Patient-centred models of hepatitis C treatment for people who inject drugs: a multicentre, pragmatic randomised trial.

BACKGROUND: To achieve WHO targets for the elimination of hepatitis C virus (HCV) as a public threat, an increased uptake of HCV treatment among people who inject drugs (PWID) is urgently needed. Optimal HCV co-located treatment models for PWID have not yet been identified. We aimed to compare two patient-centred models of HCV care in PWID with active drug use. METHODS: We did a pragmatic randomised controlled trial at eight US cities in eight opioid treatment programmes and 15 community health centres. PWID actively injecting within 90 days of study entry were randomly assigned (1:1) to either patient navigation or modified directly observed therapy (mDOT) using computer-generated variable block sizes of 2-6 stratified by city, clinical settings, and cirrhosis status. The randomisation code was concealed, in a centralised REDCap database platform, from all investigators and research staff except for an authorised data manager at the data coordinating centre. All participants received a fixed-dose combination tablet (sofosbuvir 400 mg plus velpatasvir 100 mg) orally once daily for 12 weeks. The primary outcome was sustained virological response (SVR; determined by chart review between 70 days and 365 days after end of treatment and if unavailable, by study blood draws), and secondary outcomes were treatment initiation, adherence (measured by electronic blister packs), and treatment completion. Analyses were conducted within the modified intention-to-treat (mITT; all who initiated treatment), intention-to-treat (all who were randomised), and per-protocol populations. This trial is registered with ClinicalTrials.gov, NCT02824640. FINDINGS: Between Sept 15, 2016, and Aug 14, 2018, 1891 individuals were screened and 1136 were excluded (213 declined to participate and 923 did not meet the eligibility criteria). We randomly assigned 755 participants to patient navigation (n=379) or mDOT (n=376). In the mITT sample of participants who were randomised and initiated treatment (n=623), 226 (74% [95% CI 69-79]) of 306 participants in the mDOT group and 236 (76% [69-79]) of 317 in the patient navigation group had an SVR, with no significant difference between the groups (adjusted odds ratio [AOR] 0·97 [95% CI 0·66-1·42]; p=0·35). In the ITT sample (n=755), 226 (60% [95% CI 55-65]) of 376 participants in the mDOT group and 236 (62% [57-67]) of 379 in the patient navigation group had an SVR (AOR 0·92 [0·68-1·25]; p=0·61) and in the per-protocol sample (n=501), 226 (91% [87-94]) of 248 participants in the mDOT group and 235 (93% [89-96]) of 253 in the patient navigation group had an SVR (AOR 0·79 [0·41-1·55]; p=0·44). 306 (81%) of 376 participants in the mDOT group and 317 (84%) of 379 participants in the patient navigation group initiated treatment (AOR 0·86 [0·58-1·26]; p=0·44) and, among those, 251 (82%) participants in the mDOT group and 264 (83%) participants in the patient navigation group completed treatment (AOR 0·90 [0·58-1·39]; p=0·63). Mean daily adherence was higher in the mDOT group (78% [95% CI 75-81]) versus the patient navigation group (73% [70-77]), with a difference of 4·7% ([1·9-7·4]; p=0·0010). 421 serious adverse events were reported (217 in the mDOT group and 204 in the patient navigation group), with the most common being hospital admission (176 in the mDOT group vs 161 in the patient navigation group). INTERPRETATION: In this trial of active PWID, both models resulted in high SVR. Although adherence was significantly higher in the mDOT group versus the patient navigation group, there was no significant difference in SVR between the groups. Increases in adherence and treatment completion were associated with an increased likelihood of SVR. These results suggest that active PWID can reach high SVRs in diverse settings with either mDOT or patient navigation support. FUNDING: Patient-Centered Outcomes Research Institute, Gilead Sciences, Quest Diagnostics, Monogram Biosciences, and OraSure Technologies.

Telephone Patient Navigation Increases Follow-Up Hepatitis B Care in the Postpartum Period for Immigrants Living in New York City.

Hepatitis B is a major public health threat which leads to serious liver disease or cancer and disproportionately impacts immigrants. Pregnant people are routinely tested for hepatitis B to prevent perinatal transmission but may themselves not receive appropriate education and referrals. People contacted as part of the local health department's perinatal hepatitis B prevention program were offered culturally appropriate telephone patient navigation services to test if this would improve adherence with postpartum hepatitis B care. Four-hundred and nine people were enrolled in the intervention. Using laboratory-reported surveillance data as the outcome measure, those receiving the intervention were 1.66 times as likely to see a hepatitis B care provider within 6 months of childbirth compared with those who did not. Culturally appropriate patient navigation can improve adherence with recommended hepatitis B care in the postpartum period. Health departments can use similar interventions to address liver health disparities in immigrant populations.

Health Department Efforts to Increase Hepatitis C RNA Testing Among People Appearing Out of Care: Comparison of Outreach Approaches, New York City, 2017.

OBJECTIVES: Hepatitis C virus (HCV) infection is a serious health problem in New York City. Although curative treatments are available, many people are out of care. The New York City Department of Health and Mental Hygiene (DOHMH) used surveillance data and various outreach methods to attempt to link to care people diagnosed with HCV infection from 2010 through 2015. METHODS: We randomly assigned people out of care (ie, no HCV test >6 months after first report) to 4 outreach groups: no outreach (control group); letter only; letter and telephone call; and letter, text message, and telephone call. Three months after outreach ended, we analyzed surveillance data to identify people with a subsequent HCV RNA or genotype test suggesting linkage to care. RESULTS: Of 2626 selected people, 199 (7.6%) had a subsequent HCV test. People in all 3 outreach groups had higher odds of a subsequent test than people in the control group (letter only: adjusted odds ratio [aOR] = 1.81 [95% CI, 1.18-2.91]; letter and telephone: aOR = 3.11 [95% CI, 1.67-5.79]; letter, text, and telephone: aOR = 3.17 [95% CI, 1.48-6.51]). People in the letter and telephone group had higher odds of a subsequent test than people in the letter-only group (aOR = 1.72; 95% CI, 1.04-2.74). Most people in the letter and telephone (136/200, 68.0%) and the letter, text, and telephone (71/99, 71.7%) groups could not be reached, primarily because telephone numbers were incorrect or out of service. CONCLUSION: Reaching out to people soon after first report or prioritizing groups in which more recent contact information can be found might improve outcomes of future outreach.

Check Hep C: A Community-Based Approach to Hepatitis C Diagnosis and Linkage to Care in High-Risk Populations.

CONTEXT: In New York City (NYC), an estimated 146 500 people, or 2.4% of the adult population, have chronic hepatitis C virus (HCV) infection and half may be unaware of their infection. Despite a 2014 state law requiring health care providers to screen for HCV infection in primary care settings, many high-risk HCV-positive persons are not, and a large proportion of those screened do not receive RNA testing to confirm infection, or antiviral therapies. OBJECTIVE: The NYC Department of Health's Check Hep C program was designed to increase hepatitis C diagnosis and improve linkage to care at community-based organizations. DESIGN: Coordinated, evidence-based practices were implemented at 12 sites, including HCV antibody testing, immediate blood draw for RNA testing, and patient navigation to clinical services. RESULTS: From May 2012 through April 2013, a total of 4751 individuals were tested for HCV infection and 880 (19%) were antibody-positive. Of antibody-positive participants, 678 (77%) had an RNA test, and of those, 512 (76%) had current infection. Of all participants, 1901 were born between 1945 and 1965, and of those, 201 (11%) were RNA-positive. Ever having injected drugs was the strongest risk factor for HCV infection (40% vs 3%; adjusted odds ratio [AOR] = 19.1), followed by a history of incarceration (18% vs 4%; AOR = 2.2). Of the participants with current infection, 85% attended at least 1 follow-up hepatitis C medical appointment. Fourteen patients initiated hepatitis C treatment at a Check Hep C site and 6 initiators achieved cure. CONCLUSION: The community-based model successfully identified persons with HCV infection and linked a large proportion to care. The small number of patients initiating hepatitis C treatment in the program identified the need for patient navigation in high-risk populations. Results can be used to inform screening and linkage-to-care strategies and to support the execution of hepatitis C screening recommendations.

High HCV cure rates for people who use drugs treated with direct acting antiviral therapy at an urban primary care clinic.

BACKGROUND: Though direct acting antivirals (DAAs) promise high cure rates, many providers and payers remain concerned about successful treatment for people who use drugs (PWUD), even among those engaged in opioid agonist treatment (OAT). The efficacy of DAAs among PWUD in real-world settings is unclear. METHODS: We conducted a cohort study of patients initiating HCV treatment between January 2014 and August 2015 (n=89) at a primary care clinic in the Bronx, NY. Onsite HCV treatment with DAAs was performed by an HCV specialist, with support from a care coordinator funded by the NYC Department of Health. We identified four categories of drug use and drug treatment: (1) no active drug use/not receiving OAT (defined as non-PWUD); (2) no active drug use/receiving OAT; (3) active drug use/not receiving OAT; and (4) active drug use/receiving OAT. The primary outcome was SVR at 12 weeks post-treatment. RESULTS: Overall SVR rates were 95% (n=41/43) for non-PWUD and 96% (n=44/46) for patients actively using drugs and/or receiving OAT [p=0.95]. There were no differences in SVR rates by drug use or drug treatment category. Compared to non-PWUD, those with no active drug use/receiving OAT had 100% SVR (n=15/15; p=1.0), those actively using drugs/not receiving OAT had 90% SVR (n=9/10; p=0.47), and those actively using drugs/receiving OAT had 95% SVR (20/21; p=1.0). CONCLUSION: Regardless of active drug use or OAT, patients who received DAA therapy at an urban primary care clinic achieved high HCV cure rates. We found no clinical evidence to justify restricting access to HCV treatment for patients actively using drugs and/or receiving OAT.

From Care to Cure: Demonstrating a Model of Clinical Patient Navigation for Hepatitis C Care and Treatment in High-Need Patients.

The NYC Department of Health implemented a patient navigation program, Check Hep C, to address patient and provider barriers to HCV care and potentially lifesaving treatment. Services were delivered at two clinical care sites and two sites that linked patients to off-site care. Working with a multidisciplinary care team, patient navigators provided risk assessment, health education, treatment readiness and medication adherence counseling, and medication coordination. Between March 2014 and January 2015, 388 participants enrolled in Check Hep C, 129 (33%) initiated treatment, and 119 (91% of initiators) had sustained virologic response (SVR). Participants receiving on-site clinical care had higher odds of initiating treatment than those linked to off-site care. Check Hep C successfully supported high-need participants through HCV care and treatment, and SVR rates demonstrate the real-world ability of achieving high cure rates using patient navigation care models.

Barriers to Treatment Among New York City Residents with Chronic Hepatitis C Virus Infection, 2014.

OBJECTIVE: New, highly effective hepatitis C virus (HCV) medications recently changed the landscape of HCV treatment. Access to treatment, however, is limited. The New York City Department of Health and Mental Hygiene conducted an enhanced surveillance project to better understand the reasons patients are not treated for HCV. METHODS: In June 2014, we randomly selected 300 adults who were reported through routine surveillance as having a positive HCV ribonucleic acid test result and who had seen a medical provider since June 2012. We collected information on demographics, treatment, and barriers to treatment from these 300 patients and their providers by telephone, fax, mail, and medical record review. RESULTS: Of 179 providers, 74 (41%) cited co-occurring conditions and 50 (28%) cited patients not keeping follow-up or referral appointments with specialists as common barriers to treatment. Forty providers (22%) reported that they do not prescribe HCV medications and instead refer patients to specialists for treatment. Of 89 patients citing barriers to treatment, 30 (34%) cited co-occurring conditions, 26 (29%) cited concerns about side effects, 21 (24%) indicated not feeling sick, 15 (17%) cited waiting for a better treatment regimen, and 12 (13%) cited medication costs or insurance issues. Only 11 providers and 10 patients denied any barriers to treatment. CONCLUSION: Increasing the number of New York City residents with HCV infection who are treated and cured will require programs to increase provider capacity, change provider behavior in treating patients with substance use and medical conditions, improve patient awareness of new medications, provide patient navigation and care coordination support through treatment, and initiate advocacy and policy work.