The Best Hope for Eradicating HCV

After decades of trying, the world is still in pursuit of a hepatitis C virus (HCV) vaccine, as identifying a target protein on the surface of the virus has been a major stumbling block. There have been breakthroughs, but another method is seen as the shortest route to beating back this virus, which affects 71 million people worldwide and kills 400,000 each year.

Direct-acting antivirals (DAAs), which arrived in 2011, have a cure rate of 95% or better and are so effective and mild in their side effects that public health experts and others say that a massive HCV treatment program could potentially reduce this virus to a negligible health problem. Some of the DAAs currently on the market include Harvoni (ledipasvir/sofosbuvir), Zepatier (elbasvir/grazoprevir) and Epclusa (sofosbuvir/velpatasvir).

Earlier this year, the Biden administration proposed a five-year program to eradicate hepatitis C. Francis Collins, M.D., Ph.D., former director of the National Institutes of Health, was picked to lead the effort. In 2020, the U.S. Department of Health and Human Services issued a report, the “Viral Hepatitis National Strategic Plan for the United States: A Roadmap to Elimination (2021-2025),” which set out an effort to eliminate hepatitis A, B and C as public health threats. Both plans call for much broader access and use of DAAs for hepatitis C. But their price and the question of who will pay for them loom as obstacles.

High prices

HCV, identified in 1989, is the most common bloodborne infectious disease. Risk factors for infection include male-to-male sexual intercourse, incarceration and intravenous drug use. The Centers for Disease Control and Prevention (CDC) has estimated that there were 66,700 acute infections in 2020, a number that has been steadily increasing for years.

A fairly large proportion — estimated to be 20% to 35% — of people infected with HCV spontaneously clear the infection. HCV infection, if left untreated, can lead to diabetes, several types of liver disease and liver cancer. The costs associated with those diseases are far higher than a single round of treatment with DAA.

Overall, fewer than 1 in 3 people with health insurance get DAA treatment for hepatitis C within a year of diagnosis, according to the CDC. The treatment rate is lowest among patients in state-administered Medicaid plans, with fewer than 1 in 4 Medicaid recipients (23%) being treated within a year of diagnosis, according to the CDC.

Carolyn Wester, M.D., M.P.H., director of the CDC’s Division of Viral Hepatitis, and her colleagues used data from Quest Diagnostics to investigate the “clearance cascade” of hepatitis C — how many people who are infected clear the infection on their own or get treated so they achieve viral clearance, which not only spares the infected person from the consequences of hepatitis infection but reduces the risk of transmission of HCV. The goal of the 2020 report was for 80% viral clearance by 2030. In results they reported in June 2023 in Morbidity and Mortality Weekly Report, Wester and her colleagues found viral clearance of just 34% among those who tested positive for HCV from 2013 to 2022. 

The Netflix model

The Biden administration proposed spending $11 billion on its HCV eradication effort, which the administration argued would more than pay for itself because of the savings realized from not having to treat the consequences of HCV infection. Franics Collins, M.D., Ph.D., former director of the National Institutes of Health, was picked to led the effort.

But the DAAs are priced so that a curative course of two or three months can cost, at wholesale prices, between $23,000 and $94,000. Depending on a person’s healthcare insurance and its cost sharing, those prices can put treatment out of reach for many people. In some cases, payers have thrown up barriers to access to protect their budgets.

To solve these problems, the Biden administration proposed following the example set by Louisiana, which in 2019 negotiated with Gilead Sciences to obtain an unlimited supply of DAAs for a lump sum.

This subscription-like payment model, sometimes referred to as the Netflix model, enabled Louisiana health officials to treat as many patients with HCV as they could identify. The number of prescriptions written soared over 534%, and Louisiana paid no more per year — $58 million — than it did before adopting the payment model.

The subscription-like model was first tried successfully on a statewide level in 2018 by Oklahoma for antipsychotic medications. Washington state attempted a subscription-like program to broaden HCV treatment, but it fell short of expectations. The evidence suggests Louisiana’s
follow-through was more aggressive and thorough than Washington state’s, and the Biden administration’s aspirations for eradicating HCV are predicated on having the kind of success that Louisiana has had.

The two dominant manufacturers of DAAs, Gilead and AbbVie, would have to agree to the subscription-like program on a national scale. Depending on how high the prescription prices are set, the companies might find receiving fixed payments attractive because the incremental cost of manufacturing drugs tends to be low.

Medicaid policies

HCV infections have risen sharply for almost all age groups recently but particularly among people under age 40, according to the CDC.

For individuals ages 20 to 29 years, cases rose from 0.5 per 100,000 in 2006 to just under 3 cases per 100,000 in 2019. For those ages 30 to 39, cases were roughly 3.3 per 100,000 in 2019, up from 0.5 in 2009.

The effectiveness of DAAs has bolstered confidence that an aggressive treatment of infected individuals can be prophylactic for the population as a whole and lead to near elimination of HCV. Such an effort would not have been possible for the prior standard of care, interferon-based therapy, which had a far worse tolerance profile and side effects and is curative in, at most, 70% of patients.

There is no telling how far off a vaccine for HCV is, although researchers say they have identified a complex, shape-shifting protein on the virus that could be a successful target for combating this disease.

In the meantime, hopes are resting on the DAAs, which have proved to be effective in real-world application, not just in the highly controlled circumstances of clinical trials. Even patients with advanced cirrhosis of the liver respond well to treatment with DAAs, and treating patients with comorbidities is considered cost-effective. In addition, patients with substance abuse disorders who are not abstaining can be treated successfully with DAAs.

For years, advocates have accused state Medicaid programs of discriminating against HCV patients by throwing up barriers that while holding costs down, often make it impossible for them to obtain treatment. In 2014, the Center for Health Law and Policy Innovation at Harvard Law School and the National Viral Hepatitis Roundtable began publishing state report cards that intensified the pressure to resolve these bottlenecks.

The campaign has had some success. For example, in 2014, 34 states had requirements that patients had to have evidence of fibrosis before Medicaid would cover DAAs. As of June 2022, just two, South Dakota and Arkansas, did. The number of states with requirements for pretesting and specialist reviews has also decreased. But the center has identified prior authorization as an obstacle to hepatitis C treatment, and 38 states have prior authorization requirements.

A key element of the Biden administration’s plan is to employ simplified, point-of-care testing that would enable patients to begin treatment during the same clinic visit. Other goals include training more medical providers to offer medical treatment, providing copayment assistance and expand screening.

The Biden administration also wants to reinvigorate efforts to develop a vaccine, which is important because patients who are successfully cured with DAAs can still become infected. Advocates say education programs are needed to warn patients about this possibility. Also, a lapse in adherence “can reduce the effectiveness of HCV therapy by approximately 75%. Increasing retention in the HCV care continuum is imperative to close the profound HCV treatment gap,” Austin T. Jones, M.D., of Denver Health Medical Center, and his colleagues wrote in a review article published last year in the Journal of Viral Hepatitis.

Tony Hagen is a medical, business and environmental editor and writer in Florence, New Jersey.