups

Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research

OBJECTIVES: People who inject drugs (PWID) are at a high risk of hepatitis C virus (HCV) infection. HCV cure is associated with improved patient-reported outcomes (PROs), but there are little data among PWID. This study aimed to assess the change in PROs during and after HCV direct-acting antiviral (DAA) treatment. METHODS: This analysis used data from 2 clinical trials of DAA treatment in PWID. PROs assessed included health-related quality of life, social functioning, psychological distress, housing, and employment. Generalized estimating equations and group-based trajectory modeling were used to assess changes in PROs over time. RESULTS: No significant changes in the 3-level version of EQ-5D scores, EQ visual analogue scale scores, social functioning, psychological distress, and housing were observed over the 108-week study period. There was a significant increase in the proportion of participants employed (18% [95% confidence interval (CI) 12%-23%] at baseline to 28% [95% CI 19%-36%] at the end of the study). Participants were more likely to be employed at 24 weeks and 108 weeks after commencing treatment. Having stable housing increased the odds of being employed (odds ratio 1.70; 95% CI 1.00-2.90). The group-based trajectory modeling demonstrated that most outcomes remained stable during and after DAA treatment. CONCLUSIONS: Although no significant improvement was identified in health-related quality of life after HCV DAA treatment, there was a modest but significant increase in employment during study follow-up. The study findings support the need for multifaceted models of HCV care for PWID addressing a range of issues beyond HCV treatment to improve quality of life.

Real-world Evidence for Impact of Opioid Agonist Therapy on Nonfatal Overdose in Patients with Opioid Use Disorder during the COVID-19 Pandemic.

Lee K, Zhao Y, Merali T, Fraser C, Kozicky JM, Mormont MC, Conway B

Journal of addiction medicine

OBJECTIVES: The primary objectives of this study were to describe the demographics and clinical characteristics of patients who were treated with buprenorphine extended-release versus buprenorphine-naloxone sublingual tablets versus methadone in a real-world setting and to evaluate the difference in nonfatal overdose events between treatment cohorts. METHODS: This study was a retrospective chart review of patients with opioid use disorder initiating opioid agonist therapy in Canada during the outset of the COVID-19 pandemic (March 11, 2020 to October 31, 2021). Three treatment cohorts were defined by the initial prescribed opioid agonist therapy regimen: buprenorphine extended-release, buprenorphine-naloxone sublingual tablets, and methadone. Baseline characteristics, as well as treatment status, overdose events, and substance use 6 months after treatment initiation were collected using a standardized form. RESULTS: Nine clinics provided data on 379 patient cases. The incidence rate (number of events per 100 person-years) for a self-reported nonfatal overdose was 46.8 (n = 18), 19.3 (n = 10), and 1.7 (n = 1) in the methadone, buprenorphine-naloxone sublingual tablets, and buprenorphine extended-release cohorts, respectively. The risk-adjusted difference for the proportion of patients with nonfatal overdose was 8.59% (95% confidence interval, 3.10-14.08%; P = 0.0022) for methadone versus buprenorphine extended-release and 6.51% (95% confidence interval, 1.46-11.56%; P = 0.0115) for buprenorphine-naloxone sublingual tablets versus buprenorphine extended-release. CONCLUSIONS: Buprenorphine extended-release was associated with lower rates of nonfatal overdose events compared with daily opioid agonist therapy. Given the limitations of this naturalistic, retrospective design, further prospective studies are needed to validate these findings and demonstrate the potential for long-acting opioid agonist therapy in addressing the opioid crisis.

Health-related quality of life in people receiving opioid agonist treatment and treatment for hepatitis C virus infection.

Dalgard O, Litwin AH, Shibolet O, Grebely J, Nahass R, Altice FL, Conway B, Gane EJ, Luetkemeyer AF, Peng CY, Iser D, Gendrano IN, Kelly MM, Haber BA, Platt H, Puenpatom A, CO-STAR Investigators

Journal of addictive diseases

BACKGROUND: In people with chronic hepatitis C virus (HCV) infection, viral eradication is associated with improved health-related quality of life (HRQOL). OBJECTIVE: To assess changes in HRQOL among participants receiving opioid agonist therapy undergoing treatment for HCV infection. METHODS: COSTAR (NCT02251990) was a randomized, double-blind, placebo-controlled study. Adults with HCV infection on opioid agonist therapy received elbasvir (50 mg)/grazoprevir (100 mg) or placebo for 12 weeks. HRQOL was evaluated using the Medical Outcomes Study 36-Item Short Form Health Survey version 2 (SF-36v2) Acute Form. Participants remained blinded until 4 weeks after end of treatment. RESULTS: Overall, 201 participants received elbasvir/grazoprevir and 100 participants received placebo. Treatment difference mean change from baseline scores (elbasvir/grazoprevir minus placebo) indicated an improvement in HRQOL at 4 weeks after end of treatment in participants receiving elbasvir/grazoprevir versus those receiving placebo, driven by declining HRQOL in those receiving placebo and improved HRQOL in certain domains among participants receiving elbasvir/grazoprevir. Notable differences in SF-36v2 scores were evident in the general health (mean treatment difference [MTD], 6.00; 95% CI, 1.37-10.63), vitality (MTD, 6.81; 95% CI, 1.88-11.75), and mental health (MTD, 5.17; 95% CI, 0.52-9.82) domains and in the mental component summary score (mean, 2.83; 95% CI, 0.29-5.37). No notable between-treatment differences were evident at treatment weeks 4 or 12. CONCLUSION: HRQOL in patients receiving medication for opioid dependence was improved following treatment for HCV infection with elbasvir/grazoprevir, suggesting that eradication of HCV infection with direct-acting antivirals is associated with improved HRQOL. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT02251990.

COVID-19 in homeless populations: unique challenges and opportunities.

Conway B, Truong D, Wuerth K

Future Virology

Vulnerable populations, such as those in urban Vancouver, are both more susceptible to COVID-19 and less able to implement recommended...

Sofosbuvir/velpatasvir (S/V) for the treatment of chronic HCV in active drug users: the CHIME study

VIDC

Canadian Liver Meeting

CHIME Study | To meet the WHO HCV elimination goals of 2030, members of priority populations, such as people who use drugs (PWUD), must be identified and engaged in care leading to the provision of HCV therapy.

Overdose events among active drug users successfully treated for HCV: the impact of homelessness.

VIDC

Canadian Liver Meeting

Presented at the Canadian Liver Meeting. February 28- March 1, Montreal, Canada, 2020.

Glecaprevir/pibrentasvir for the treatment of hepatitis C virus infection among active drug users: the GRAND PLAN study

VIDC

Canadian Liver Meeting

GRAND PLAN Study | In order to achieve the WHO objective to eliminate HCV infection as a public health concern by 2030, short course of all oral, highly effective and well tolerated treatment regimens will be important in engaging infected active drug users.

Glecaprevir/pibrentasvir+sofosbuvir: An optimal retreatment strategy in the setting of HCV NS5A resistance

Alimohammadi A, Conway B, Yamamoto L

BMJ Case Reports CP

Some individuals do not achieve a cure of their hepatitis C virus (HCV) infection due to non-adherence or resistance associated substitution

Sofosbuvir and velpatasvir in the treatment of chronic hepatitis C

Wuerth K, Magel T, Conway B

Future Virology

Advances in hepatitis C virus (HCV) treatment led to the development of highly effective all oral direct acting antiviral regimens.

Vers l’élimination du VHC en BC : une stratégie pour s’attaquer au ‘milieu désordonne’

VIDC

International Viral Hepatitis Elimination

In the absence of a comprehensive provincial or federal action plan to address the HCV pandemic in British Columbia, Canada, the major challenge is to move infected patients through the cascade of care towards treatment initiation in an efficient way.

Efficacité du sofosbuvir/velpatasvir et de l’elbasvir/grazoprévir pour le traitement de l’infection par le VHC de génotype 1 dans une cohorte réelle avec de nombreuses personnes qui consomment des drogues (PWUD)

VIDC

American Association for the Study of Liver Diseases

The purpose of this analysis was to evaluate the effectiveness of two recommended treatment regimens for HCV genotype 1 infection, sofobuvir/velpatasvir (SOF/VEL) and elbasvir/grazoprevir (EBR/GZR), in a real-world vulnerable inner city population.

Real-world efficacy of salvage therapies for the treatment of chronic hepatitis C virus infection in treatment experienced people who inject drugs (PWID)

VIDC

American Association for the Study of Liver Diseases

The aim of this analysis was to evaluate the efficacy of sofosbuvir/velpatasvir/voxipalrevir (SVV) and glecaprevir/pibrentavir + sofosbuvir (GPS) among vulnerable populations such as PWID.

Suivi à long terme des personnes qui consomment des drogues (PWUD) suite à un traitement réussi contre le VHC : habitudes de consommation de drogues et maintien de la guérison

VIDC

American Association for the Study of Liver Diseases

This analysis was conducted to determine the benefits of a dedicated long-term multidisciplinary program of care in a group of people who use drugs (PWUD) having successfully competed HCV therapy.

Low rate of reinfection among a cohort of people who use drugs successfully treated for hepatitis C infection in Vancouver, Canada

Holeksa J, Magel T, Alimohammadi A, Thiam A, Yung R, Chu L, Truong D, Conway B

International Journal of Drug Policy

Concerns about reinfection may be limiting HCV treatment uptake among people who use drugs (PWUD), with rates of 17.1/100 person-years in...

Preliminary results from a novel model of HCV care in OST clinics: find 50

VIDC

Western Canada Addiction Forum

Presented at the Western Canada Addiction Forum, May 3-5, Kelowna, Canada, 2019.

Diagnosis and treatment of hepatitis C virus infection: a tool for engagement with people who inject

Alimohammadi A, Holeksa J, Parsons R, Yung R, Amiri N, Truong D, Conway B

Canadian Liver Journal

Vancouver’s Downtown Eastside (DTES) faces the interrelated challenges of poverty, homelessness, mental health, addiction, and medical issue

Real-world Efficacy of Direct-Acting Antiviral Therapy for HCV Infection Affecting People Who Inject Drugs Delivered in a Multidisciplinary Setting

Arshia Alimohammadi, Julie Holeksa, Astou Thiam, David Truong, Brian Conway

Open Forum Infectious Diseases

A VIDC study evaluating real-world direct-acting antiviral treatment outcomes among people who inject drugs within a multidisciplinary model of care.