International Journal of Nursing Studies Advances 3 (2021) 100029

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International Journal of Nursing Studies Advances

journal homepage: www.elsevier.com/locate/ijnsa

Adherence and sustained virologic response among vulnerable

people initiating an hepatitis C treatment at a nurse-led clinic: A
non-experimental prospective cohort study based on clinical
records
Myriam Gagné a,∗, Isabelle Têtu b, Jean-Pierre Grégoire c,d, Jocelyne Moisan c,d
a
Unity Health Toronto (St. Michael’s Hospital), fully affiliated with the University of Toronto, 30, Bond St. (Room Donnelly 6-099), Toronto M5B
1W8, ON, Canada
b
Clinique de solidarité SABSA, Québec City, QC, Canada
c
Population Health and Optimal Health Practices Research Unit, CHU de Québec–Université Laval Research Center, Québec City, QC, Canada
d
Faculty of Pharmacy, Université Laval, Québec City, QC, Canada

a r t i c l e i n f o a b s t r a c t

Keywords: Background: There is a need to develop specific care route for vulnerable people with hepatitis C
Interprofessional relations virus.
Medication adherence
Nurse-led clinic Objective: At a nurse-led clinic, we aimed to: (1) report the prevalence of patients initiating an
Street drugs hepatitis C treatment who (a) achieved sustained virologic response and (b) were adherent to their
Substance-related disorders treatment; and (2) explore factors associated with adherence and sustained virologic response.
Sustained virologic response
Design: A clinical record-based prospective cohort study.
Setting: A community-based nurse-led clinic coordinating outreach services for people with hep-
atitis C virus in Québec City, Québec, Canada.
Population: All patients initiating an hepatitis C treatment at the nurse-led clinic from January 1,
2012 to December 31, 2017 (end of data collection).
Methods: Patients were followed from the day they initiated their hepatitis C treatment, up to
24 weeks after the end of the treatment. Sustained virologic response was achieved if hepatitis C
virus ribonucleic acid (RNA) was undetectable or below the lower limit of quantification at week
12 or later. Patients who reported hepatitis C treatment completion without missing any doses
were considered adherent. Factors associated with adherence and sustained virologic response
were identified using adjusted prevalence ratios.
Results: A total of 171 patients infected with hepatitis C virus (women: n = 51, 30%; criminal
record: n = 102, 60%; substance addiction: n = 99, 58%) initiated an hepatitis C treatment at the
nurse-led clinic. Overall, 126/171 (74%) patients were adherent. Patients using illicit drugs were
less likely to be adherent (adjusted prevalence ratio 0.77, 95% confidence interval 0.67–0.89).
Among 156/171 (91%) patients with an hepatitis C virus RNA test post-treatment, 96% (n = 149)
achieved sustained virologic response. Patients who were less likely to achieve sustained virologic
response were those who were non-adherent (adjusted prevalence ratio 0.81, 95% confidence

∗
Corresponding author.
E-mail addresses: Myriam.Gagne@unityhealth.to (M. Gagné), Isabelle.tetu.1@ulaval.ca (I. Têtu), Jean-Pierre.Gregoire@pha.ulaval.ca (J.-P. Gré-
goire), Jocelyne.Moisan@pha.ulaval.ca (J. Moisan).

https://doi.org/10.1016/j.ijnsa.2021.100029
Received 18 November 2020; Received in revised form 15 April 2021; Accepted 22 April 2021
2666-142X/© 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license
(http://creativecommons.org/licenses/by/4.0/)
M. Gagné, I. Têtu, J.-P. Grégoire et al. International Journal of Nursing Studies Advances 3 (2021) 100029

interval 0.68–0.98) or who had a criminal record (adjusted prevalence ratio 0.87, 95% confidence
interval 0.79–0.97).
Conclusions: A nurse-led clinic could fill an important gap in hepatitis C health services targeted
at vulnerable people in a community setting, to drive adherence and achievement of sustained
virologic response.

1. Introduction

Hepatitis C virus triggers a global pandemic, with 71 million people infected worldwide (The Polaris Observatory HCV Collabo-
rators, 2017). About 75–85% of patients infected with hepatitis C virus will progress to chronic infection (Chen and Morgan, 2006).
Over the years, chronic hepatitis C virus infection will slowly and progressively damage the liver, placing people at an increased risk
of liver cirrhosis, hepatocellular carcinoma, liver failure, and deaths from hepatitis C (Axley et al., 2018; de Oliveria Andrade et al.,
2009; Stanaway et al., 2016).
Evidence shows that anti-hepatitis C virus treatment can cure hepatitis C virus infection in a majority of patients in 8–12 weeks
(American Association for the Study of Liver Diseases, Infectious Diseases Society of America, 2019; Miller et al., 2014; Shah et al.,
2018). Hence, the primary goal of chronic hepatitis C treatment is to eradicate the virus, termed as sustained virologic response, i.e.
absence of viremia 12 weeks after the end of treatment (Jacobson et al., 2012). Sustained virologic response is associated with a
75–90% reduced risk of hepatocellular carcinoma, a 80–97% decreased risk of liver-related mortality, and a 70–90% lower risk of
overall mortality (Smith-Palmer et al., 2015).
Antiviral therapy should be considered in all patients with chronic hepatitis C (Backus et al., 2018). Given the improved efficacy,
tolerability, and safety of interferon-­free over interferon-based regimens with ribavirin (Feld et al., 2015; McHutchison et al., 2009;
Suwanthawornkul et al., 2015; Zeuzem et al., 2018), interferon­free regimens are now recommended (Shah et al., 2018). Several
direct-acting antiviral agent regimens, with or without ribavirin, have been approved in Canada and elsewhere (American Associa-
tion for the Study of Liver Diseases, Infectious Diseases Society of America, 2019; Miller et al., 2014; Shah et al., 2018). Selection
of treatment regimens is dependent on various factors, including: previous hepatitis C treatment, liver disease stage, specific comor-
bidities (e.g. chronic kidney disease, decompensated cirrhosis, post­liver transplantation, hepatitis B coinfection); hepatitis C virus
genotype, viral load, and resistance testing (to determine whether adding ribavirin should be considered); and factors accelerating
disease progression (Shah et al., 2018). Number of pills per day and duration of treatment should also be considered when selecting
treatment regimens (Shah et al., 2018).
In high-income countries, up to 90% of vulnerable people (e.g. those experiencing imprisonment or substance use disorders) are
infected with hepatitis C virus (Aldridge et al., 2018). Vulnerable people are commonly excluded from mainstream society as they
experience several barriers to treatment engagement and adherence (Luchenski et al., 2018). As a result, they are more likely to
experience poor health outcomes (Lewer et al., 2019) and quality of life (Gentil et al., 2019; Lewer et al., 2019). In patients infected
with hepatitis C virus, high-drinking and substance addiction have been reported as factors delaying treatment uptake (Socias et al.,
2019). Hence, there is a need to develop specific care route to engage the most vulnerable and excluded populations in their hepatitis
C care (Luchenski et al., 2018; Popping et al., 2019). Actual interventions, however, have been insufficient to effectively prevent the
transmission of HCV among vulnerable people (Larney et al., 2017; Popping et al., 2019).
A nurse-led model of care could facilitate access to evidence-based hepatitis C treatments among those at high risk of sexually
transmitted and blood-borne infections, including vulnerable people (Richmond et al., 2020). In a nurse-led approach to care, nurses
deliver holistic patient-centered care and consolidate a network of outreach services for vulnerable people, connecting them with gas-
troenterologists and infectious disease specialists, as well as with other allied healthcare professionals (e.g. pharmacists, nutritionists,
outreach workers). Although a nurse-led model of care has been reported to help achieve sustained virologic response among prison-
ers (Lloyd et al., 2013; Papaluca et al., 2019; Perrett, 2011), it has provided inconclusive results in a community setting (Lewis et al.,
2016). Accordingly, we conducted this study with the objective of calculating the prevalence of patients who achieved sustained
virologic response after initiating an hepatitis C treatment at a community-based nurse-led clinic (primary objective). Our secondary
objectives included: to assess the prevalence of patients who were adherent to their prescribed hepatitis C treatment; and to explore
factors associated with treatment adherence and achievement of sustained virologic response.

2. Methods

We herein follow the STROBE and RECORD recommendations for reporting of observational non-experimental studies
(Benchimol et al., 2015; Vandenbroucke et al., 2007) (Supplementary Material 1).

2.1. Study design, setting, and population

We conducted a non-experimental prospective cohort study in which we abstracted medical records of all individuals who initiated
an hepatitis C treatment at the Clinique de solidarité SABSA, a nurse-led clinic located in Québec City, Québec, Canada, from January
1st, 2012 (date at which hepatitis C treatment started at this nurse-led clinic) to December 31st, 2017 (end of data collection). Co-
author IT had full access to the database population used to create the study population. The day of initiation of the hepatitis C

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M. Gagné, I. Têtu, J.-P. Grégoire et al. International Journal of Nursing Studies Advances 3 (2021) 100029

treatment at the nurse-led clinic marked patients’ entry into the cohort. Standard follow-up visits at the clinic were scheduled at
week 1, 2, and 4 after treatment initiation. Follow-up was completed 24 weeks after the end of treatment. A detailed description of
healthcare services provided at the clinic is provided as Supplementary Material 2.
The present study was approved by the CHU de Québec Research Center–Université Laval Institutional Ethics Committee (2017-
3618, 2016-2017-26 MP). The Ethics Committee did not require researcher to obtain informed consent from individuals whose data
were abstracted for the present study.

2.2. Variables and measurements

An array of variables was abstracted from the patients’ records by co-author IT with help of a research assistant (the full list
of variables can be found in Supplementary Material 3). We abstracted the following information recorded prior to treatment initi-
ation: diagnostic date, hepatitis C virus genotype and infection source. We also abstracted various clinical parameters (e.g. alanine
aminotransferase; gamma-glutamyl transpeptidase; and liver fibrosis, categorized either as absent/mild, moderate, severe, or advanced)
(de Ledinghen et al., 2006) recorded at hepatitis C treatment initiation. We abstracted data on comorbid physical and mental health
problems, patients’ sociodemographic characteristics (e.g. sex; highest attained level of education; and monthly income), self-reported
alcohol consumption, current smoking status, and history of recent illicit drug use. Finally, we abstracted the prescribed hepatitis C
treatment and its duration (e.g. 8, 12, 24 weeks).
From clinical records, we assessed whether patients had missed at least one dose and whether they had taken the prescribed
hepatitis C treatment until the last prescribed dose. We considered patients who reported treatment completion without missing
any doses as adherent. Patients for whom information on missing doses or treatment completion was lacking were considered as
non-adherent.
For the period prior to treatment initiation, the treatment period, and the 12-week period following the end of the treatment, we
abstracted data on patients’ health services utilization, including the number of encounters with a nurse, a pharmacist, an outreach
worker or a gastroenterologist.
We recorded whether sustained virologic response was achieved 12 weeks after the end of treatment (primary outcome). Sustained
virologic response was considered achieved if hepatitis C virus ribonucleic acid (RNA) was undetectable or below the lower limit of
quantification at week 12 (Jacobson et al., 2012). Patients for whom no information on sustained virologic response was available at
week 12 but who achieved sustained virologic response at week 24 were considered as having achieved sustained virologic response
at week 12. Those for whom there was no information on sustained virologic response were deemed not having achieved sustained
virologic response.
The clinic’s nurse partitioner (co-author IT) was the only research team member to have access to clinical records and, therefore,
was also the only one in charge of data abstraction. Once completed, all data abstraction forms were checked for reliability by another
researcher. Observed invalid, extreme, missing or out-of-range values were reported to co-author IT in charge of data abstraction for
additional check. If needed, errors were corrected.

2.3. Statistical analyses

All statistical analyses were performed using SAS (Cary, NC, USA). Patients’ characteristics were described using frequency dis-
tributions, as well as means and standard deviations. Among patients initiating an hepatitis C treatment at the nurse-led clinic, we
calculated the prevalence of patients who achieved sustained virologic response and the prevalence of patients who were adherent
to the prescribed hepatitis C treatment. A statistician performed univariate regression analyses of the association between study
outcomes and each of the independent variables. Variables statistically significant at the 20% level were grouped and a reduced
multivariate model was obtained by removing one by one variables not statistically significant at the 5% level of significance. The
final multivariate model was fitted using a working-Poisson regression, allowing us to present adjusted prevalence ratios, with asso-
ciated 95% confidence intervals. Similar analyses were conducted to estimate the association between treatment adherence and the
independent variables. Additional details regarding our statistical analyses are provided as Supplementary Material 4.

3. Results

3.1. Flow of patients initiating an hepatitis C treatment at the nurse-led clinic

From January 1st, 2012 to December 31st, 2017, 171 patients initiated an hepatitis C treatment at the nurse-led clinic. All were
included in our analyses. Two patients died from an overdose during the treatment period and 158/169 (93.5%) met a nurse at the
end of their treatment. One patient died from an overdose during the 12 weeks that followed. A total of 136/168 patients (81.0%)
attended the visit scheduled at week 12 and 136/168 (81.0%) attended the last visit scheduled at week 24. Detailed reasons for
missing appointments are provided in Fig. 1.

3.2. Characteristics of patients initiating an hepatitis C treatment

Among the 171 patients recruited in this cohort, 120 (70.2%) were male, 120 (70.2%) had less than a college or a university
degree, and 95 (55.6%) earned less than US$750 (CA$1,000) per month. About 60% of patients (n = 102) had a criminal record
(Table 1).

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M. Gagné, I. Têtu, J.-P. Grégoire et al. International Journal of Nursing Studies Advances 3 (2021) 100029

Fig. 1. Flowchart of selected patients throughout the study.

As shown in Table 2, about half of patients were overweight or obese (n = 90, 52.6%). About 80% of individuals had at least one
comorbid mental health problem, the most common being substance addiction (n = 99, 57.9%). Illicit injection drug use in the past
30 days was self-reported by 37 patients (21.6%), with 25 and 19 patients reporting having injected cocaine and opioid, respectively
(Table 3). About 40% of patients (n = 68) reported recent use of illicit non-injection drugs such as amphetamine (n = 30) and cannabis
(n = 46).

3.3. Characteristics of hepatitis C treatments

A total of 56 patients (32.7%) have had a prior hepatitis C treatment before entering the cohort. These patients were seeking
another treatment either due to prior treatment failure (n = 50, 89.2%) or due to hepatitis C virus re-infection (n = 6, 10.7%).
Patients (n = 166, 97.1%) were mostly prescribed the hepatitis C drug treatment by a gastroenterologist. Two-thirds of patients
(n = 106, 62.0%) were prescribed a direct-acting antiviral without ribavirin (Supplementary Material 5). While 133 patients (77.8%)
were treated for 8 or 12 weeks, 8 patients (4.7%) had a treatment duration of 48 weeks.

3.4. Adherence to the hepatitis C treatment

Due to adverse reactions, physicians prescribed hepatitis C treatment discontinuation for eight patients. A total of 158 patients
attended the visit scheduled at the end of the hepatitis C treatment (hence, 6 patients [3.5%] were deemed to be non-adherent due
to missing information for this outcome in their record). Among these 158 patients, 93% (n = 147) reported having completed the
treatment and 126 (85.7%) also reported having taken all prescribed doses. These 126 patients (73.7% of the cohort) were considered
as adherent to their prescribed treatment.

3.5. Characteristics associated with adherence to the hepatitis C treatment

Results of univariate regression analyses of the association between treatment adherence and each of the independent variables
are presented as Supplementary Material 6. Multivariate analyses showed that patients reporting a recent use of illicit drugs were
less likely to be adherent (recent use vs. non-use of illicit drugs: adjusted prevalence ratio 0.77, 95% confidence interval 0.67–0.89).
Patients who were prescribed an hepatitis C treatment length of 48 weeks (vs. 8 or 12 weeks) were also less likely to be adherent to
their hepatitis C treatment (adjusted prevalence ratio 0.29, 95% confidence interval 0.09–0.94).

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Table 1
Sociodemographic characteristics of patients at treatment initiation (N = 171).

Characteristics N (%)

Sex
Male 120 (70.2%)
Female 51 (29.8%)
Sexual orientation
Heterosexual 165 (96.5%)
Other 6 (3.5%)
Age (years)
22 to 45: quantile 1 45 (26.3%)
46 to 52: quantile 2 47 (27.5%)
53 to 59: quantile 3 39 (22.8%)
60 to 75: quantile 4 40 (23.4%)
Country of birth
Canada 162 (94.7%)
Other 9 (5.3%)
Marital status
Single 109 (63.7%)
In relationship 62 (36.3%)
Residential status
Housed 159 (93.0%)
Homeless (including shelters and transitional housing) 12 (7.0%)
Place of residence
Québec City, La Cité-Limoilou district (where SABSA is located) 91 (53.2%)
Québec City, any other district 41 (24.0%)
Outside Québec City, but within the Capitale-Nationale administrative region 13 (7.6%)
Outside the Capitale-Nationale administrative region 26 (15.2%)
Highest attained level of education
Elementary school 61 (35.7%)
High school diploma 40 (23.4%)
Diploma of vocational studies 19 (11.1%)
College degree 24 (14.0%)
≥Bachelor’s degree 10 (5.9%)
Missing data 17 (9.9%)
Primary occupation
Work or study 59 (34.5%)
Retired 15 (8.8%)
Unemployed 97 (56.7%)
Monthly incomea
From US$375 to US$749 95 (55.6%)
≥US$750 75 (43.9%)
Missing data 1 (0.5%)
Medication insurance coverage
Public 139 (81.3%)
Private 32 (18.7%)
Had a criminal record
No 69 (40.4%)
Yes 102 (59.6%)
a
Data on monthly income were collected in Canadian dollars: As of February 12, 2020, CA$ 1 =
US$ 0.753761.

3.6. Health services used during the treatment period

Prior to and during the hepatitis C treatment period, all patients were seen by a nurse (Table 4). Nearly all patients (n = 163, 95.3%)
met a gastroenterologist prior to initiating the treatment, while less than half of patients (n = 71, 44.9%) met a gastroenterologist
during the treatment period. During the treatment period, about half of patients attended more visits at the clinic than what was
scheduled (43.0%).

3.7. Sustained virologic response

Among the 171 patients who initiated an hepatitis C treatment, 133 (77.8%) had an hepatitis C virus RNA test 12 weeks after
the end of treatment. Of these 133 patients, 95.5% (n = 127) achieved sustained virologic response. Twenty-four weeks after the end
of treatment, 135 patients had an hepatitis C virus RNA test (including 23 patients who did not have an hepatitis C virus RNA test
12 weeks before). Of these 135 patients, 127 (93.4%) achieved sustained virologic response. Only one person was re-infected with
hepatitis C virus due to injection drug use. The remaining 7 patients did not achieve sustained virologic response at week 24 due to
treatment failure. A total of 156 patients had an hepatitis C virus RNA test during the study period, of whom 149 (95.5%) achieved

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M. Gagné, I. Têtu, J.-P. Grégoire et al. International Journal of Nursing Studies Advances 3 (2021) 100029

Table 2
Clinical characteristics of patients at treatment initiation (N = 171).

Clinical characteristics N (%)

Patients
Body mass index (kg/m2 )
<18.5: underweight 4 (2.3%)
18.5 to 24.9: normal weight 55 (32.2%)
25 to 29.9: overweight 58 (33.9%)
>30: obese 32 (18.7%)
Missing data 22 (12.9%)
Had any of the following physical health problems: 115 (67.3%)
Comorbid physical health problem:
Cancer (other than hepatocellular carcinoma) 3 (1.8%)
Hepatocellular carcinoma 2 (1.2%)
Diabetes 26 (15.2%)
Chronic pain 35 (20.5%)
Hepatitis B 9 (5.3%)
Cardiovascular disease 41 (24.0%)
Chronic inflammatory disease 16 (9.4%)
Chronic pulmonary disease 39 (22.8%)
Chronic kidney disease 10 (5.9%)
Thromboembolic disease 2 (1.2%)
Human immunodeficiency virus/acquired immune deficiency syndromea 7 (4.1%)
Had any of the following mental health problems: 135 (79.0%)
Comorbid mental health problem:
Anxiety 52 (30.4%)
Alcoholism 40 (23.4%)
Bipolarity 6 (3.5%)
Schizophrenia 7 (4.1%)
Substance addiction 99 (57.9%)
Adjustment disorder 2 (1.2%)
Attention deficit disorder 20 (11.7%)
Personality trouble 60 (35.1%)
Active major depressive disorder, first episode 2 (1.2%)
Recurrent major depressive disorder 52 (30.4%)
Other mental health problem 4 (2.3%)
Alanine aminotransferase (U/L)
≥0 and ≤50b 67 (39.2%)
>50 85 (49.7%)
Missing data 19 (11.1%)
Total bilirubin (mmol/L)
≥0 et ≤21b 121 (70.8%)
>21 8 (4.7%)
Missing data 42 (24.6%)
Creatinine (𝜇ml/L)
<55 13 (7.6%)
≥55 et ≤105b 121 (70.8%)
>105 10 (5.9%)
Missing data 27 (15.8%)
Gamma-glutamyl transpeptidase (U/L)
<50b 55 (32.2%)
≥50 67 (39.2%)
Missing data 49 (28.7%)
Haemoglobin (g/L)
<140 66 (38.6%)
≥140 et ≤180b 91 (53.2%)
Missing data 14 (8.2%)
Platelet count (109 /L)
<150 48 (28.1%)
≥150 et ≤400b 110 (64.3%)
Missing data 13 (7.6%)
Thyroid-stimulating hormone (mUI/L)
<0,25 1 (0.6%)
≥0,25 et ≤5b 123 (71.9%)
>5 5 (2.9%)
Missing data 42 (24.6%)
Hepatitis C virus
Hepatitis C virus genotype
1a 93 (54.4%)
1b 15 (8.8%)
2 13 (7.6%)
3 43 (25.1%)
4, 5, 6 and 1+3 7 (4.1%)
(continued on next page)
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Table 2 (continued)

Clinical characteristics N (%)

Hepatitis C virus infection

Injection drug use 140 (81.9%)
Other mode of transmissionc 31 (18.1%)
Liver fibrosis
Absent, mild or severe fibrosis (F3-F0) 74 (43.3%)
Advanced fibrosis (F4) or cirrhosis 77 (45.0%)
Missing data 20 (11.7%)
a
These seven people who were co-infected with human im-
munodeficiency virus had an undetectable viral load.
b
Normal values.
c
Other modes of transmission include: using intranasal drugs;
recipients of blood transfusions; being born to a mother infected
with hepatitis C virus; unregulated tattooing and piercing in
prisons, etc.

Table 3
Recent illicit drug, alcohol, and tobacco use by patients before treatment initiation
(N = 171).

Substance used in the past 30 days N (%)

Illicit injection drug

None used 134 (78.4%)
Used only one drug 29 (17.0%)
Used ≥2 drugs 8 (4.7%)
Injected:
Amphetamine 1 (0.6%)
Cocaine 25 (14.6%)
Opioid 19 (11.1%)
Another injection drug 1 (0.6%)
Illicit non-injection drug
None used 103 (60.2%)
Used only one drug 45 (26.3%)
Used ≥2 drugs 23 (13.5%)
Used:
Amphetamine 30 (17.5%)
Cocaine or crack 13 (7.6%)
Cannabis 46 (26.9%)
Opioid 5 (2.9%)
Gamma hydroxybutyrate (GHB) drug 1 (0.6%)
Another stimulant 1 (0.6%)
Number of standard alcohol drinks per weeka
0 103 (60.2%)
1 to 7 24 (14.0%)
8 to 14 8 (4.7%)
15 to 21 9 (5.3%)
>21 26 (15.2%)
Drink alcohol, but could not recall how many drinks a week 1 (0.6%)
High-risk drinking 37 (21.6%)
Current tobacco smoker 112 (65.5%)
a
In women, low-risk drinking is defined as no more than 10 standard drinks a week.
In men, low-risk drinking is defined as no more than 3 drinks a day or 15 standard
drinks a week. One standard drink is equivalent to one regular beer (340 ml/12 oz,
5% alcohol), one glass of wine (140 ml/5oz, 12% alcohol), one glass of fortified wine
(85 ml/3oz, 20% alcohol) and one shot of spirits (45 ml/1.5 oz, 40% alcohol).

sustained virologic response (15 patients were deemed not to have achieved sustained virologic response due to missing data for this
outcome in their record). The 149 patients who achieved sustained virologic response correspond to 87.1% of the cohort.

3.8. Characteristics associated with achievement of sustained virologic response

Results of univariate regression analyses of the association between sustained virologic response achievement and each of the
independent variables are presented as Online Supplementary Material 7. In multivariate analyses, patients who had a criminal record
were less likely to achieve sustained virologic response (patients who had a criminal record vs. not: adjusted prevalence ratio 0.87,

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Table 4
Health services use by the 171 patients before, during, and after treatment.

From the first visit at the nurse-led
clinic to treatment initiation
(N = 171)
Health services
N (%)
During the 12-week period
During the course of the hepatitis C following treatment cessation
treatment (N = 158) (N = 136)
N (%) N (%)

Was hospitalized 10 (5.9%) 8 (5.1%) 2 (1.5%)

Visited the emergency 10 (5.9%) 13 (8.2%) 5 (3.8%)
Consulted a nutritionist 5 (2.9%) 2 (1.3%) 0 (0%)
Consulted a pharmacist 77 (45.0%) 2 (1.3%) 0 (0%)
Consulted an outreach worker 87 (50.9%) 73 (46.2%) 51 (38.6%)
Consulted a nurse 171 (100.0%) 158 (100.0%) 131 (99.2%)
Consulted a general practitioner 33 (19.3%) 37 (23.4%) 24 (18.2%)
Consulted an infectious disease 6 (3.5%) 6 (3.8%) 7 (5.3%)
physician
Consulted a gastroenterologist 163 (95.3%) 71 (44.9%) 52 (39.4%)
Consulted another specialist doctor 27 (15.8%) 22 (13.9%) 14 (10.6%)
Received services from a community 68 (39.8%) 67 (39.2%) 53 (39.9%)
organization
Mean number (±standard deviation) N/A N/A 5.8 (± 4.2) 2.9 (± 0.7)
of visits scheduled at the nurse-led
clinic
Mean number (±standard deviation) N/A N/A 6.9 (± 4.9) 4.0 (± 2.4)
of visits scheduled at the nurse-led
clinic that patients attended
Difference between the number of
visits scheduled and the number of
visits that occurred at the nurse-led
clinic
Lower number N/A N/A 29 (18.4%) 14 (10.6%)
Equal number N/A N/A 61 (38.6%) 53 (40.2%)
Higher number N/A N/A 68 (43.0%) 65 (49.2%)

N/A: Not applicable

95% confidence interval 0.79–0.97). Patients who were non-adherent to their hepatitis C treatment were also less likely to achieve
sustained virologic response (non-adherent vs. adherent adjusted prevalence ratio 0.81, 95% confidence interval 0.68–0.98).

4. Discussion

4.1. Key findings

First, this prospective cohort study shows that a high proportion of vulnerable people initiating an hepatitis C treatment at
a community-based nurse-led clinic adhered to their hepatitis C treatment and achieved sustained virologic response. Second, an
hepatitis C treatment length of 48 weeks (vs. 8 or 12 weeks) and recent use of illicit drugs (vs. non-use) were identified as key
independent factors associated with a lower likelihood of adherence in our study population. Third, patients with a criminal record
and those who were non-adherent to the prescribed hepatitis C treatment were less likely to achieve sustained virologic response.

4.2. Explanation of findings

Our results show that more than half of patients initiating an hepatitis C treatment at the nurse-led clinic had a criminal record
and were considered as having substance addictions. When provided with nurse-led care in the community, a high proportion of
these vulnerable people not only engage in their care by attending all their scheduled follow-up visits, but are also adherent to their
treatment and, in turn, achieve sustained virologic response. As such, this study adds to a growing body of evidence from studies
conducted in prison settings suggesting that nurse-led clinic can safely and efficiently coordinate interdisciplinary hepatitis C care
(Perrett, 2011; Tait et al., 2010), as well as improve treatment uptake (Lloyd et al., 2013) and outcomes in people with hepatitis C
(Overton et al., 2019; Papaluca et al., 2019). Our results nevertheless contrast with those of a cluster randomized controlled trial
comparing nurse-initiated vs. physician-initiated hepatitis C therapy in a community setting (Lewis et al., 2016). In this trial, where
nurses’ role was limited to offering immediate antiviral therapy, uptake and adherence remained poor in vulnerable people and were
not different between the two groups (Lewis et al., 2016). By contrast, in the present study, services provided at the nurse-led clinic
were both tailored to the specific needs of the vulnerable populations and highly consistent with strategies developed to improve
satisfaction with care among vulnerable people (Gentil et al., 2020). For instance, patients could attend all their hepatitis C-related
medical appointments in a strategic location, close to where they lived (a key enabler to treatment engagement among vulnerable
people) (Wolstenholme et al., 2020). To avoid transport-related problems, outreach workers picked up patients for their appointments
and drove them to the clinic. Nurses who acted as case managers ensured continuity of care (Gentil et al., 2020) as well as provision

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M. Gagné, I. Têtu, J.-P. Grégoire et al. International Journal of Nursing Studies Advances 3 (2021) 100029

of health and social services that tackled not only the physical and mental illnesses of vulnerable patients, but also their addictions,
as others called for (Luchenski et al., 2018). As such, services provided at the community-based nurse-led clinic may have driven its
apparent success in terms of uptake, adherence, and sustained virologic response.
Our findings suggest that recent illicit drug use (vs. non-use) and hepatitis C treatment duration (48 weeks vs. 8 or 12 weeks)
are key factors associated with a reduced likelihood of treatment adherence. Treatment non-adherence and having a criminal record
were identified as independent factors associated with a lower likelihood of sustained virologic response achievement. These findings
are consistent with those from a previous meta-analysis that showed that recent illicit drug use was associated with non-adherence
(Hajarizadeh et al., 2018). Treatment adherence has also been reported in the past to be the strongest predictor for sustained virologic
response (Vo et al., 2015).

4.3. Future directions

Effective treatments are widely available and concerted efforts to eliminate hepatitis C virus as a public health threat have been
called for by the World Health Organization (World Health Organization, 2016). In this context, our findings are noteworthy, not
only because hepatitis C treatment uptake by vulnerable people is crucial to meet the 2030 hepatitis C virus elimination target
(World Health Organization, 2016), but also because studies have shown that people with substance addictions and those with low
monthly income are less likely to undertake an hepatitis C treatment than others (Nitulescu et al., 2019; Saeed et al., 2020). Our
results suggest that a nurse-led clinic can successfully reach vulnerable populations in a community setting, in order to assist them in
being cured from hepatitis C virus. There is now a need to assess the comparative impact of this nurse-led model of care for vulnerable
people, compared to usual physician-led care, on adherence, sustained virologic response, but also healthcare costs.

4.4. Strengths and limitations

This study has several strengths. All individuals initiating an hepatitis C treatment at the nurse-led clinic during the study period
were included. We were able to comprehensively describe patients, hepatitis C virus infections, and hepatitis C treatments received. We
were also able to study an array of sociodemographic, clinical, and behavioural characteristics potentially associated with treatment
adherence and sustained virologic response achievement.
This study has also limitations. First, data used in this study were originally collected for clinical purpose. Data misclassification
may therefore have occurred (with patients potentially underreporting illicit drug use). Second, patients for whom we found in their
clinical record no information on treatment completion (3.5% of patients) and on sustained virologic response (8.8% of patients)
were considered as non-adherent and as not having achieved virologic response, respectively. Therefore, the proportion of patients
who were found to be adherent to their treatment and the proportion of those who achieved sustained virologic response may have
been underestimated. Finally, in the absence of a comparison group, we were not able to assess the effectiveness of this nurse-led
model of care compared to standard physician-led care. The results of this present study send a potential efficacy signal.

5. Conclusions

Our results suggest that a nurse-led clinic offering outreach services for people infected with hepatitis C virus could fill an important
gap in hepatitis C health services delivered in a community setting. We believe these results can be generalized to patients who initiate
an hepatitis C treatment in clinics that serve vulnerable patient populations similar to those enrolled in this cohort.

Tweetable abstract

High adherence and sustained virologic response in vulnerable people initiating an #Hepc treatment at a community-based
#NPsLead clinic.
Contribution of the paper
What is already known about the topic
Hepatitis C virus triggers a global pandemic. Effective treatments, including direct-acting antivirals, are available and can cure
hepatitis C virus infection in most patients.
In high-income countries, up to 90% of vulnerable people are infected with hepatitis C virus. Adherence to hepatitis C treatment
is suboptimal in this population.
There is a need to develop specific care route to engage the most vulnerable populations in their hepatitis C care. Actual inter-
ventions, however, have been insufficient to effectively prevent the transmission of hepatitis C virus among vulnerable people in a
community setting.
What this paper adds
This prospective cohort study shows that a community-based nurse-led clinic engages vulnerable people in their care. Patients
attend their follow-up visits, adhere to their hepatitis C treatment, and achieve sustained virologic response.
This study identifies hepatitis C treatment length of 48 weeks (vs. 8 or 12 weeks) and recent use of illicit drugs (vs. non-use) as
independent factors associated with a lower likelihood of adherence.
This study suggests that patients with a criminal record and those who are non-adherent to the prescribed hepatitis C treatment
might be less likely to achieve sustained virologic response.

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M. Gagné, I. Têtu, J.-P. Grégoire et al. International Journal of Nursing Studies Advances 3 (2021) 100029

List of abbreviations
RNA: Ribonucleic acid

Authors’ contributions

All authors contributed to the study design. MG wrote the initial draft and [IT, JPG, JM revised it for important intellectual
content. All authors have given final approval of the version to be published and agree to be accountable for all aspects of the work.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to
influence the work reported in this paper.

Acknowledgements

We are grateful to the Clinique de solidarité SABSA Board of Directors who agreed to give us access to patients’ records. We also
thank Annabelle Moisan-De Serres, M.Sc. for assistance in collecting the data, Myrto Mondor, M.Sc. for conducting statistical analyses,
and Dr. Marie-Louise Vachon, M.D. for commenting on a previous version of this manuscript.

Funding sources

This study was made possible through financial support from Merck Canada Inc. to the CHU de Québec-Université Laval Foundation.
This study received additional financial support from the CHU de Québec-Université Laval Foundation. The funding sources had no
role in the design of this study and had no role during its execution, analyses, interpretation of the data, or decision to submit the
results. MG is a postdoctoral fellow supported by the Canadian Institutes of Health Research and the Fonds de recherche du Québec –
Santé.

Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.ijnsa.2021.100029.

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