Curative treatments for chronic hepatitis C virus (HCV) infections have existed since 2014. However, even with the availability of a cure, there is still an ongoing HCV crisis within the United States. Between 2015 and 2019, HCV infections in the country increased by 70%. In 2020 alone, HCV contributed to over 14,800 deaths in the United States.

In the face of a growing need for new and innovative treatments, developments in the creation and implementation of long-acting HCV treatment will simplify treatment regimens — allowing people with HCV infections to be tested and cured in a single visit. The emergence of long-acting HCV treatments may address some of the significant barriers that have barred people living with HCV from accessing curative treatment and will be a major step towards HCV eradication.

The Barriers to Current HCV Treatments

Currently, HCV is most commonly treated with direct acting antiviral (DAA) oral medication regimens. DAA treatment regimens can lead to viral eradication of HCV in more than 98% of patients living with chronic HCV infections. The most common and widely available DAA treatment includes a daily oral medication regimen over the course of 8-12 weeks. In addition to a daily oral medication, current DAA treatment regimens require regular monitoring, liver scans, and frequent blood work.

Although safe and effective treatments for HCV are widely available, existing systemic barriers hinder HCV eradication efforts and limit access to DAA oral medication regimens among the most vulnerable populations. The cost of DAA treatment regimens, insurance coverage issues, sobriety requirements, insufficient support systems, and issues with medication adherence prevent people with HCV from accessing curative treatment. Further, the regular monitoring, scans, and blood work requirements of the current treatment models are needlessly cumbersome and hinder marginalized people’s ability to access and adhere to treatment. There is a call for simplifying the current DAA treatment regimens in order to make HCV treatment more accessible to those most impacted. These barriers disproportionately impact vulnerable populations who are already marginalized from health services, including people who inject drugs, people who are incarcerated, and people suffering from insecure housing and homelessness.

People who inject drugs (PWID) disproportionately suffer from chronic HCV infections, as sharing and reusing consumption equipment drastically increases the risk of infection. In addition to high infection rates, people who inject drugs are less likely to access and adhere to HCV treatment. There are multiple barriers that hinder the ability of people who inject drugs from accessing HCV treatment, including lack of access to harm reduction services, restrictive drug laws, poor linkage to care, prior authorization for treatment coverage, and sobriety requirements for accessing DAA therapy.

People who are incarcerated also face disproportionately high rates of HCV infections, due to riskier behaviors that are more common within prisons and jails. These behaviors include injection drug use, tattooing, unprotected sex, and lack of access to harm reduction services and interventions, including clean syringes and other safe use supplies. In addition to the higher risk of infection while incarcerated, people who are incarcerated are less likely to be able to access HCV treatment. Although treatment for HCV is available in 90% of prisons, treatment is often severely restricted and available only to the most serious cases in correctional facilities due to the cost of DAA therapy and the lack of available trained staff to administer treatments.

Additionally, people who are unhoused are more likely to suffer from HCV infections compared to the general population. People experiencing homelessness face significant and multi-faceted barriers that hinder their ability to access and complete HCV treatment regimens. People who are unhoused are significantly undertreated for HCV, due to unstable residence, competing priorities, lack of reliable transportation, and lack of insurance coverage. 

Keeping up with treatment programs and medication regimens is commonly very difficult for patients who have substance use disorder, are experiencing homelessness and unstable housing, have limited access to reliable transportation, and face other stigmatizing issues. In particular, people who use drugs, people who are unhoused, and people who are incarcerated often struggle with medication adherence. Under the current model of HCV treatment, medication non-adherence is a significant barrier preventing the eradication of HCV among these vulnerable communities.

The Potential of Long-Acting Treatments

At present, DAA treatment regimens require a person to adhere to daily medication regimen that lasts, at a minimum, 8-12 weeks. This current model is unduly burdensome and often makes it impossible for the most vulnerable communities to access HCV treatment. The development of long-acting DAA treatment that do not require long oral medication regimens and one-shot HCV treatments could address both these barriers to treatment and major gaps in HCV eradication among vulnerable populations.

Long-acting parenteral formulations of HCV treatments could diagnose and treat people living with HCV in a single encounter through either injectables or implants. Long-acting DAAs mechanisms currently being developed will also minimize the number of visits to a physician needed for treatment and eliminate the need for weeks-long medication regimens. In addition, they may even allow for patients to be tested and cured of HCV within a single visit.

Investigators are currently working on examining the safety and efficacy of a single subcutaneous injection of RG-101, and the safety, tolerability, and pharmacokinetics of GSK2878175 as a long-acting injectable. Both RG-101 and GSK2878175 have been utilized within HCV oral treatment regimens with success. The investigations of the efficacy and safety of both formulations as injections instead of oral formulations can lead to a possible effective cure for HCV. If approved for human use, these long-acting injectable versions of DAA treatment for HCV would result in single-visit cures for chronic HCV infections.

Additionally, long-acting DAA devices are also currently in development. One notable example is a retrievable coil-shaped long-acting DAA system that would encapsulate and release gram levels of drugs while residing within a patient’s stomach. In fact, this device recently was successfully tested on swine, and researchers found that this drug delivery system can safely and effectively provide at least a month-long dose of DAA for HCV infections. The success of the trial on swine supports the likelihood of the device being safe and effective for human patients.


Not all barriers to HCV treatment for people within vulnerable populations are due to the restrictive and burdensome nature of the current oral medication regimen. Medical mistrust, prohibitive costs, lack of insurance coverage, and discrimination are still prevalent regardless the type of treatment being offered. However, for those who left behind by the current HCV treatment model, these potential long-acting treatments and single-visit cures could address those gaps.

By removing the requirements for medication adherence over significant periods and for continuous physician check-ins and monitoring, people who are most at-risk for chronic HCV infections and who are effectively barred from treatment can more easily access curative treatments that could save their lives. The prospects of long-acting DAA treatment models and single-visit cures for HCV may revolutionize how people within marginalized and vulnerable communities can access HCV treatment — pushing us closer to achieving HCV eradication in the country.