key: cord-1030755-jnikwiif
authors: Klein, Marina B
title: Simplifying HCV treatment: a pathway to elimination and model for delivering health care to vulnerable populations
date: 2022-01-10
journal: Lancet Gastroenterol Hepatol
DOI: 10.1016/s2468-1253(21)00467-2
sha: a823bdbd56384af29aeb27eab852fdb18a6ea5bf
doc_id: 1030755
cord_uid: jnikwiif

nan

The availability of safe, effective, short-course, all oral direct-acting antivirals (DAAs) has opened the door to the possibility that chronic hepatitis C virus (HCV) infection could one day be eliminated. Consequently, in 2016, WHO set targets for the elimination of HCV as a public health threat by 2030. Achieving elimination without a vaccine requires that more than 80% of the 58 million people currently estimated to be living with chronic HCV worldwide are treated. With less than 10 years to go, the treatment gap remains enormousonly an estimated 21% of the global population with chronic HCV had been diagnosed and, of these, only 62% treated by the end of 2019. 1 Progress towards HCV elimination has been hampered by the many steps required before HCV treatment is initiated and unduly complex follow-up that some health systems and patients cannot complete. In highincome countries, HCV principally affects those who are marginalised or disenfranchised from health services, such as people who inject drugs or those in rural or remote communities and in prisons. Low-income and middle-income countries face additional challenges. While generic drugs have become increasingly accessible and have substantially lowered the cost of treatment, 2 the cost and complexity of pre-treatment assessments such as genotyping, liver fibrosis staging, and ontreatment monitoring place considerable burden on health resources, precluding the expansion of treatment more widely.

Notwithstanding the COVID-19 pandemic, which has slowed progress towards HCV elimination worldwide by disrupting health systems and shifting health priorities, 3 there were already signs that elimination efforts had stalled. Even in countries on track to eliminate HCV, treatment rates had reached a plateau after patients who were already engaged in the health system and waiting to access treatment did so. 4 Reaching those remaining will require simplifying therapeutic models, task shifting to community and primary health-care settings, and reducing the economic burden on health systems and for patients.

As early as 2018, recommendations for simplifying the approach to initial HCV treatment for adults who do not have cirrhosis or HIV were made. 5 Indeed, a variety of real-world studies reporting on decentralised care models have shown such approaches achieve similarly high cure rates as care delivered by specialists across a range of populations and settings. 6, 7 Evidence from randomised trials further supports simplified monitoring. For example, the SMART-C trial compared standard to simplified monitoring using glecaprevirpibrentasvir, dispensing the entire 8-week treatment and requiring only two in-person visits. 8 Sustained virological response (SVR) was 92%, compared with 95% in the standard of care group, although the difference was not non-inferior. However, this trial excluded active injection drug users and people with cirrhosis, only 7% of participants had HIV infection, pretreatment HCV genotyping was required, and the trial was conducted in high-income settings.

In The Lancet Gastroenterology & Hepatology, Sunil Solomon and colleagues 9 report the results of the MINMON (ACTG A5360) trial, which simplifies HCV treatment even further. All participants received the entire 12-week course of sofosbuvir-velpatasvir at entry; no pre-treatment genotyping was required; FIB-4, a simple laboratory-based test, was used to classify cirrhosis; and there were no scheduled visits or laboratory monitoring while on treatment. Two remote contacts were made using the participant's preferred method of electronic communication. Although there was no comparator arm, this trial demonstrated this highly simplified, patient-friendly approach is both feasible and results in high cure rates (SVR 95·0%, 95% CI 92·4-96·7), similar to those those seen in registration trials. The trial had remarkably few dropouts (n=2) or losses to follow-up (n=2) and was conducted in low-income, middle-income, and high-income settings including participants with a wide range of HCV genotypes. The approach was not only highly effective but also safe.

This trial should have important practice-changing implications. Although the benefits for resourceconstrained settings are evident, paradoxically it might be more impactful for high-income settings, which have been particularly slow to adopt decentralised models widely. Given the large proportion of participants enrolled who were co-infected with HIV (42%, 99% of whom were virologically suppressed) and a reasonable proportion (9%) with compensated cirrhosis, the study is generalisable and supports the expansion of simplified treatment to these groups.

Are there patients for whom a simplified approach might not yet be recommended? Although the trial included patients with a history of substance use, there were relatively few active users (14%). The proportion actively using injection drugs was not clear-a group for whom concerns regarding adherence and difficulties with follow-up due to a lack of mobile phones, computers, or fixed addresses are often raised. That said, only three of 20 non-responders were active substance users. This leaves relatively few patients who still require specialty care (eg, those with prior treatment, advanced cirrhosis, after transplantation, pregnancy, and other liver diseases such as hepatitis B). More research is needed to support such approaches for these special populations.

The MINMON trial adds to the growing body of evidence that DAAs can be delivered safely and simply to a wide range of populations without the need for intensive monitoring and follow-up. It is time to reframe modern HCV treatments. Aside from their continued high price tag, 10 these antivirals are more akin to antibiotics, and we should move to adopt simplification more broadly. Dispensing the full treatment course and offering flexible means of communication increases autonomy for patients and allows them to take control of an infection that remains stigmatising, without risking treatment failure. Adopting such simplified treatment can support a greater role for primary care, community-based, and nurse-led strategies, bringing treatment closer to people living with HCV. Not only can such simplified approaches advance HCV elimination efforts, but they could also serve as models for delivering health care that could change the way we manage infectious diseases affecting vulnerable populations.

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Effect of voluntary licences for hepatitis C medicines on access to treatment: a difference-in-differences analysis

Impact of COVID-19 on global HCV elimination efforts

Australia in danger of missing 2030 hepatitis C elimination targets

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