Network-based recruitment of people who inject drugs for hepatitis C testing and linkage to care

Abstract

Although oral direct acting agents (DAA) therapies have the potential to reduce the burden of hepatitis C virus (HCV) infection, treatment uptake remains low, particularly among people who inject drugs (PWID). This study examined the feasibility of an innovative peer-based recruitment strategy to engage PWID in HCV testing and treatment. We interviewed an initial set of HCV antibody positive PWID as “primary indexes” to gather demographic, drug use, health information, and drug network characteristics. Primary indexes were then briefly educated on HCV and its treatment and encouraged to recruit their injection drug “network members” for HCV testing and linkage to care. Eligible network members were enrolled as “secondary indexes” and completed the same index study procedures. In sum, 17 of 36 primary indexes initiated the recruitment of 64 network members who were HCV antibody positive and eligible to become indexes. In multivariable analysis, successful recruitment of at least one network member was positively associated with prior HCV treatment (OR 2.80; CI [1.01, 7.72]), daily or more injection drug use (OR 2.38; CI [1.04, 5.47]), and a higher number of injection drug network members (OR 1.20; CI [1.01, 1.42]). Among the 69 participants with chronic HCV not previously linked to HCV care at enrollment, 91% (n=63) completed a linkage to HCV care appointment, 45% (n=31) scheduled an appointment with an HCV provider, and 20% (n=14) initiated HCV therapy. These findings suggest a potential benefit for peer-driven, network-based interventions focused on HCV treatment experienced PWID as a mechanism to increase HCV linkage to care.

Introduction

Hepatitis C virus (HCV) infection continues to be a major public health challenge in the United States and globally ¹. Chronic HCV infection is associated with significant morbidity and mortality primarily through progression to complications such as cirrhosis, hepatocellular carcinoma (HCC), and end stage liver disease; and it is associated with significant healthcare cost increases ^2–5. In the US, HCV infection has become the leading cause of infectious disease related death ⁶.

People who inject drugs (PWID) are disproportionately impacted by HCV. In contrast to a prevalence of 1.3% in the general population, it is estimated that over 50% of PWID are HCV antibody positive ^7–9. As a result, approximately 40% of the HCV-associated disability-adjusted life-years are attributed to injection drug use (IDU) ¹⁰. In the wake of the national opioid crisis, there was a two fold increase in HCV incidence between 2004 and 2014, largely attributable to IDU ^11–13.

The advent of highly efficacious oral direct-acting antiviral (DAA) regimens of short duration with minimal side effects have transformed HCV treatment and increased therapeutic optimism ^14,15. In fact, the World Health Organization (WHO) has called for the elimination of hepatitis C as a public health challenge by 2030 ¹⁶.

Although PWID remain a core driver of the HCV epidemic, with high HCV prevalence and the potential to sustain ongoing transmission in many parts of the world, HCV treatment uptake has remained low among this group. Recent data from the DAA era suggest that less than 20% of HCV infected PWID in different global settings have ever received HCV treatment ^17–19. To achieve HCV elimination goals, HCV treatment uptake among PWID must increase ²⁰. Patient, provider, and system level barriers have been extensively detailed in previous research and have been linked to low treatment uptake among PWID ^21–25.

Social network approaches have been put forth as a means to address some of the complex barriers to HCV treatment. Social network interventions take advantage of existing social connections to spread information and promote health behavior change ²⁶.Based on social network theory, through group or individual relationships, network members, or peers, provide critical functional social support to one another. Among different levels of support, informational support consists of sharing knowledge, offering suggestions, or giving advice, and has been previously linked to healthcare utilization within populations of PWID ^27–30. Modelling data on HCV transmission and elimination support the importance of considering PWID social network factors in intervention development and its potential impact on reducing overall HCV incidence ³¹. However, to date, there is limited empiric data on the feasibility of network based recruitment of PWID for HCV treatment ³².

This study aimed to evaluate the feasibility of a social network-based approach to recruitment of peers for HCV testing, linkage to care, and subsequent treatment. Specifically, we were interested in examining whether PWID with HCV could serve as informed champions to effectively promote HCV testing and linkage to care within their injection drug networks.

Methods

Study Population.

The study was conducted at an urban infectious disease clinic in Baltimore, Maryland, USA. “Primary indexes” initiated the network-based recruitment strategy utilized in this study. As such, PWID were recruited via referrals from providers and community-based research organizations, as well as from a clinical cohort of HCV positive persons who use drugs (The CHAMPS Study, NCT02402218). Primary indexes were ≥18 years of age, English speaking, HCV antibody positive, and reported injection drug use with another person within 1 year of enrollment. Once enrolled, primary indexes were asked to recruit their injection drug use “network members” for HCV testing and linkage to care. Network members were eligible to become “secondary indexes” if they were ≥18 years of age, English speaking, HCV antibody positive, and had a history of injection drug use.

Assessments.

At the time of informed consent and enrollment, medical records were reviewed for HCV and HIV laboratory test results. Participants without a record of HIV or HCV antibodies were rapid tested (Orasure Oraquick, HCV Rapid Antibody Test, and Rapid HIV-1/2 Antibody Test; Bethlehem, PA). All indexes completed detailed interviewer-administered egocentric network surveys (EgoWeb 2.0, computer software, https://github.com/qualintitative/egoweb), in which participants enumerated all persons in their social network, including injection drug use partners (network members) from the last 5 years. Indexes enumerated drug use network members in response to the question “Who have you injected drugs within the past 5 years? (i.e. they were present and injected drugs on the same occasion when you injected drugs, even if they injected different drugs than you did)”. Indexes reported perceived age, race, gender, duration of relationship, health, and drug use characteristics of each network member. Surveys also collected index sociodemographic characteristics, communication habits, and a comprehensive health history related to HCV, HIV, sexual health, and drug and alcohol use. Lastly, participants provided blood samples for HCV RNA testing and subsequent sequencing. Participants were remunerated $10 for rapid testing, $15 for phlebotomy, and $50 for survey completion.

Brief intervention.

Following the survey, indexes received a brief 2-minute intervention from trained study staff, which included a review of a fact sheet with health information about HCV and its treatment (Supplementary material). They were then encouraged to serve as informed peers and discuss HCV treatment with the specific injection drug network members from the last 5 years, whom they had enumerated in their survey (up to 9). Indexes were given a written list of their drug use network members and the appropriate number of coupons for recruitment. If indexes expressed safety concerns about approaching certain drug network members, these coupons were withheld. Coupons listed study contact information, an expiration date of 3 months after enrollment, and a unique numerical code. Each code linked the network member to their recruiting index. Study staff screened network members who presented with coupons to ensure congruency with the description provided by the index. Network members, matching the description and fulfilling eligibility criteria, became secondary indexes and could then complete study processes and recruit their own reported network members. For each network member who presented for evaluation, indexes were remunerated $10, regardless of the network member’s HCV status.

Linkage to Care.

Based on self-reported data at enrollment, all indexes who were not previously linked into HCV care or cured at the time of enrollment were offered same-day evaluation by a social worker for linkage to care. Social work appointments included an insurance assessment and request for referrals from primary care physicians. If required for insurance purposes, participants were linked to primary care. After the study visit, staff conducted chart reviews to update records with documented linkage to care outcome data. Chart review data was supplemented with phone call follow-ups, which provided self-report data on linkage to care outcomes.

Study outcomes.

The primary study outcome was the successful recruitment of at least one injection drug use network member by an index. The secondary outcome was progression through the HCV care continuum of participants with chronic HCV infection; this was gathered through self-report and medical record review.

Statistical analysis.

Network density was defined as the number of actual ties (number of persons in the index’s social network who know each other) divided by the number of possible ties. The proportion of individuals in an indexes network fulfilling specific criteria (outlined in Table 1) were calculated in the software Enet as summary egocentric network measures ³³. Logistic regression analyses were conducted using generalized estimating equations (GEE) clustered on indexes to assess for factors associated with recruitment of at least one drug using network member. Factors significant at the level of P ≤0.1 in the bivariate analyses were included in the multivariable model. Analyses were conducted in STATA (StataCorp. 2017. Stata Statistical Software: Release 15. College Station, TX: StataCorp LLC) and graphics were created in R Studio using igraph ^34,35

Table 1:

Index- and network-level characteristics among 100 PWID

Characteristic	N (%) N=100
Age, median (IQR)	53.0 (44.0–57.0)
Black race	71 (71%)
Male sex	74 (74%)
High school education or higher	37 (37%)
Homeless	50 (50%)
Monthly income ($), median (IQR)	732.5 (400–1000)
Unemployed	86 (86%)
Live in Baltimore	95 (95%)
Ever been incarcerated	96 (96%)
Lifetime incarceration (months), median (IQR)	48 (12–180)
Anti-HCV +/ RNA +	83 (83%)
Anti-HCV +/ RNA −	17 (17%)
HIV infected	25 (25%)
Previous HCV treatment	33 (33%)
Years injecting, median (IQR)	28 (16–38)
Daily or more injection drug use	47 (47%)
Hazard alcohol use†	67 (67%)
Co-occurring mental health conditions	59 (59%)
Network density, mean (SD)	0.67 (0.28)
Number of network members, mean (SD)	7.6 (3.8)
Number of drug network members, mean (SD)	3.5 (2.4)
Average network age, median (IQR)	50.2 (43.7–55.9)
Average drug network age, median (IQR)	49.5 (39.7–55.0)
Average number of years known drug network members, median (IQR)	13 (4.0–22.0)
Proportion of drug network
Black, mean (SD)	0.7 (0.4)
Male, mean (SD)	0.7 (0.3)
HCV infected, mean (SD)	0.5 (0.4)
HIV infected, mean (SD)	0.1 (0.3)
Sex partners, mean (SD)	0.1 (0.3)
Family, mean (SD)	0.1 (0.2)
Not on good terms with, mean (SD)	0.4 (0.5)

PWID, people who inject drugs; IQR, interquartile range; HCV, hepatitis c virus; Anti-HCV, HCV antibody; RNA +, ribonucleic acid positive; HIV, human immunodeficiency virus; SD, standard deviation

^†Hazard alcohol use defined as a score of 4 ≤ for men and 3 ≤ for women on the AUDIT-C tool

The study protocol was created and conducted in accordance with provisions of the Declaration of Helsinki and Good Clinical Practice guidelines. It was approved by the Johns Hopkins University School of Medicine Institutional Review Board. All study participants provided written informed consent.

Results

Study participants.

Primary Indexes

Between January 2018 and January 2019, 45 primary indexes were recruited through community, clinic, and research referrals, of whom, 36 (80%) were eligible and enrolled in the study. Of the 9 not eligible, 5 were HCV negative on rapid testing, 3 denied injecting with another person in the past year, and one died before completion of the study procedures. Out of the 36 primary indexes enrolled, 17 (47%) successfully recruited at least one network member.

Secondary Indexes

Among the 64 network members who were eligible to become secondary indexes, 62 received coupons to recruit, of whom, 19 (31%) recruited at least one network member. Two indexes did not receive any coupons due to safety concerns about approaching network members.

Primary and Secondary Index network recruitment

In total, 19 primary and secondary indexes recruited one network member, 9 indexes recruited two network members, 6 indexes recruited three network members, 1 index recruited four network members, and 1 index recruited five network members (Figure 1). Among the 75 network members who were recruited, 11 network members were not eligible to become secondary indexes due to screening negative for HCV on rapid testing (n=9), a denial of a history of injection drug use (n=1), and failure to complete the egocentric network survey (n=1) (Figure 2). Within the sample of 100 participants who were enrolled and completed the egocentric network survey, the largest network enrolled indexes to the seventh degree.

Figure 1:

Distribution of network member recruitment among 36 recruiting indexes

Index

Network member

→ Recruited

Figure 2:

Network-based recruitment among 110 PWID

110 PWID consists of 36 primary indexes who did (n=17) or did not (n=19) recruit at least one network member, leading to the total recruitment of 75 network members; of whom, 65 were anti-HCV positive and 9 were anti-HCV negative. One network member did not complete the egocentric interview and was excluded.

Anti-HCV positive primary index

Anti-HCV positive network member

Anti-HCV negative network member

→ Recruited

HCV, hepatitis c virus; Anti-HCV, HCV antibody; PWID, people who inject drugs

Among 100 enrolled PWID, the median age was 53.0 years (interquartile range [IQR] 44.0–57.0; Table 1). The sample was predominantly black (71%) and male (74%). Overall, 37% had a high school education or higher, 86% were unemployed, and 50% were currently experiencing homelessness. Median monthly income was $733 (IQR 400–1000), and the majority of participants (96%) had previously been incarcerated, for a median of 48 (IQR 12–180) months. Approximately half of participants (47%) were injecting at least daily, with a median duration of injection of 28 years (IQR 16–38). HIV coinfection was reported in 25% of participants and co-occurring mental health illness in 59%. At study enrollment, 13% reported a previous lack of awareness of HCV infection, and 33% reported previous or recent initiation of HCV treatment. Overall, 83% (n=83) were chronically infected with HCV, and 17% (n=17) had undetectable HCV viral loads.

Network characteristics.

Among the 100 participants who completed the full egocentric interview, mean overall social network size was 7.6 persons (Standard Deviation [SD] 3.8), and the median overall network age was 50.2 years (IQR 43.7–55.9). The mean size of each injection drug network was 3.5 network members (SD 2.4), with network size ranging from 1 to 9 members. The median age of injection drug network members was similar (49.5 years [IQR 39.7–55.0]) to that of the overall network. By proportion, injection drug networks were primarily black (0.7; SD 0.4) and male (0.7; SD 0.3), representing a high level of network homophily. Indexes reported HCV infection in approximately half of the enumerated injection network members (0.5; SD 0.4). Injection drug networks, on average, included a low proportion of sexual partners (0.1; SD 0.3) and family (0.1; SD 0.2). Overall, mean injection drug network density was 0.67 (SD 0.28), and indexes reported knowing their injection drug use network members for a median of 13 years (IQR 4.0–22.0), suggesting well connected and stable injection drug use networks. Among network members listed by and successfully recruited by indexes, the majority (54%) correctly listed the HCV infection status of the network member. A smaller proportion incorrectly listed (17%) or were unsure (29%) of the network members HCV status in the baseline network inventory.

Primary outcome.

To evaluate factors associated with network member recruitment, we compared the index- and network-level characteristics of indexes who recruited at least one network member (n=36) with indexes who did not recruit any network members (n=64). In bivariate analysis (Table 2), successful network member recruitment was positively associated with ever receiving HCV treatment and having a greater number of injection drug network members. Additionally, participants who injected daily or more frequently were more likely to recruit at least one network member (p=0.11). No additional characteristics that were examined were found to be significantly associated with network member recruitment. In multivariable analysis (Table 2), prior HCV treatment (Odds Ratio [OR] 2.80; 95% Confidence Interval [CI] [1.01, 7.72]) and daily or more injection drug use (OR 2.38; CI [1.04, 5.47]) remained independently associated with network member recruitment. The adjusted model also showed indexes with higher numbers of injection drug network members had higher odds of recruiting at least one network member (OR 1.20; CI [1.01, 1.42]).

Table 2:

Characteristics associated with recruitment of at least one network member among 100 PWID

Characteristic	Univariable OR (95% CI)	Multivariable OR (95% CI)
Age	1.03 (0.99, 1.07)	-
Black race	0.88 (0.41, 1.88)	-
Male sex	1.22 (0.43, 3.50)	1.10 (0.39, 3.12)
HIV infected	1.38 (0.61, 3.10)	-
Previous HCV treatment	2.43 (1.10, 5.37)	2.80 (1.01, 7.72)
Daily or more injection drug use	1.73 (0.88, 3.41)	2.38 (1.04, 5.47)
Network density	0.64 (0.24, 1.66)	-
Number of drug network members	1.24 (1.02, 1.49)	1.20 (1.01, 1.42)
Proportion of drug network
Black	1.38 (0.53, 3.61)	-
Male	1.75 (0.55, 5.55)	-
HCV infected	1.47 (0.54, 3.98)	-
HIV infected	1.75 (0.49, 6.28)	-
Sex partners	1.67 (0.42, 6.70)	-
Family	7.19 (0.47, 109.09)	-

HIV, human immunodeficiency virus; HCV, hepatitis c virus

Secondary outcome.

Overall, 83 of 100 PWID who completed all study procedures had chronic HCV, as 16 were cured before study enrollment, and one experienced spontaneous clearance. An additional 14 were already linked to HCV care, of whom 13 had initiated HCV treatment. Among the 69 PWID who were not linked to HCV care prior to enrollment, 63 (91%) were evaluated by a social worker for linkage to HCV care (dark shading, Figure 3). The other six (9%) refused linkage to care. Of the 69 participants who were not linked to HCV care prior to study enrollment, 45% (n=31) went on to schedule an appointment with an HCV provider, 36% (n=25) completed an appointment, 26% (n=18) were prescribed HCV therapy, 20% (n=14) initiated therapy, and 12% (n=8) had documentation of completion of therapy. We also evaluated the additional 14 (17%) chronically infected PWID who were already linked to HCV care prior to study enrollment (light shading, Figure 3). Overall, in our sample of 83 participants with chronic HCV, 93% (n=77) have been linked to HCV care, 54% (n=45) scheduled an appointment with an HCV provider, 47% (n=39) completed an appointment, 39% (n=32) were prescribed HCV therapy, 34% (n=28) initiated therapy, and 23% (n=19) had documentation of completion of therapy. Of the 21 participants who saw the social worker but did not schedule an appointment with an HCV provider, the primary barrier to HCV care was the insurance requirement of a referral from a primary care provider in order to see an HCV specialist for evaluation (64%). Among those not previously linked who progressed through the care continuum, the mean time from linkage to care to first provider visit was 40 days, and from linkage to care to treatment initiation was 69 days.

Figure 3:

Progress of 83 PWID with chronic HCV through the HCV care continuum

Previously linked

Linked through the study

PWID, people who inject drugs; HCV, hepatitis c virus

Discussion

In this study, approximately half of HCV infected PWID were able to successfully recruit at least one injection drug use network member for HCV testing and linkage to care at an urban infectious disease clinic. While the majority of PWID enrolled through a network member were already aware of their HCV infection, only a minority had been linked to HCV care prior to this study. This is likely a reflection of the complexities of the US health care system related to HCV care engagement, including a limited number of venues for HCV treatment, the requirement for specialist care, and the frequent need for referrals to access specialist care. PWID, such as those enrolled in this study, with low levels of educational attainment, and high rates of unemployment, past incarceration, and co-occurring mental health illness, face significant barriers to health care access. Despite these challenges, this study demonstrates the potential use of social network approaches for recruitment of PWID and emphasizes the importance of innovative strategies to engage more PWID in curative HCV care.

PWID in our study were likely able to link their drug use network members to HCV care by the provision of both social support and peer navigation. Social support from peers has been shown to play a pivotal role in overcoming the complex social barriers faced by PWID ²⁴. In HIV positive populations, higher social support has been linked to improved healthcare utilization ³⁶ and viral suppression ³⁷. Social support measures have also been linked to progress through the stages of the HCV care continuum for PWID, including treatment contemplation, evaluation, and HCV cure ^38–40.

Our significant finding that HCV infected PWID who reported previous HCV treatment were more likely to recruit drug use network members for HCV linkage to care supports the notion that peer-based programs driven by peers who have experienced similar medical treatments can facilitate treatment initiation ⁴¹. HCV infected PWID who have successfully undergone HCV treatment have the potential to serve as champions of HCV linkage to care within their social networks. Treatment experiences shared by these PWID will likely be received with greater credibility and may consequently increase HCV treatment uptake.

As a component of social support, informational support has been linked to improved emergency healthcare utilization ^28,30 and progress through the HCV care continuum among people who use drugs ²⁹. Similarly, having specific network members, such as supportive family members, has been linked to different stages of the HCV care continuum, including HCV treatment initiation and achievement of HCV cure ^39,42,43. Peers enhance health care engagement in different ways, including providing instrumental support, such as appointment scheduling and medication reminders; emotional support in group and individual sessions; financial support; and informational support ^44–46. Discussion of HCV with peers may also reduce HCV associated stigma, a known barrier to care engagement. Our finding of a high level of concordance between reported and actual HCV status of network members, suggests that discussions about HCV are already occurring in PWID networks. It may be beneficial to augment these discussions around HCV with information provided by peers to increase motivation and enhance behavioral skills around HCV care engagement.

In our study, daily or more injection drug use was associated with the recruitment of at least one drug network member. This may be a proxy for frequency of contact; thus, providing opportunities for information sharing. Within the context of HCV elimination efforts, these data suggest the potential for an interventional approach to reach PWID populations at the highest risk of sustaining HCV transmission. These interventions would ideally also include HCV transmission and reinfection prevention training and linkage to substance use disorder care.

Unfortunately, despite high rates of linkage to care, progress through the HCV care continuum was limited by system wide barriers, especially the insurance requirement for a referral from a primary care provider prior to evaluation for HCV treatment. To increase the effectiveness of HCV treatment in marginalized populations such as PWID, it will be critical to simplify HCV care systems to increase uptake ^47,48.

Our study is limited by being a single site study in an urban infectious disease clinic and having a small sample size, which may limit its generalizability. Moreover, we were limited in our ability to evaluate and understand the specific mechanisms that contributed to successful recruitment. However, this is the first study, to our knowledge, utilizing PWID for recruitment of their drug network members for HCV testing and linkage to care in a clinical setting, and is an important proof of concept study. Additionally, indexes were paid $10 for each network member they recruited. Nonetheless, given how nominal the incentive was, we do not believe this would have unduly influenced the decision of the index to recruit their network members for HCV testing and linkage to care. Future studies could more closely examine the role of higher incentives in producing greater yield during network member recruitment.

Overall, our findings suggest a potential benefit for peer-driven, network-based interventions focused on HCV treatment experienced PWID as a mechanism to increase HCV linkage to testing and care among PWID. These PWID were successful in recruiting network members with a brief, 2-minute intervention, which demonstrates potential for implementation in busy clinical settings. These peers would also likely benefit from additional support and training to enhance their ability to provide support to network members who are not currently in HCV care and will require support to progress through the HCV care continuum to cure. Using this approach, peers with high network-level influence can provide social support, including instrumental, informational, and emotional support, which has the potential to overcome some of the complex structural barriers that impede HCV treatment. Larger studies focused on training HCV infected PWID as peer educators/navigators with remuneration paid to these indexes for performing “job functions” of recruiting network members for HCV testing and linkage to care may enhance understanding of how peers with further training may effectively engage PWID at all stages of the HCV care continuum.

Abbreviations:

HCV

Hepatitis C virus

HCC

hepatocellular carcinoma

PWID

people who inject drugs

IDU

injection drug use

DAA

direct-acting antiviral

WHO

World Health Organization

GEE

generalized estimating equations