Research Papers

@article{S2020,
title = {Eliminating Structural Barriers: The Impact of Unrestricted Access on Hepatitis C Treatment Uptake Among People Living With Human Immunodeficiency Virus},
author = {Saeed S and Strumpf E and Moodie EEM and Wong L and Cox J and Walmsley S and Tyndall M and Cooper C and Conway B and Hull M and Martel-Laferriere V and Gill MJ and Wong A and Vachon ML and Klein MB and for the Canadian Co-Infection Cohort Study Investigators},
url = {https://pubmed.ncbi.nlm.nih.gov/31504327/},
doi = {10.1093/cid/ciz833},
year = {2020},
date = {2020-07-11},
journal = {Clinical Infectious Diseases},
abstract = {Background: High costs of direct-acting antivirals (DAAs) have led health-care insurers to limit access worldwide. Using a natural experiment, we evaluated the impact of removing fibrosis stage restrictions on hepatitis C (HCV) treatment initiation rates among people living with human immunodeficiency virus (HIV), and then examined who was left to be treated.

Methods: Using data from the Canadian HIV-HCV Coinfection Cohort, we applied a difference-in-differences approach. Changes in treatment initiation rates following the removal of fibrosis stage restrictions were assessed using a negative binomial regression with generalized estimating equations. The policy change was then specifically assessed among people who inject drugs (PWID). We then identified the characteristics of participants who remained to be treated using a modified Poisson regression.

Results: Between 2010-2018, there were a total of 585 HCV initiations among 1130 eligible participants. After removing fibrosis stage restrictions, DAA initiations increased by 1.8-fold (95% confidence interval [CI] 1.3-2.4) controlling for time-invariant differences and secular trends. Among PWID the impact appeared even stronger, with an adjusted incidence rate ratio of 3.6 (95% CI 1.8-7.4). However, this increased treatment uptake was not sustained. At 1 year following universal access, treatment rates declined to 0.8 (95% CI .5-1.1). Marginalized participants (PWID and those of indigenous ethnicity) and those disengaged from care were more likely to remain HCV RNA positive.

Conclusions: After the removal of fibrosis restrictions, HCV treatment initiations nearly doubled immediately, but this treatment rate was not sustained. To meet the World Health Organization elimination targets, the minimization of structural barriers and adoption of tailored interventions are needed to engage and treat all vulnerable populations.},
keywords = {Direct acting antivirals (DAAs), HIV-HCV co-infection, People who inject drugs, Quasi-experimental methods, Unrestricted access},
pubstate = {published},
tppubtype = {article}
}

@article{R2019,
title = {Variation in hepatitis C virus treatment uptake between Canadian centres in the era of direct-acting antivirals},
author = {Nitulescu R and Young J and Saeed S and Cooper C and Cox J and Martel-Laferriere V and Hull M and Walmsley S and Tyndall MW and Wong A and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/30594080/},
doi = {10.1016/j.drugpo.2018.08.012},
year = {2019},
date = {2019-03-01},
journal = {The International Journal on Drug Policy},
abstract = {Background: Patients co-infected with HIV and hepatitis C virus (HCV) are a priority target for HCV treatment. The simplicity and efficacy of direct-acting antivirals (DAA) should help overcome patient, provider, and structural barriers to scaling up treatment.

Methods: We estimated between-centre variation in DAA treatment uptake among 1734 patients enrolled at the 18 centres of the Canadian Co-Infection Cohort-a prospective cohort of adults co-infected with HIV and HCV. We then compared this variation to that observed during the interferon era. Time to treatment uptake was modeled using a Weibull time-to-event model adjusting for centre and patient characteristics thought to have an impact on treatment initiation in the DAA era.

Results: At the time of administrative censoring (December 31, 2016), 981 cohort participants were eligible for second-generation DAA therapy (HCV RNA positive after November 21, 2013) of whom 278 initiated DAAs (16 patients per 100 person-years). Patients with low monthly income, Indigenous ethnicity, recent injection drug use, HCV genotype 3, or unknown HCV genotype were less likely to start treatment. After adjusting for patient characteristics, the estimated between-centre variance (σ2) was 0.29 (95% credible interval [CrI]: 0.09-0.89), considerably lower than during the interferon era (σ2 = 0.87, 95% CrI: 0.49-1.5). This between-centre variance was further reduced by the addition of centre-level effects for jurisdiction (σ2 = 0.15, 95% CrI: 0.02-0.60).

Conclusion: Much of the variation in treatment uptake between centres can now be attributed to regional differences. This suggests that after the introduction of DAAs, treatment barriers have shifted towards prescribing and reimbursement restrictions based on liver fibrosis, which vary by jurisdiction. The removal of these restrictions, however, will need to be paired with strategies to overcome patient-level barriers, which continue to prevent marginalized people and active substance users from accessing treatment.},
keywords = {Direct acting antivirals (DAAs), Disparities, HIV-HCV co-infection, Treatment barriers, Treatment uptake},
pubstate = {published},
tppubtype = {article}
}

@article{C2019,
title = {Direct-Acting Antiviral Treatment Failure Among Hepatitis C and HIV-Coinfected Patients in Clinical Care},
author = {Rossi C and Young J and Martel-Laferriere V and Walmsley S and Cooper C and Wong A and Gill MJ and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/30882016/},
doi = {10.1093/ofid/ofz055},
year = {2019},
date = {2019-02-13},
journal = {Open Forum Infectious Diseases},
abstract = {Background: There are limited data on the real-world effectiveness of direct-acting antiviral (DAA) treatment in patients coinfected with hepatitis C virus (HCV) and HIV-a population with complex challenges including ongoing substance use, cirrhosis, and other comorbidities. We assessed how patient characteristics and the appropriateness of HCV regimen selection according to guidelines affect treatment outcomes in coinfected patients.

Methods: We included all patients who initiated DAA treatment between November 2013 and July 2017 in the Canadian Co-Infection Cohort. Sustained virologic response (SVR) was defined as an undetectable HCV RNA measured between 10 and 18 weeks post-treatment. We defined treatment failure as virologic failure, relapse, or death without achieving SVR. Bayesian logistic regression was used to estimate the posterior odds ratios (ORs) associated with patient demographic, clinical, and treatment-related risk factors for treatment failure.

Results: Two hundred ninety-five patients initiated DAAs; 31% were treatment-experienced, 29% cirrhotic, and 80% HCV genotype 1. Overall, 92% achieved SVR (263 of 286, 9 unknown), with the highest rates in females (97%) and lowest in cirrhotics (88%) and high-frequency injection drug users (89%). Many patients (38%) were prescribed regimens that were outside current clinical guidelines. This did not appreciably increase the risk of treatment failure-particularly in patients with genotype 1 (prior odds ratio [OR], 1.5; 95% credible interval [CrI], 0.38-6.0; posterior OR, 1.0; 95% CrI, 0.40-2.5).

Conclusions: DAAs were more effective than anticipated in a diverse, real-world coinfected cohort, despite the use of off-label, less efficacious regimens. High-frequency injection drug use and cirrhosis were associated with an increased risk of failure.},
keywords = {Direct acting antivirals (DAAs), Hepatitis C virus, HIV-HCV co-infection, Treatment failure, Treatment guidelines},
pubstate = {published},
tppubtype = {article}
}

@article{S2018,
title = {Real-world impact of direct acting antiviral therapy on health-related quality of life in HIV/Hepatitis C co-infected individuals},
author = {Saeed S and Moodie EEM and Strumpf E and Gill MJ and Wong A and Cooper C and Walmsley S and Hull M and Martel-Laferrière V and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/30141236/},
doi = {10.1111/jvh.12985},
year = {2018},
date = {2018-12-01},
journal = {Journal of Viral Hepatitis},
abstract = {Clinical trial results of direct acting antivirals (DAAs) for the treatment of hepatitis C virus (HCV) have shown improvements in health-related quality of life (HR-QoL). However, the extent to which these results are broadly generalizable to real-world settings is unknown. We investigated the real-world impact of oral DAA therapy on HR-QoL among individuals coinfected with HIV/HCV. We used data from the Canadian HIV/HCV Co-Infection Cohort Study that prospectively follows 1795 participants from 18 centres. Since 2007, clinical, lifestyle, and HR-QoL data have been collected biannually through self-administered questionnaires and chart review. HR-QoL was measured using the EQ-5D instrument. Participants initiating oral DAAs, having at least one visit before treatment initiation and at least one visit after DAA treatment response was ascertained, were included. Successful treatment response was defined as a sustained viral response (SVR). Segmented multivariate linear mixed models were used to evaluate the impact of SVR on HR-QoL, controlling for pretreatment trends. 227 participants met our eligibility criteria, 93% of whom achieved SVR. Before treatment, the EQ-5D utility index decreased 0.6 percentage-point/y (95% CI, -0.9, -0.3) and health state was constant over time. The immediate effect of SVR resulted in an increase of 2.3-units (-0.1, 4.7) in patients' health state and 2.0 percentage-point increase (-0.2, 4.0) in utility index. Health state continued to increase post-SVR by 1.4 units/y (-0.9, 3.7), while utility trends post-SVR plateaued over the observation period. Overall using real-world data, we found modest improvements in HR-QoL following SVR, compared to previously published clinical trials.},
keywords = {Direct acting antivirals (DAAs), EQ-5D, Health-related QOL, Hepatitis C virus, HIV},
pubstate = {published},
tppubtype = {article}
}

@article{N2018,
title = {Previous incarceration impacts access to hepatitis C virus (HCV) treatment among HIV-HCV co-infected patients in Canada},
author = {Kronfli N and Nitulescu R and Cox J and Moodie E and Wong A and Cooper C and Gill J and Walmsley S and Martel-Leferriere V and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/30460791/},
doi = {10.1002/jia2.25197},
year = {2018},
date = {2018-11-01},
journal = {Journal of the International AIDS Society},
abstract = {Introduction: The prevalence of hepatitis C virus (HCV) is far higher in prison settings than in the general population; thus, micro-elimination strategies must target people in prison to eliminate HCV. We aimed to examine incarceration patterns and determine whether incarceration impacts HCV treatment uptake among Canadian HIV-HCV co-infected individuals in the direct-acting antiviral (DAA) era.

Methods: The Canadian Co-Infection Cohort prospectively follows HIV-HCV co-infected people from 18 centres. HCV RNA-positive participants with available baseline information on incarceration history were included and followed from 21 November 2013 (when second-generation DAAs were approved by Health Canada) until 30 June 2017. A Cox proportional hazards model was used to assess the effect of time-updated incarceration status on time to treatment uptake, adjusting for patient-level characteristics known to be associated with treatment uptake in the DAA era.

Results: Overall, 1433 participants (1032/72% men) were included; 67% had a history of incarceration and 39% were re-incarcerated at least once. Compared to those never incarcerated, previously incarcerated participants were more likely to be Indigenous, earn <$1500 CAD/month, report current or past injection drug use and have poorly controlled HIV. There were 339 second-generation DAA treatment initiations during follow-up (18/100 person-years). Overall, 48% of participants never incarcerated were treated (27/100 person-years) compared to only 31% of previously incarcerated participants (15/100 person-years). Sustained virologic response (SVR) rates at 12 weeks were 95% and 92% respectively. After adjusting for other factors, participants with a history of incarceration (adjusted hazard ratio (aHR): 0.7, 95% CI: 0.5 to 0.9) were less likely to initiate treatment, as were those with a monthly income <$1500 (aHR: 0.7, 95% CI: 0.5 to 0.9) or who reported current injection drug use (aHR: 0.7, 95% CI: 0.4 to 1.0). Participants with undetectable HIV RNA (aHR: 2.1, 95% CI: 1.6 to 2.9) or significant fibrosis (aHR: 1.5, 95% CI: 1.2 to 1.9) were more likely to initiate treatment.

Conclusions: The majority of HIV-HCV co-infected persons had a history of incarceration. Those previously incarcerated were 30% less likely to access treatment in the DAA era even after accounting for several patient-level characteristics. With SVR rates above 90%, HCV elimination may be possible if treatment is expanded for this vulnerable and neglected group.},
keywords = {Direct acting antivirals (DAAs), Disparities, HCV Elimination, HIV-HCV co-infection, Micro-eliminiation, People in prison},
pubstate = {published},
tppubtype = {article}
}

@article{S2017,
title = {Disparities in direct acting antivirals uptake in HIV-hepatitis C co-infected populations in Canada},
author = {Saeed S and Strumpf EC and Moodie EEM and Young J and Nitulescu R and Cox J and Wong A and Walmsely S and Cooper C and Vachon ML and Martel-Laferriere V and Hull M and Conway B and Klein MB},
url = {https://pubmed.ncbi.nlm.nih.gov/29116684/},
doi = {10.1002/jia2.25013},
year = {2017},
date = {2017-11-01},
journal = {Journal of the International AIDS Society},
abstract = {Background: Direct acting antivirals (DAAs) have revolutionized hepatitis C (HCV) treatment with >90% cure rates even in real-world studies, giving hope that HCV can be eliminated. However, for DAAs to have a population-level impact on the burden of HCV disease, treatment uptake needs to be expanded. We investigated temporal trends in HCV treatment uptake and evaluated factors associated with second-generation DAA initiation and efficacy among key HIV-HCV co-infected populations in Canada.

Methods: The Canadian HIV-HCV Co-Infection Cohort Study prospectively follows 1699 participants from 18 centres. Among HCV RNA+ participants, we determined the incidence of HCV treatment initiation per year overall and by key populations between 2007 and 2015. Key populations were based on World Health Organization (WHO) guidelines including: people who actively inject drugs (PWID) (reporting injection drug use, last 6 months); Indigenous people; women and men who have sex with men (MSM). Multivariate Cox models were used to estimate adjusted hazard ratios (aHR) and 2-year probability of initiating second-generation DAAs for each of the key populations.

Results: Overall, HCV treatment initiation rates increased from 8 (95% CI, 6-11) /100 person-years in 2013 to 28 (95% CI, 23-33) /100 person-years in 2015. Among 911 HCV RNA + participants, there were 202 second-generation DAA initiations (93% with interferon-free regimens). After adjustment (aHR, 95% CI), active PWID (0.60, 0.38-0.94 compared to people not injecting drugs) and more generally, people with lower income (<$18 000 CAD/year) (0.50, 0.35, 0.71) were less likely to initiate treatment. Conversely, MSM were more likely to initiate 1.95 (1.33, 2.86) compared to heterosexual men. In our cohort, the population profile with the lowest 2-year probability of initiating DAAs was Indigenous, women who inject drugs (5%, 95% CI 3-8%). Not having any of these risk factors resulted in a 35% (95% CI 32-38%) probability of initiating DAA treatment. Sustained virologic response (SVR) rates were >82% in all key populations.

Conclusion: While treatment uptake has increased with the availability of second-generation DAAs, marginalized populations, already engaged in care, are still failing to access treatment. Targeted strategies to address barriers are needed to avoid further health inequities and to maximize the public health impact of DAAs.},
keywords = {Direct acting antivirals (DAAs), Disparities, HIV-HCV co-infection, Indigenous peoples, Men who have sex with men (MSM), People who inject drug (PWID), Women},
pubstate = {published},
tppubtype = {article}
}