Treatment of HCV in persons who inject drugs: Treatment as prevention

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Abbreviations

DAA

direct‐acting antiviral

HCV

hepatitis C virus

NSP

needle and syringe program

OST

opioid substitution therapy

PWID

people who inject drugs

SVR

sustained virological response

Globally, morbidity and mortality caused by hepatitis C virus (HCV) infection continues to grow, particularly among aging cohorts of people who inject drugs (PWID).1 Ongoing HCV transmission also remains a problem among young and at‐risk PWID.2

Combined opioid substitution therapy (OST) and high‐coverage needle and syringe programs (NSPs) can reduce HCV incidence by up to 80%,3, 4, 5, 6, 7 with data suggesting that OST alone can also reduce HCV transmission by 53% to 61%.8, 9, 10, 11 Mathematical modeling studies suggest that HCV treatment among PWID could lead to substantial reductions in HCV prevalence and reduce transmission,12, 13, 14, 15, 16 particularly when combined with OST and NSPs.13

Given the high risk for HCV transmission among PWID and the fact that cure after direct‐acting antiviral (DAA) therapy eliminates infectiousness, international recommendations have suggested that PWID are a high priority for treatment, given the potential prevention benefits.8, 17, 18, 19 The availability of tolerable, effective all‐oral DAA‐based regimens have overcome the poor tolerability of interferon‐based therapy, providing an important tool to achieve scale‐up of HCV therapy in PWID.

PWID include people who injected at least once in their lifetime and have ceased injecting (“former PWID”) and people with recent injecting (“recent PWID”, with definitions for recent injecting drug use varying from in the last month to the last year). Among the population of people receiving OST, there are both former PWID and recent PWID, with transitioning between these defined populations. Phase 3 clinical trials often include former PWID and people on OST (with no recent drug use) and often exclude recent PWID (including those receiving OST with recent drug use).

Among people receiving OST and no recent illicit drug use, recent post hoc analyses of phase II/III trials of DAA therapy have demonstrated that treatment completion, adherence, and sustained virological response (SVR) is similar to those not receiving OST.20, 21, 22, 23, 24, 25, 26

Data on DAA treatment outcomes among people receiving OST with recent illicit drug use are now available.27 Treatment‐naive individuals with HCV genotype 1/4/6 infection receiving “stable” OST (≥80% adherence to OST appointments in the last 3 months, recent drug use permitted) were treated with elbasvir/grazoprevir for 12 weeks. Overall, 96% completed therapy, more than 96.5% of participants demonstrated more than 95% adherence, and SVR12 was 91%.27 Importantly, drug use at baseline (62% all, 47% noncannabinoids) and during treatment (60% all, 47% noncannabinoids) did not impact SVR.27 These data provide strong support for the efficacy and safety of DAA therapy in people receiving stable OST, including those with recent drug use.

Among people with recent illicit drug use (including those not receiving OST), real‐world data on DAA treatment outcomes is emerging, with responses ranging from 95% to 98%.28, 29 However, these studies do not distinguish between those with and without recent injecting drug use. Further data on HCV treatment among people with recent injecting drug use are needed. However, this should not be a reason for withholding DAA treatment from recent PWID. At a population level, the prevention benefits of HCV treatment will only be achieved through the expansion of DAA treatment to people with recent or ongoing injecting drug use.

Reinfection is often raised as a concern in the treatment of recent PWID. After successful HCV treatment, positive HCV antibodies do not provide protection against re‐exposure, and HCV reinfection can occur in people with ongoing risk behaviors for acquisition. Among people with a history of injecting drug use, the rate of reinfection after interferon‐based therapy is 2 to 3 per 100 person‐years, with higher rates of reinfection observed among people with recent injecting after interferon‐based therapy (6 per 100 person‐years).30 Among people receiving OST (including recent injecting drug users), the rate of reinfection after successful therapy with elbasvir/grazoprevir therapy was 4 per 100 person‐years.31

There are several key points to consider with respect to HCV reinfection. First, there needs to be acknowledgment that HCV reinfection will occur after HCV treatment among recent PWID. If reinfection is not observed, it is probably not a population of recent injectors, and it is unlikely that there will be any treatment as prevention benefit. Second, optimization of OST and high‐coverage NSP will be crucial for HCV reinfection prevention, given that the incidence of HCV reinfection will reflect the incidence of primary HCV infection in the community. Third, it is important that there is rapid scale‐up of HCV DAA therapy among recent PWID. A slow HCV therapy scale‐up will lead to people who are “susceptible” to reinfection, without substantially reducing the viremic population. A rapid HCV therapy scale‐up will lead to an initial increase in the numbers of HCV reinfection, but as the viremic population decreases over time, reinfection will also decrease. Fourth, individual strategies such as treatment of injecting network partners may also be useful in reducing reinfection (e.g., “bring a friend” treatment strategy). Lastly, it is crucial that there is access to retreatment of HCV reinfection without stigma and discrimination.

Broadened access for HCV care among PWID will require several key components. First, it will be essential to improve global access to OST and high‐coverage NSPs. OST and NSPs are crucial interventions for the prevention of HCV infection (and perhaps reinfection); however, less than 50% of countries have adequate OST and/or high‐coverage NSPs. Second, it will be important to scale‐up strategies to enhance HCV testing, linkage to care, treatment, and reinfection prevention. Third, restrictions based on liver disease stage, drug/alcohol use criteria, and provider type that are in place in many settings globally must be removed to enable broad access. In 2016, Australia became one of the first countries to make “access‐for‐all” a public health priority. There are no restrictions based on disease stage, drug/alcohol use, or prescriber type (experienced general practitioners can prescribe DAAs). Similar programs with the potential to achieve HCV elimination goals are required globally, such as those starting to take place in other countries like Egypt, France, Georgia, Iceland, and Portugal.

As we move forward, it will be critical to ensure that “access‐for‐all” includes broadened access to new DAA therapies for PWID so that we can address the substantial burden of HCV infection in this population.