HCV care for PWID: ‘Bringing treatment to them’

Simplifying the hepatitis C virus treatment process is essential to improving care among vulnerable populations, particularly people who inject drugs.

“If you look globally, people who inject drugs (PWID) account for well over 60% of cases of HCV, and when you look at new cases or incident infections, that number is often over 80%, so this population is certainly a major driver of new HCV infection in the United States and in much of the Western world,” Benjamin Eckhardt, MD, MS, assistant professor of medicine at NYU School of Medicine and Bellevue Hospital, told Healio.

Historically, HCV was concentrated around the baby-boom generation, with prevalence data from 2005 showing a spike among those born from 1945 to 1965, according to Eckhardt.

“However, in the setting of the more recent opioid epidemic, that historic peak around the baby boomers is now becoming a more bimodal distribution. There is still a peak in that baby-boomer population, but there is also a definite peak among 18- to 29-year-olds or 18- to 35-year-olds, depending on which study you’re looking at,” Eckhardt said. “All of those are new infections and this is being driven by the worsening opioid epidemic across the United States.”

‘A paradigm shift’

When new direct-acting antiviral medications — now a mainstay of treatment for HCV — became available in 2014, clinicians initially focused on treating baby boomers due to the high prevalence of HCV in this population.

Many of these patients, Eckhardt noted, were already engaged in health care related to aging and comorbid conditions and were perhaps not partaking in the behaviors that originally put them at risk for HCV, such as injecting drugs. However, younger patients, among whom HCV infections are currently spiking, typically do not have the same comorbidities, such as cardiovascular disease, and are generally less engaged in health care. This is especially true for young PWID, Eckhardt noted.

“They oftentimes don’t have a primary care physician or are not regulars in a doctor’s office and have a little bit more of a chaotic lifestyle, potentially related to their ongoing drug use,” Eckhardt said. “Therefore, we felt that the current model of care delivery, which is scheduling a patient for a specific time at a community- or hospital-based clinic and making sure that they come to that visit or come to multiple visits before we start treatment, was not something that was going to be widely effective for this patient population. There really needed to be a paradigm shift.”

To evaluate the potential benefits of a more simplified treatment strategy, Eckhardt and colleagues conducted the Rapid Treatment (ST&RT) study — an open-label, randomized, controlled pilot study at the Lower East Side Harm Reduction Center in New York City.

For the study, young, active PWID underwent HCV RNA testing before being randomly assigned to usual care or rapid treatment. In the usual care arm, participants who were HCV antibody-positive were linked to community-based HCV providers and went through the typical cascade of care before initiation of therapy. In the rapid treatment arm, participants were sent home with a 7-day starter pack of Epclusa (sofosbuvir/velpatasvir, Gilead Sciences) and those confirmed HCV RNA-positive were advised in-person or via telephone 2 to 7 days later to initiate treatment. They also returned at day 7 to receive the remainder of their first month of medication.

“We took this model from the HIV world where it has been demonstrated that getting people on HIV medications as soon as they're diagnosed results in better outcomes, both in terms of getting them engaged in care but also in terms of ongoing transmission of the infection,” Eckhardt said. “If you think about it, people who are recently infected are the ones that are most likely to engage in risky behaviors and are also the most likely to then transmit their infection to other potentially uninfected individuals.”

Results showed that more patients both initiated treatment and achieved sustained virologic response at 12 weeks in the rapid treatment arm than in the usual care arm. Additionally, the researchers were able to treat and cure patients more quickly in the rapid treatment arm, according to Eckhardt.

“The goal of this study was to combine the first three, and ideally the first four, steps of this cascade [of care] into a single visit,” Eckhardt said during a presentation of the data at The Liver Meeting Digital Experience. “Compared with the rapid treatment arm, you can see a significant drop-off in engagement and subsequent treatment initiation and cure rate in the usual care arm, all of which are statistically significant.”

A push for minimal monitoring

Simplifying HCV treatment strategies is only one piece of the puzzle. Many researchers and clinicians are also pushing for minimal monitoring while on-treatment as well, according to Eckhardt.

“These new medications really allow for very minimal pretreatment and on-treatment monitoring of these patient populations,” Eckhardt said. “Several studies similar to ours where all 8 or 12 weeks of medication are given to the participant at a single visit with no on-treatment monitoring have shown high success rates. There are also similar national elimination efforts in countries such as Georgia and Rwanda, where very simplified strategies were implemented and high cure rates were achieved.”

Unfortunately, Eckhardt noted, delivery of these medications is often dictated by insurance companies. Prior authorization, for instance, is necessary in some states. Because DAAs often require an 8- or 12-week treatment regimen, patients usually only receive 4 weeks of medication at a time and must return to receive the remainder of their medication, which is often a barrier for patient populations such as PWID.

“The more you require these individuals to adhere to a schedule, the worse outcomes are going to be in terms of getting to appointments,” Eckhardt said. “Our feeling is if you can get the medications to these people and get as many of those pills — ideally, all of them — in hand, they are going to take the medications. They want to be cured, and to me, the easiest way to do it is to diagnose them, confirm they have HCV and give them the pills that they need to get cured.”

During a session at The Liver Meeting Digital Experience, Sunil S. Solomon, MBBS, PhD, MPH, associate professor of medicine in the infectious diseases department at The Johns Hopkins University School of Medicine, discussed evidence supporting the use of minimal monitoring, including results from the large, multinational MINMON study. The strategy employed in MINMON included no pretreatment genotyping, dispensation of all study medication (sofosbuvir/velpatasvir) to complete the 12-week treatment, no scheduled on-treatment clinic visits or lab requirements and remote contact at weeks 4 and 22. Overall, 95% of patients achieved SVR, with no treatment-related adverse events.

These data, coupled with results from other trials such as SMART-C, which also showed high cure rates with minimal monitoring and an 8-week regimen of Mavyret (glecaprevir/pibrentasvir, AbbVie), demonstrate the benefits of scaling back clinic visits and lab testing during the course of HCV treatment, according to Solomon.

“[Simplified treatment] is possible because these drugs are super safe and super effective, and with the pan-genotypic regimens, there is no strong need for extensive pretreatment lab testing, specifically in people who have never been treated before. Also, young people are unlikely to have advanced fibrosis and cirrhosis or other issues that might make treatment less safe, such as kidney disease,” Eckhardt said.

Reducing barriers to care

Another concept for improving HCV care among PWID is increasing access to treatment, according to experts. This includes co-localizing care in other settings, such as methadone clinics or harm reduction centers.

“If we’re going to talk about HCV elimination, co-location of care at community sites catering to PWID, such as syringe service programs, or off-location treatment is something that needs to be explored more,” Eckhardt said. “There is a huge advantage to treating at these sorts of locations in the sense that people feel comfortable coming here. For example, whether they’re using or not, they’re not going to be stigmatized by the staff. There’s an expectation that people are using drugs and that’s why they’re here, and we’re trying to help them with one sort of comorbid condition that came about because of that.”

Unfortunately, Eckhardt noted, there are missed opportunities in this area.

“There is a huge amount of untreated HCV currently in methadone clinics, and the reason for that is the regulations around what a methadone clinic can provide make it extremely challenging to institute HCV treatment on-site. Despite the fact that they cater to a patient population that is at increased risk for HCV, those patients oftentimes have to be referred off-site for treatment,” Eckhardt said. “There needs to be a reevaluation of pragmatic approaches to treatment and figuring out where these individuals are, where they frequent, where they’re comfortable and bringing treatment to them.”

In addition to embedding HCV treatment programs in places such as methadone clinics, there is a need to reduce additional systematic barriers, such as sobriety restrictions, that prevent PWID from receiving care, according to Stacey B. Trooskin, MD, PhD, MPH, CMO and director of viral hepatitis programs at Philadelphia FIGHT Community Health Centers and faculty member at the Perelman School of Medicine at the University of Pennsylvania.

“Particularly in the United States, there are still payers that are not allowing individuals who have substance use disorder and continue to use drugs to be treated for HCV,” Trooskin said during a session at The Liver Meeting Digital Experience.

Currently, 46% of states have no sobriety restrictions for their Medicaid programs, 28% still require documentation that screening and counseling for substance use has occurred prior to treatment, 2% require 1 month of sobriety and 12% require 3 months of documented sobriety, usually through a urine drug screen and sometimes by provider testimony in order to qualify for treatment, according to Trooskin.

“All told, about 24% of states are still requiring individuals to achieve sobriety before they’ll be treated for HCV, which is counterintuitive and counter to the data showing that we need to be treating individuals aggressively and that people who are actively using drugs are not only at highest risk for acquiring HCV but also at the highest risk for transmitting it,” Trooskin said. “We should not be creating additional barriers for individuals to be treated and requiring them to prove sobriety in order to access lifesaving treatment.”

Looking ahead

There are a number of avenues to explore in terms of improving HCV care among PWID, but contact tracing may warrant attention, according to Eckhardt.

“In HCV, we’ve never really done contact tracing because a lot of the infections happened decades ago. However, as current infection is increasingly concentrated in young PWID, there might be a potential role for contact tracing or contact treatment, which would involve defining a network and treating a network together,” Eckhardt said. “We do this in other communicable diseases such as syphilis and gonorrhea because it’s really important not only to treat the person who is infected but to treat their sexual partners as well because otherwise, you’re just going to have cyclical transmission.”

Eckhardt noted that a similar concept could be implemented in HCV treatment where clinicians are treating people who are still engaging in behaviors that put them at risk for reinfection.

“If we can treat them and their network, even if they slip up and share a syringe or a cooker, if that person no longer has HCV, there is not going to be a transmission event,” Eckhardt said.

Additionally, Eckhardt noted that, moving forward, the sustainability of treatment models should be less of a concern when discussing HCV elimination.

“Often, when people talk about co-locating treatment, there is a focus on creating sustainable treatment models. If we’re trying to eliminate something by nature, we shouldn’t be looking at sustainability; elimination is not sustainable,” Eckhardt said. “We just need to invest in achieving elimination. As fewer and fewer people have HCV, it will probably be slightly more expensive to find, engage and treat them because they’re going to be harder to find and less engaged in typical care. To try and pigeonhole ourselves into focusing on sustainable models is misguided.”

References:

• Dore GJ, et al. J Hepatol. 2019;doi:10.1016/j.jhep.2019.10.010.
• Eckhardt B, et al. Parallel 14: Hepatitis C oral session. Presented at: The Liver Meeting Digital Experience; Nov. 12-15, 2021 (virtual meeting).
• Price J, et al. Hepatitis C SIG. Presented at: The Liver Meeting Digital Experience; Nov. 12-15, 2021 (virtual meeting).