CONNECT Study: Intervention Improves HCV Testing, But Not Treatment

Tafireyi Marukutira, PhD, MPH, MBChB

Credit: Burnet Institute

Active follow up with notifying primary care practitioners and enhanced case management may help improve hepatitis C (HCV) RNA testing rates, according to findings from the CONNECT study.

A study of HCV RNA testing and treatment examining standard of care compared to intervention, results of the study indicate, despite an increase in HCV RNA testing and trends towards better engagement, treatment uptake remained unaffected.¹

“People living with hepatitis C must be actively engaged in care, via strategies that ensure health care providers are equipped to discuss treatment with patients, prescribe DAAs, or link patients to care,” wrote investigators.¹

Globally, the World Health Organization (WHO) estimates 58 million people have chronic HCV, with about 1.5 million new infections occurring every year. Although direct acting antivirals (DAAs) can cure more than 95% of people with hepatitis C infection, access to diagnosis and treatment is low. Of the 58 million people living with HCV infection globally in 2019, an estimated 21% (15.2 million) knew their diagnosis and around 9.4 million were treated with DAAs.²

To assess the potential of HCV surveillance data for enhancing linkage to treatment, Tafireyi Marukutira, PhD, MPH, MBChB, senior research officer at the Burnet Institute in Australia, and a team of investigators conducted a 2-arm, non-blinded, cluster randomized, controlled trial comparing active follow-up and enhanced case management to standard of care. Study participants were primary care practitioners who ordered an HCV antibody test leading to a new or repeat notification by the testing laboratory to the Tasmanian Department of Health.¹

Notifications from primary care practitioners based outside Tasmania, correctional services, sexual health, or family planning services, and specialists, trainees, or nurse practitioners were excluded. In total, investigators enrolled 171 primary care practitioners with 226 total associated HCV case notifications.¹

For participants in the standard of care arm, Department of Health surveillance officers mailed a surveillance letter and enhanced surveillance data collection form to the notifying primary care practitioner. In addition to the standard of care, participants in the intervention arm received enhanced case management support by a Department of Health hepatitis specialist depending on HCV RNA status, primary care practitioner need, and familiarity with DAA prescribing.¹

Using consecutive HCV notifications, investigators randomized primary care practitioners 1:1 within 3 weeks of their first notification during the 12 month study period. In total, 86 primary care practitioners were randomized to the standard of care arm and 85 were randomized to the intervention arm. Over the observation period, primary care practitioners in the intervention and standard of care arms had 111 and 115 HCV case notifications associated with them, respectively. After obtaining practitioners’ consent, 102 notifications in the standard of care arm and 103 notifications in the intervention arm were eligible for analysis.¹

The primary outcome of interest was the proportion of patients notified with chronic HCV RNA who commenced treatment within 12 weeks of notification. Secondary outcomes included the proportion of patients diagnosed with HCV with a documented RNA detected or undetected test result and the proportion of patients diagnosed with antibody positive HCV RNA.¹

Study arms were compared using proportions with the patient as the unit of analysis. Investigators used univariable logistic regression modeling to explore factors predicting treatment initiation, including patients’ age, sex, previous HCV treatment experience and potential route of transmission, and primary care practitioners’ experience of HCV care or treatment, and opioid substitution treatment prescribing status.¹

Investigators observed a higher rate of HCV RNA testing in the intervention arm, with 92 (89%) patients getting tested compared to 80 (78%) in the standard of care arm (P = .03). Of these patients, 34 in the intervention group and 33 in the standard of care group had RNA detected and were eligible for primary and secondary outcome analysis (P = .56). Of the 11 patients who did not undergo RNA testing in the intervention arm, 6 (55%) were lost to follow-up and 9 (75%) were referred to a specialist, versus 11 (50%) and 7 (58%) in the standard of care arm.¹

Investigators found an 8-point difference in treatment uptake between intervention and standard of care arms over the 12-week post notification period (41% vs 33%; P = .74) and a 17-point difference between arms to the end of the observation period (65% vs 48%; P = .18). The mean time to DAA initiation was similar between the intervention and standard of care study arms (47 days vs 39 days; P = .23).¹

Among the cohort, 13 patients in the intervention group and 12 patients in the standard of care group were previously treated for HCV and had HCV RNA testing. Among the 13 patients in intervention arm, 3 (23%) had RNA detected, of which 2 were retreated. Among the 12 RNA tested patients in the standard of care arm, 5 (42%) had RNA detected and 3 were retreated.¹

Investigators pointed out specialist referral was the most common reason for not initiating DAA treatment through the participating primary care practitioner. Of 12 patients eligible for treatment in the intervention arm, 5 (25%) were referred to a specialist compared to 10 (45%) in the standard of care arm. In a univariable logistic regression of factors associated with treatment initiation, males were more likely to initiate than females (odds ratio, 3.40; 95% CI, 1.0-11.1; P = .04). Investigators pointed out no other significant covariates were associated with DAA uptake.¹

“In light of the high treatment rates in the intervention arm, active follow-up of notifications may significantly impact treatment uptake in jurisdictions with historically low treatment access,” concluded investigators.¹ “In the Australian or similar contexts, adapting this intervention for underserved areas with currently low treatment uptake, using a longer treatment commencement window, or intervening with patients directly instead of their doctor, remains unanswered research questions about how health departments can optimally support HCV treatment efforts.”

References:

1. Marukutira T, Barter R, Moore KP, et al. Connecting patients notified with hepatitis C to treatment (CONNECT Study): A randomized controlled trial of active case management by a health department to support primary care practitioners [published online ahead of print, 2023 Sep 13]. Int J Drug Policy. 2023;121:104184. doi:10.1016/j.drugpo.2023.104184
2. World Health Organization. Hepatitis C. Newsroom. July 18, 2023. Accessed September 20, 2023. https://www.who.int/news-room/fact-sheets/detail/hepatitis-c