Shelter-Based Integrated Model Is Effective in Scaling Up Hepatitis C Testing and Treatment in Persons Experiencing Homelessness

Study Population and Study Design

This prospective study was conducted by a multidisciplinary team at four large homeless shelters, two in San Francisco, CA, and two in Minneapolis, MN, from August 1, 2018, to January 30, 2021. These homeless shelters provided supportive services on a daily basis to more than 300 residents in San Francisco and between 170 to 350 residents in Minneapolis. The services provided included shelter, meals, case management, and some level of medical care ranging from basic triage to specialist consultation.

Following informed consent, adults 18 years of age and older seeking shelter services and who were either treatment naive or had not received HCV treatment within the prior 12 weeks were enrolled. In addition, clients experiencing homelessness who were HCV positive and who accessed low-threshold temporary shelters and safety-net liver specialty care were also recruited. Patients with significant medical or psychiatric conditions that prevented consenting or participation in the study were excluded.

Study Procedures

Clients who agreed to HCV testing and who met study eligibility criteria were enrolled, completed a questionnaire, and underwent point of care HCV testing (OraQuick HCV Rapid Antibody Test; OraSure Technology, Bethlehem, PA). Participants who tested negative for HCV antibody were provided information about HCV and its prevention.^{(22, 23)}

Those who tested positive for HCV antibody received a confirmatory HCV RNA test and a standardized 30-minute HCV education. This in-person comprehensive education was delivered using a PowerPoint slide format and was led by a designated nurse, pharmacist, or advanced practice provider. In addition, pre-education and post-education questionnaires^{(24, 25)} were administered, and information on HCV risk factors and HCV awareness was captured. Standard-of-care HCV therapy was offered to all participants with detectable HCV RNA through insurance or patient-assistance programs for HCV by the prescribing provider. Treatment was primarily delivered on-site at the shelters or through coordination with their primary care provider, liver specialty provider, or addiction services. The treatment plan was made at the discretion of the treating provider and in accordance with clinical practice guidelines and insurance restrictions. The medication dispensation, therefore, varied and ranged from directly observed therapy (within addiction services), to weekly or monthly dispensing, to dispensation of all medication supply at the start of therapy. If needed, the study team assisted participants in obtaining insurance and facilitated linkage to primary care services. In San Francisco, a designated HCV registered nurse coordinator managed patients on treatment within the shelters in collaboration with shelter clinic providers, primary care providers, or the San Francisco safety-net liver specialty clinic. In Minneapolis, a Doctor of Pharmacy embedded within shelter clinics managed patients on treatment in collaboration with shelter clinic staff and the Minneapolis safety-net liver specialty clinic. Patients were followed throughout therapy and completed laboratory tests and questionnaires at the end of treatment and at 12 weeks following completion of therapy (SVR). Clinical data, including bloodwork, imaging, medical history, and adherence to medications, were collected from the participants’ medical records. A US $25 incentive was given for HCV testing, and a total of $75 was given following HCV education and completion of HCV therapy, including SVR blood work.

Institutional review board approvals were obtained from the University of California San Francisco and Hennepin Healthcare Human Subjects Research Committee, and all participants provided written consent.

Assessment of Clinical Variables

Active HCV infection was confirmed with a detectable HCV RNA, and response to therapy was evaluated by HCV RNA testing at the end of therapy and at SVR time points. Diagnosis of cirrhosis was made based on abdominal imaging or presence of fibrosis stage 4 (F4) on transient elastography (FibroScan), FibroSURE (Laboratory Corporation of America, Burlington, NC), or FIB-4 index >3.25.⁽²⁶⁾ In addition, fibrosis stage F0-F3 was captured when transient elastography or FibroSURE was available. Cirrhotic decompensation was assessed by presence of ascites, hepatic encephalopathy, or history of variceal hemorrhage. Presence of HCC was captured from clinical records and by liver imaging.

Nonprescription drug use, alcohol consumption, and receipt of substance-use therapy before treatment, at the end of therapy, and SVR time point were assessed by self-report. Alcohol consumption was categorized as (1) none or minimal (<1 drink per month), (2) moderate (more than none or minimal but no more than four drinks/day or 14 drinks/week in men, no more than three drinks/day or seven drinks/week in women), (3) heavy (more than four drinks/day for men, more than three drinks/day for women; or binge drinking [five or more drinks for men, four or more drinks for women, on the same occasion]).⁽²⁷⁾

Statistical Analysis

Descriptive analyses of cohort characteristics were performed to obtain frequency for categorical variables and median (interquartile range [IQR]) or mean (SD) for continuous variables. Patient characteristics between those with and without receipt of therapy and those who achieved SVR at 12 weeks and those who did not achieve SVR were compared using the chi-squared test or the Fisher’s exact test if appropriate for categorical variables and the Mann-Whitney test for continuous variables. Univariate and multivariable modeling was performed with the outcome measures of receipt of therapy and SVR as well as an a priori list of predictors and those predictors with a P < 0.2 on univariate analysis. The multivariable model for the outcome of receipt of therapy was adjusted for age, sex, race, illicit drug or alcohol use within the past year, receipt of HCV education, and severity of liver disease, while the outcome of SVR was adjusted for age, sex, and race. All analyses were performed in Stata 15 statistical software (Stata Corp LP, College Station, TX).

Participants

Participant recruitment strategies included advertisement for availability of HCV testing in the shelters as well as directly approaching 1,199 shelter clients. A total of 772 clients agreed to participate in the study; of these, 766 were deemed eligible. There were no significant differences (P > 0.05) in age, sex, race, or shelter site among those who met or did not meet enrollment eligibility (data not shown).

HCV Screening

During the study, a total of 120 HCV testing sessions were performed (72 in San Francisco and 49 in Minneapolis). Of the 766 participants, 162 (21.1%) tested positive for HCV antibody; of these, 107 (66.0%) had detectable HCV RNA. Patient characteristics overall and by HCV antibody status are summarized in Table 1. Those who were HCV antibody positive were older (median age 55.8 vs. 52.6 years), a higher proportion were men (75.3% vs. 66.2%), and of non-Hispanic White race (39.1% vs. 24.4%) compared to those who were HCV antibody negative. In addition, patients who were HCV positive (vs. HCV antibody negative) were more likely to report having a health care provider (82.6% vs. 73.8%), receipt of prior HCV testing (79.6% vs. 45.2%), history of injection drug use (66.7% vs. 13.0%), history of substance-use therapy (62.4% vs. 37.6%), and illicit drug use within the prior year (84.4% vs. 66.7%). The proportion of participants who reported receipt of prior HCV testing in San Francisco and Minneapolis was 63.4% and 38.6%, respectively; of these, 17.6% and 12.9%, respectively, reported testing positive. Overall, 60.5% of participants who reported having previously tested positive for HCV had active infection with detectable HCV RNA. There was no significant difference in willingness to engage in HCV therapy or in subsequent receipt of HCV therapy between those patients who were viremic who did or did not report prior knowledge of a positive HCV test (90.8% vs. 93.0% and 68.2% vs. 65.9%, respectively).

Chronic HCV Therapy

Of the 107 participants with detectable HCV RNA, 66 (61.7%) initiated standard of care HCV treatment (44 in San Francisco and 22 in Minneapolis). The treatment regimens prescribed were as follows: 43 patients (65.2%) received glecaprevir/pibrentasvir, 18 patients (27.3%) sofosbuvir/velpatasvir, 2 patients (3%) elbasvir/grazoprevir, and 1 (1.5%) patient each of sofosbuvir/ledipasvir, sofosbuvir/ledipasvir+ribavirin, and sofosbuvir/velpatasvir/voxilaprevir. Characteristics of participants with detectable HCV RNA by receipt of HCV therapy are summarized in Table 2. There were no significant differences with respect to sociodemographic status, substance use, history of psychiatric illness, or other medical comorbidities, laboratory, or clinical measures in those who initiated therapy compared to those who did not initiate treatment. However, a significantly higher proportion of patients who did not initiate therapy were from Minneapolis compared to San Francisco (56.1% vs. 43.9%, P = 0.03). In comparing the characteristics of patients with detectable HCV RNA by shelter location, a higher proportion of patients in San Francisco were non-Hispanic White whereas a higher proportion of patients in Minneapolis were Black (P = 0.03). There were no other significant differences in patient characteristics between the two sites (Supporting Table S1).

With respect to severity of liver disease, of the 106 patients with detectable HCV RNA and available data, 19 (17.9%) had cirrhosis, 3 (2.8%) had liver decompensation, and 3 (2.8%) had evidence of HCC; the distribution of these patients was similar in the untreated and treated groups. When evaluating fibrosis stage in participants without cirrhosis by either noninvasive imaging (transient elastography, n = 20) or noninvasive serologic methods (FibroSURE, n = 26), 2 (3.1%) were F0, 15 (23.1%) were F1, 18 (27.7%) were F2, and 11 (16.9%) were F3 (Fig 1A) . Therefore, the overall severity of liver disease by all modalities was 26.2% mild (F0 and F1), 27.7% moderate (F2), and 46.1% advanced fibrosis or cirrhosis (F3 and F4). The distribution of liver disease severity by shelter location is shown in Fig. 1B. Although the proportion of patients with cirrhosis was not statistically different between San Francisco and Minneapolis (P = 1.0), a higher proportion of patients from Minneapolis had F0-F1 and conversely, a higher proportion in San Francisco had F2-F3 severity (P = 0.006). The severity of liver disease did not differ significantly between those who did or did not receive therapy in this study.

Chronic HCV Treatment Outcomes

Of the 66 patients who were initiated on HCV therapy, 54 patients (81.8%) achieved SVR, 8 (12.1%) did not achieve SVR, and the SVR status was unknown in 4 patients (6.1%) (Fig. 2). The median time to initiation of therapy was 56 (IQR, 32-107) days overall and longer in Minneapolis compared to San Francisco (76 days vs. 43 days, P = 0.04).

At the start of HCV therapy, 10 patients had a history of prior HCV treatment (3 with pegylated interferon [PEG-IFN]/ribavirin, 4 with DAA, and 3 with unknown prior treatment regimen). Of those with prior PEG-IFN/ribavirin therapy, 1 patient was treated with sofosbuvir/velpatasvir and achieved SVR and 2 were treated with glecaprevir/pibrentasvir, of whom 1 achieved SVR and 1 did not. Of the 4 with prior DAA therapy, 3 had received sofosbuvir/ledipasvir; 1 of these patients was treated with sofosbuvir/velpatasvir and did not achieve SVR, and 2 were treated with glecaprevir/pibrentasvir or elbasvir/grazoprevir and both achieved SVR. One patient was previously treated with glecaprevir/pibrentasvir and treated with sofosbuvir/velpatasvir in the study and achieved SVR. Among those with unknown prior treatment regimen, 2 achieved SVR and 1 patient had an unknown SVR status.

There were no significant differences in rate of SVR among those with known SVR status by treatment site (82.5% in San Francisco, 95.5% in Minneapolis; P = 0.2). However, on intention to treat (ITT) analysis that included all patients, a higher proportion of patients in Minneapolis achieved SVR compared to San Francisco (95.5% vs. 75.0%, P = 0.049). Of the 8 patients who did not achieve SVR, 7 were treatment nonresponders and 1 achieved response at the end of therapy but experienced virologic relapse after discontinuation of therapy. Four patients (1 with relapse and 3 with nonresponse) were retreated for HCV with sofosbuvir/velpatasvir/voxilaprevir; 2 of these patients subsequently achieved SVR, SVR status was unknown in 1 patient, and another patient was deemed noncompliant to retreatment.

Factors Associated With Receipt of Therapy

Univariate and multivariate models of factors associated with receipt of therapy are shown in Table 3. On univariate analysis, shelter location was associated with receipt of therapy. On multivariate analysis, having been enrolled in a shelter in Minneapolis compared to San Francisco was negatively associated with receipt of therapy (odds ratio [OR], 0.3; 95% confidence interval [CI], 0.1-0.7; P = 0.01), while having identified a health care provider was positively associated with receipt of therapy (OR, 4.1; 95% CI, 1.2-14.1; P = 0.02). These associations were independent of age, sex, race, illicit drug or alcohol use within the past year, receipt of HCV education, and severity of liver disease.

Factors Associated with SVR

Characteristics of patients by known SVR status are summarized in Table 4. The median duration of treatment was similar in the SVR and no SVR groups at 58.5 and 58 days (P = 0.1), respectively. In addition, there were no statistically significant differences in patient sociodemographic, clinical, and laboratory characteristics or length of stay at shelter between the SVR and no SVR groups, except those with SVR had significantly lower HCV RNA at treatment initiation (median log₁₀, 6.1 vs. 6.8; P =  0.01) and a higher proportion were adherent to HCV medication by provider report (56.7% vs. 12.5%, P = 0.03). There were no differences in HCV genotype among those who did or did not achieve SVR. Importantly, all 5 patients with genotype 3 achieved SVR. Moreover, 9 of 11 patients with cirrhosis, including both patients with decompensation, had SVR.

On ITT analysis, the only independent predictor of achieving SVR when controlling for age, sex, and race was adherence to HCV medication (OR, 14.5; P = 0.01). Although a higher viral load was associated with lower odds of achieving SVR (median log₁₀ OR, 0.4; 95% CI, 0.2-1.2; P = 0.09), this did not reach statistical significance.