Cover Story

Treating People Who Inject Drugs: How to Reach a Difficult-to-Engage Population

As a population, people who inject drugs have the highest prevalence and incidence of hepatitis C infection. Despite this, people who inject drugs have historically had difficulty accessing treatment, either due to socioeconomic and stigma-related barriers or due to treatment restrictions for people with ongoing drug and/or alcohol use.

Data collected over the last few years have shown that people who inject drugs (PWIDs), recent or otherwise, have rates of adherence and sustained virologic response to interferon-free direct-acting antivirals comparable with the general population.

Jason Grebely

“We’ve made a lot of headway in terms of treatment for people who inject drugs and the evidence has been building that therapy is safe and effective in this population,” Jason Grebely, PhD, from the Kirby Institute, University of New South Wales, Sydney, told HCV Next. “Addressing the low levels of screened and diagnosed is going to be one of the major barriers to HCV elimination going forward.”

Hence, innovative screening techniques and linkage to care will be crucial in a population that includes many young individuals who may be unaware they have HCV or the burden it presents, individuals with economic and housing hardships, and a history of stigma that may prevent a patient from seeking medical attention.

Additionally, to achieve global elimination of HCV, HCV treatment may play a role in HCV prevention given the potential to reduce onward transmission. Increased awareness of HCV and the available treatments among PWIDs will be critical.

“Increasing screening is important, but we need to link that screening to care,” Andrew H. Talal, MD, MPH, from the University at Buffalo, New York, told HCV Next. “It’s going to be important to, one, develop care in places where it generally has not been, such as opioid substitution therapy, but there is also no reason it has to be limited to methadone or buprenorphine programs — it could be any program where substance users gather.”

Point-of-care Assays, Testing

Standard HCV testing requires detection of anti-HCV antibodies followed by confirmatory HCV RNA testing. Studies have shown, however, that a significant proportion of people who were positive for anti-HCV antibodies did not follow-up for HCV RNA testing. Reasons for drop-off included the number of separate visits required and a lack of knowledge from either the health care provider or patient who may not realize HCV RNA testing is necessary to confirm active infection.

“In terms of new technology for testing, there are a couple of things that are very exciting,” Grebely said. “First is the potential of using dried blood spot testing as a way to enhance HCV RNA testing in people who inject drugs. There’s data that suggests it enhances testing and linkage to care; avoids the need for phlebotomy; you’re able to do reflex testing; it’s easy to transport and store; you can use it for other purposes such as HIV infection; and the exciting thing is you can have collection by peers or community workers.”

In addition to dried blood spot testing, Grebely noted the availability of several finger-stick, point-of-care tests for HCV RNA detection. In a recent study, Grebely and colleagues found that the Xpert HCV Viral Load test (Cepheid Inc.) had a sensitivity of 100% and specificity of 99.1% to detect HCV RNA with plasma collected by venepuncture, and a sensitivity of 95.5% and specificity of 98.1% to detect HCV RNA with finger-stick capillary whole blood samples. In eight patients who underwent HCV therapy, the sensitivity and specificity of the assay to detect HCV RNA were both 100%.

While the initial up-front costs for assay-reading instruments and costs per assay are likely to be more expensive than anti-HCV testing and, thus, less relevant in low-prevalence settings, this point-of-care approach may be particularly suitable for screening high-prevalence populations such as PWIDs or those in remote/regional settings.

Andrew H. Talal

Telemedicine

Telemedicine programs that use telecommunication technology to provide health care and monitoring from a distance could provide a much-needed avenue to reach PWIDs who may have difficulty attending regular in-clinic or in-hospital appointments, or feel uncomfortable in such settings.

“We found that patients not only liked telemedicine, but over time began to prefer the convenience of it,” Talal said. “They identified it as ‘one-stop-shopping.’ They did not have any concerns with privacy or confidentiality and reported they would refer others to the program.”

The potential benefits of telemedicine for difficult-to-engage patient populations, such as injection drug users, includes access to provider care for those who reside in medically-isolated locations and for those whose lifestyle would adapt better to remote-access provider care. Additionally, telemedicine can be conducted inexpensively with a camera and computer, and health care providers can use the telecommunication application Zoom, which includes a HIPAA-compliant modality.

“Some of the advocacy groups that are working on advocacy for HCV may ultimately want to join with some of the groups advocating for telemedicine, because both will be increasingly important for this patient population,” Talal said.

However, certain regulatory concerns remain regarding implementation of the telemedicine treatment model, including reimbursement complications, variations in state-mandated license requirements and certification for out-of-state physicians consulting across state boundaries, and ensuring quality and security of telemedicine-based care.

Currently, Talal and colleagues are recruiting patients with HCV from opiate substitution treatment programs for a trial comparing the efficacy and patient-centered delivery of HCV care through telemedicine vs. referral to an offsite liver or infectious disease specialist. The study will also evaluate patient satisfaction with telemedicine and compare treatment initiation, adherence and completion between the two groups.

Remaining Stigma

One of the largest hurdles to overcome in reaching people who inject drugs and engaging them in care is the stigma surrounding illicit drug use and the anxiety these individuals may feel regarding the health care system.

“Physicians and health care providers need to understand that many people who inject drugs have considerable stigma and discrimination from past encounters with the health system. They often have barriers when trying to access services because of limited hours of service, long wait times, shortage of health care practitioners, and oftentimes there’s a lack of coverage for services,” Grebely said. “Because of this stigma and discrimination with HCV, there’s also sometimes an inherent fear of letting down their providers. If people miss an appointment, or forget to get a blood test, they sometimes feel embarrassed that they’ve done those things and don’t present at clinic.”

Grebely added that some PWIDs who may have previously attempted treatment with interferon-based regimens and had to cease treatment due to adverse events may not be aware of the safety and efficacy of newly available direct-acting antivirals. Peer-based support and education through peers, Grebely said, could be an important avenue for spreading the word about new, safer treatments.

“It’s all about building up trust and providing a supportive environment where people want to come to the service and seek care,” Grebely said. “It’s quite important to be trying to go to people where they’re accessing service and not expect them to make their way up to the tertiary health clinic, because it’s also very important to remember that hepatitis C is not the most important priority in people’s lives at that time; they may have many other comorbidities, sometimes mental health disorders. [With] everything that’s going on in the United States with respect to the opioid epidemic, it can be challenging to engage patients who inject drugs in treatment. I think the key thing is, when there’s a supportive environment and these patients are treated with respect, they tend to engage in care, especially with DAA therapy.”

Reinfection, Harm Reduction

Health care providers were previously hesitant to treat HCV in people who inject drugs due to concerns about reinfection and, therefore, treatment would be considered unsuccessful. However, growing evidence shows that HCV reinfection rates among injection drug users are significantly low and one study revealed that most opioid users altered their substance-use behaviors after HCV diagnosis.

“We have to acknowledge that reinfection is going to occur,” Grebely said. “In fact, if there are no cases of reinfection, you’re probably not dealing with the current injecting population — the reinfection rate is going to mirror the rate of primary infection in this population. What we need to focus on is optimizing harm reduction with needle and syringe exchange programs and opioid substitution therapy.”

In the U.S., there are approximately 200 needle and syringe programs; however, many harm reduction programs including syringe exchange programs and opioid substitution programs remain underfunded. Additionally, U.S. government officials have yet to approve safe injection sites or facilities, though the support is growing.

“Some patients are on buprenorphine and may be more stabilized, may have a family and jobs. Other patients are in methadone programs and attend those programs more regularly. Other active substance users may not be in any treatment at all, and others still may be in detoxification,” Talal said. “We need to look at the different heterogeneous subpopulations of substance users in order to be able to identify those that would be most appropriate for certain interventions.”

Studies have demonstrated that needle/syringe exchange programs and opioid substitution therapy are effective interventions to prevent HCV infection and present an opportunity for education and awareness campaigns. According to Grebely, scaling up DAA therapy quickly will have a greater prevention impact. If you slowly treat people, it creates individuals susceptible for reinfection without considerably reducing the amount of circulating virus, he said.

“If you scale up rapidly,” Grebely said, “you reduce the prevalent pool of infection. So, initially, you’ll get a rise of reinfection, but as time goes on and you reduce the amount of virus that’s circulating, you’ll have lower and lower numbers of reinfection.”

Focus for the Future

To achieve the goal of universal HCV elimination, physicians and health care providers need to employ innovative strategies and initiatives to engage PWIDs into HCV therapy. These efforts could include behavioral intervention, such as case management, peer navigation and education programs; increased harm-reduction techniques and programs; and expansion of treatment availability venues, such as substance use treatment facilities, correctional facilities and psychiatric institutions.

Collaboration between advocacy groups and non-profit organizations with standard care facilities could also broaden awareness and bring focus to this difficult-to-engage population with a high prevalence of HCV transmission.

“The opioid epidemic in the United States has led to an increased recognition and realization that HCV is not a finished issue,” Talal said. “Additionally, not all drug users and people who inject drugs are the same and I think we’re beginning to realize that and what those differences are.

“There’s a theory called syndemics, which basically describes substance use as just one manifestation of an entire entity of issues. One cannot think about substance use in a vacuum, but instead think about the societal and environmental factors that shape substance users’ lives,” Talal continued. “Outside the patients who are the easiest to treat and the ones who come for their appointments, we’re going to need to do more and more to engage these other populations.” – by Talitha Bennett

Disclosures: Grebely reports financial connections with AbbVie, Bristol-Myers Squibb, Cepheid, Gilead Sciences and Merck MSD. Talal reports financial connections with Abbott, AbbVie, Chronic Liver Disease Foundation, Conatus, Gilead, Intercept, Merck and Tobira.

As a population, people who inject drugs have the highest prevalence and incidence of hepatitis C infection. Despite this, people who inject drugs have historically had difficulty accessing treatment, either due to socioeconomic and stigma-related barriers or due to treatment restrictions for people with ongoing drug and/or alcohol use.

Data collected over the last few years have shown that people who inject drugs (PWIDs), recent or otherwise, have rates of adherence and sustained virologic response to interferon-free direct-acting antivirals comparable with the general population.

Jason Grebely

“We’ve made a lot of headway in terms of treatment for people who inject drugs and the evidence has been building that therapy is safe and effective in this population,” Jason Grebely, PhD, from the Kirby Institute, University of New South Wales, Sydney, told HCV Next. “Addressing the low levels of screened and diagnosed is going to be one of the major barriers to HCV elimination going forward.”

Hence, innovative screening techniques and linkage to care will be crucial in a population that includes many young individuals who may be unaware they have HCV or the burden it presents, individuals with economic and housing hardships, and a history of stigma that may prevent a patient from seeking medical attention.

Additionally, to achieve global elimination of HCV, HCV treatment may play a role in HCV prevention given the potential to reduce onward transmission. Increased awareness of HCV and the available treatments among PWIDs will be critical.

“Increasing screening is important, but we need to link that screening to care,” Andrew H. Talal, MD, MPH, from the University at Buffalo, New York, told HCV Next. “It’s going to be important to, one, develop care in places where it generally has not been, such as opioid substitution therapy, but there is also no reason it has to be limited to methadone or buprenorphine programs — it could be any program where substance users gather.”

Point-of-care Assays, Testing

Standard HCV testing requires detection of anti-HCV antibodies followed by confirmatory HCV RNA testing. Studies have shown, however, that a significant proportion of people who were positive for anti-HCV antibodies did not follow-up for HCV RNA testing. Reasons for drop-off included the number of separate visits required and a lack of knowledge from either the health care provider or patient who may not realize HCV RNA testing is necessary to confirm active infection.

“In terms of new technology for testing, there are a couple of things that are very exciting,” Grebely said. “First is the potential of using dried blood spot testing as a way to enhance HCV RNA testing in people who inject drugs. There’s data that suggests it enhances testing and linkage to care; avoids the need for phlebotomy; you’re able to do reflex testing; it’s easy to transport and store; you can use it for other purposes such as HIV infection; and the exciting thing is you can have collection by peers or community workers.”

PAGE BREAK

In addition to dried blood spot testing, Grebely noted the availability of several finger-stick, point-of-care tests for HCV RNA detection. In a recent study, Grebely and colleagues found that the Xpert HCV Viral Load test (Cepheid Inc.) had a sensitivity of 100% and specificity of 99.1% to detect HCV RNA with plasma collected by venepuncture, and a sensitivity of 95.5% and specificity of 98.1% to detect HCV RNA with finger-stick capillary whole blood samples. In eight patients who underwent HCV therapy, the sensitivity and specificity of the assay to detect HCV RNA were both 100%.

While the initial up-front costs for assay-reading instruments and costs per assay are likely to be more expensive than anti-HCV testing and, thus, less relevant in low-prevalence settings, this point-of-care approach may be particularly suitable for screening high-prevalence populations such as PWIDs or those in remote/regional settings.

Andrew H. Talal

Telemedicine

Telemedicine programs that use telecommunication technology to provide health care and monitoring from a distance could provide a much-needed avenue to reach PWIDs who may have difficulty attending regular in-clinic or in-hospital appointments, or feel uncomfortable in such settings.

“We found that patients not only liked telemedicine, but over time began to prefer the convenience of it,” Talal said. “They identified it as ‘one-stop-shopping.’ They did not have any concerns with privacy or confidentiality and reported they would refer others to the program.”

The potential benefits of telemedicine for difficult-to-engage patient populations, such as injection drug users, includes access to provider care for those who reside in medically-isolated locations and for those whose lifestyle would adapt better to remote-access provider care. Additionally, telemedicine can be conducted inexpensively with a camera and computer, and health care providers can use the telecommunication application Zoom, which includes a HIPAA-compliant modality.

“Some of the advocacy groups that are working on advocacy for HCV may ultimately want to join with some of the groups advocating for telemedicine, because both will be increasingly important for this patient population,” Talal said.

However, certain regulatory concerns remain regarding implementation of the telemedicine treatment model, including reimbursement complications, variations in state-mandated license requirements and certification for out-of-state physicians consulting across state boundaries, and ensuring quality and security of telemedicine-based care.

Currently, Talal and colleagues are recruiting patients with HCV from opiate substitution treatment programs for a trial comparing the efficacy and patient-centered delivery of HCV care through telemedicine vs. referral to an offsite liver or infectious disease specialist. The study will also evaluate patient satisfaction with telemedicine and compare treatment initiation, adherence and completion between the two groups.

PAGE BREAK

Remaining Stigma

One of the largest hurdles to overcome in reaching people who inject drugs and engaging them in care is the stigma surrounding illicit drug use and the anxiety these individuals may feel regarding the health care system.

“Physicians and health care providers need to understand that many people who inject drugs have considerable stigma and discrimination from past encounters with the health system. They often have barriers when trying to access services because of limited hours of service, long wait times, shortage of health care practitioners, and oftentimes there’s a lack of coverage for services,” Grebely said. “Because of this stigma and discrimination with HCV, there’s also sometimes an inherent fear of letting down their providers. If people miss an appointment, or forget to get a blood test, they sometimes feel embarrassed that they’ve done those things and don’t present at clinic.”

Grebely added that some PWIDs who may have previously attempted treatment with interferon-based regimens and had to cease treatment due to adverse events may not be aware of the safety and efficacy of newly available direct-acting antivirals. Peer-based support and education through peers, Grebely said, could be an important avenue for spreading the word about new, safer treatments.

“It’s all about building up trust and providing a supportive environment where people want to come to the service and seek care,” Grebely said. “It’s quite important to be trying to go to people where they’re accessing service and not expect them to make their way up to the tertiary health clinic, because it’s also very important to remember that hepatitis C is not the most important priority in people’s lives at that time; they may have many other comorbidities, sometimes mental health disorders. [With] everything that’s going on in the United States with respect to the opioid epidemic, it can be challenging to engage patients who inject drugs in treatment. I think the key thing is, when there’s a supportive environment and these patients are treated with respect, they tend to engage in care, especially with DAA therapy.”

Reinfection, Harm Reduction

Health care providers were previously hesitant to treat HCV in people who inject drugs due to concerns about reinfection and, therefore, treatment would be considered unsuccessful. However, growing evidence shows that HCV reinfection rates among injection drug users are significantly low and one study revealed that most opioid users altered their substance-use behaviors after HCV diagnosis.

“We have to acknowledge that reinfection is going to occur,” Grebely said. “In fact, if there are no cases of reinfection, you’re probably not dealing with the current injecting population — the reinfection rate is going to mirror the rate of primary infection in this population. What we need to focus on is optimizing harm reduction with needle and syringe exchange programs and opioid substitution therapy.”

PAGE BREAK

In the U.S., there are approximately 200 needle and syringe programs; however, many harm reduction programs including syringe exchange programs and opioid substitution programs remain underfunded. Additionally, U.S. government officials have yet to approve safe injection sites or facilities, though the support is growing.

“Some patients are on buprenorphine and may be more stabilized, may have a family and jobs. Other patients are in methadone programs and attend those programs more regularly. Other active substance users may not be in any treatment at all, and others still may be in detoxification,” Talal said. “We need to look at the different heterogeneous subpopulations of substance users in order to be able to identify those that would be most appropriate for certain interventions.”

Studies have demonstrated that needle/syringe exchange programs and opioid substitution therapy are effective interventions to prevent HCV infection and present an opportunity for education and awareness campaigns. According to Grebely, scaling up DAA therapy quickly will have a greater prevention impact. If you slowly treat people, it creates individuals susceptible for reinfection without considerably reducing the amount of circulating virus, he said.

“If you scale up rapidly,” Grebely said, “you reduce the prevalent pool of infection. So, initially, you’ll get a rise of reinfection, but as time goes on and you reduce the amount of virus that’s circulating, you’ll have lower and lower numbers of reinfection.”

Focus for the Future

To achieve the goal of universal HCV elimination, physicians and health care providers need to employ innovative strategies and initiatives to engage PWIDs into HCV therapy. These efforts could include behavioral intervention, such as case management, peer navigation and education programs; increased harm-reduction techniques and programs; and expansion of treatment availability venues, such as substance use treatment facilities, correctional facilities and psychiatric institutions.

Collaboration between advocacy groups and non-profit organizations with standard care facilities could also broaden awareness and bring focus to this difficult-to-engage population with a high prevalence of HCV transmission.

“The opioid epidemic in the United States has led to an increased recognition and realization that HCV is not a finished issue,” Talal said. “Additionally, not all drug users and people who inject drugs are the same and I think we’re beginning to realize that and what those differences are.

“There’s a theory called syndemics, which basically describes substance use as just one manifestation of an entire entity of issues. One cannot think about substance use in a vacuum, but instead think about the societal and environmental factors that shape substance users’ lives,” Talal continued. “Outside the patients who are the easiest to treat and the ones who come for their appointments, we’re going to need to do more and more to engage these other populations.” – by Talitha Bennett

PAGE BREAK

Disclosures: Grebely reports financial connections with AbbVie, Bristol-Myers Squibb, Cepheid, Gilead Sciences and Merck MSD. Talal reports financial connections with Abbott, AbbVie, Chronic Liver Disease Foundation, Conatus, Gilead, Intercept, Merck and Tobira.