Feature

Targeting MSM with HIV: Treatment as Prevention in the Netherlands

The Dutch government has been taking comprehensive steps to deal with HCV. In November 2015, they ruled to treat all patients with HCV, regardless of age, cirrhosis or fibrosis status, risk profile, injection drug use status or sexual orientation. As part of the national HIV guidelines, all individuals with HIV are screened for hepatitis C. The strategies go hand-in-hand, with one overarching aim: treatment as prevention. The goal is to stop transmission of HCV cold. Because men who have sex with men (MSM) with HIV are at the highest risk for transmitting the disease, they placed particular emphasis on testing and treating that population.

Anne Boerekamps, MD, of Erasmus University Medical Center in Rotterdam, the Netherlands, spoke with HCV Next about the Dutch approach, the relevant data, and other topics associated with screening and treating MSM. Her comments are followed by some of the empirical evidence showing the reasons for and success of these interventions.

Why did you choose MSM with HIV to screen, and not another sub-population of patients with HCV?

In the Netherlands, we screen a lot of patient groups, not only HIV-positive MSM. But we choose to do our research on HIV-positive MSM because they visit the hospital twice a year and the incidence of HCV in this risk group is high. When patients end up in HIV care in the Netherlands, they are screened once for HCV antibodies, and twice a year we look at their liver enzymes. When these levels are elevated or if there is clinical suspicion, we do further testing.

What we saw was that in 2015 about 5% of MSM with HIV were coinfected with HCV. That is why we decided to screen this population of MSM. We generally screen subpopulations of the highest risk groups, including IV drug users and baby boomers.

Was there any opposition to this decision among the medical community?

No. People are not against screening in the medical community or even among the general population. In the Netherlands, we are very aware of the ongoing epidemic. There was no division in the medical community. In fact, once a year, we have a national HCV day. At this meeting, we talk with all parties — GPs, sexual health clinics, medical specialists and of course the patient groups — about how to eliminate the infection from our country. This is maybe the most important aspect, because you need to collaborate to eliminate. We know that it may be impossible, but there is momentum.

What obstacles did you face in implementing this program?

Sexual health is mostly under the umbrella of primary care, for HIV-positive patients also secondary care. HCV care is mostly under the umbrella of secondary care, but screening also takes place in primary care, like GP’s and sexual health clinics. Primary care includes, of course, primary care centers, but also sexual health clinics. Secondary care includes HIV clinics. Every region has its own way of doing things, so some centers screen HIV-negative MSM, but others don’t. However, all clinics are supposed to screen HIV-positive MSM. They are required to screen individuals with risk factors at entry, which is something that everybody does. But they are also supposed to conduct yearly HCV-antibody screening in high risk patients, and this is not always done. This is not because physicians are opposed to this program, it is just because they have many other priorities for their patients, and they don’t always remember to do it.

Anne Boerekamps

Did any physicians express reservations or voice concerns about its implementation?

The thing some members are concerned about is the impact and cost of screening. Recent research shows that if we screen patients four times a year, it can be cost effective (data below). This approach can also lead to less transmission of HCV among MSM with HIV. Some clinicians expressed reservations because of the cost. It’s also unclear which party should cover cost: primary or secondary care. Patients with HIV only come to the HIV clinic twice a year, so there is a question about when we can conduct these two other tests. It can be done at primary care, but this, then, raises the question of who covers it.

How can this program reduce HCV transmissions?

If we wait until patients develop severe liver fibrosis, then the incidence rate of hepatitis C infection in the subgroup of MSM with HIV will stay the same. Two basic ways to reduce transmission are to screen for the disease early and treat the disease early. We know that early treatment can slow or stop transmission. This is treatment as prevention, and we think it works. But that’s only treatment. We need to make potentially infected individuals aware that they are at risk.

This is why we recommend partner notification. In our country, you can do this via your sexual health clinic or a special website — https://partnerwaarschuwing.nl/ — which is very easy to use. When patients test positive for HCV, through this online portal, they can send their partners an anonymous text on their phone to get an HCV test. Patients are encouraged to report to their partners that they have HCV. This model is a search-and-destroy technique to reducing transmission.

From consultation, I’ve noticed that most people don’t have a problem with this. Some patients have numbers and names in their agenda. When they find out they are infected, they can trace back to their previous partners.

How can targeting MSM with HIV-HCV coinfection save money and resources?

Before we began this initiative, we also looked at whether implementation of early HCV therapy was cost effective or maybe even cost-saving. Our country has an agreement with pharmaceutical manufacturers that was adequate in lowering cost. The price used to be around 40,000 for 12 weeks, but since the new prices are ‘kept secret,’ the exact costs are unknown at the moment. Most likely, they are lower. A 12 weeks’ course of HCV therapy at the price of 40,000 was cost effective over a period of 40 years, if we lowered the price to 20,000, the HCV therapy was cost saving over a period of 40 years.

Before November 2015, we didn’t treat all patients with HIV/HCV coinfection. After that, we decided to treat all patients regardless of fibrosis state. In the near future, 75% of our cohort will be HCV-free. However, this is still ongoing.

Boerekamps highlighted some key data sets describing the success or potential success of their program.

On reducing new infections:

Rijnders et al. reviewed data from 17 HIV treatment centers from several regions across the Netherlands. Approximately 80% of HIV-positive MSM in the country undergo therapy at these centers. Before DAA therapies became available in 2014, data showed 93 cases of acute HCV in 8,290 person-years of follow-up from these centers (11.2/1,000 PYFU; 95% CI, 9.1-13.7). In 2016, this had decreased to 49 cases in 8,961 person-years of follow-up (5.5/1000 PYFU; 95% CI, 4.1-7.2). The researchers noted that this is a 51% decrease in new infections. This reduction in number of new HCV cases coincided with the uptake of DAA in this patient group.

Impact of unrestricted access to therapy:

Unrestricted access to DAA therapies began in November 2015. The researchers noted that unrestricted access means that all patients can be treated immediately, regardless of fibrosis status. Boerekamps et al. analyzed data for 22,042 individuals with HIV, of whom 1,812 had HCV coinfection. There were 1,420 patients still in care at an HIV clinic. Results indicated that 70% of patients overall were cured or expected to be cured for HCV, while 76% of coinfected patients may reach this outcome.

Model for treating HIV-positive MSM treated before fibrosis:

If all diagnosed patients coinfected with HIV between 2015 and 2030 received DAA therapy, assuming a cure rate of 89% or higher, a model by Hullegie et al. showed a potential reduction in incidence rate from 12 per 1,000 person years to 5 per 1,000 person-years. This compared to a stable incidence rate of 12 per 1,000 person-years for treating patients with F2 or F3 fibrosis. A reduction in prevalence from 5% to 1.4% may also occur, compared with a 6.5% increase for treating at F2 fibrosis or a 7.6% increase for treating at F3 fibrosis. In terms of cost savings, treating these patients will incur a 31 million price tag, which accounts for 27,000 per infection averted. The researchers noted that the cost would be 39 million for deferring to treat at F2 or F3 fibrosis. They added that the economic impact of this strategy depends on the cost of DAA therapies.

On screening patients quarterly:

Lastly, they examined the cost effectiveness of screening four times a year in the general population and the target patient population of HIV coinfected individuals. Currently, this group undergoes ALT measurement twice yearly and antibody testing once a year. At this rate, it is estimated that the incidence rate of new infections would be 5.2 per 1,000 person-years after 10 years. ALT screening every 3 months would reduce this to 4.5 per 1,000 person-years, while PCR screening would reduce this to 4.3 per 1,000. In terms of cost, Popping et al. said that ALT testing costs 2, while PCR testing costs 165. She suggested that implementing these testing programs will be cost-effective, particularly in terms of quality-adjusted life-years gained, if a group of previously infected patients is targeted. – by Rob Volansky

Disclosure: Boerekamps reports no relevant financial disclosures.

The Dutch government has been taking comprehensive steps to deal with HCV. In November 2015, they ruled to treat all patients with HCV, regardless of age, cirrhosis or fibrosis status, risk profile, injection drug use status or sexual orientation. As part of the national HIV guidelines, all individuals with HIV are screened for hepatitis C. The strategies go hand-in-hand, with one overarching aim: treatment as prevention. The goal is to stop transmission of HCV cold. Because men who have sex with men (MSM) with HIV are at the highest risk for transmitting the disease, they placed particular emphasis on testing and treating that population.

Anne Boerekamps, MD, of Erasmus University Medical Center in Rotterdam, the Netherlands, spoke with HCV Next about the Dutch approach, the relevant data, and other topics associated with screening and treating MSM. Her comments are followed by some of the empirical evidence showing the reasons for and success of these interventions.

Why did you choose MSM with HIV to screen, and not another sub-population of patients with HCV?

In the Netherlands, we screen a lot of patient groups, not only HIV-positive MSM. But we choose to do our research on HIV-positive MSM because they visit the hospital twice a year and the incidence of HCV in this risk group is high. When patients end up in HIV care in the Netherlands, they are screened once for HCV antibodies, and twice a year we look at their liver enzymes. When these levels are elevated or if there is clinical suspicion, we do further testing.

What we saw was that in 2015 about 5% of MSM with HIV were coinfected with HCV. That is why we decided to screen this population of MSM. We generally screen subpopulations of the highest risk groups, including IV drug users and baby boomers.

Was there any opposition to this decision among the medical community?

No. People are not against screening in the medical community or even among the general population. In the Netherlands, we are very aware of the ongoing epidemic. There was no division in the medical community. In fact, once a year, we have a national HCV day. At this meeting, we talk with all parties — GPs, sexual health clinics, medical specialists and of course the patient groups — about how to eliminate the infection from our country. This is maybe the most important aspect, because you need to collaborate to eliminate. We know that it may be impossible, but there is momentum.

PAGE BREAK

What obstacles did you face in implementing this program?

Sexual health is mostly under the umbrella of primary care, for HIV-positive patients also secondary care. HCV care is mostly under the umbrella of secondary care, but screening also takes place in primary care, like GP’s and sexual health clinics. Primary care includes, of course, primary care centers, but also sexual health clinics. Secondary care includes HIV clinics. Every region has its own way of doing things, so some centers screen HIV-negative MSM, but others don’t. However, all clinics are supposed to screen HIV-positive MSM. They are required to screen individuals with risk factors at entry, which is something that everybody does. But they are also supposed to conduct yearly HCV-antibody screening in high risk patients, and this is not always done. This is not because physicians are opposed to this program, it is just because they have many other priorities for their patients, and they don’t always remember to do it.

Anne Boerekamps

Did any physicians express reservations or voice concerns about its implementation?

The thing some members are concerned about is the impact and cost of screening. Recent research shows that if we screen patients four times a year, it can be cost effective (data below). This approach can also lead to less transmission of HCV among MSM with HIV. Some clinicians expressed reservations because of the cost. It’s also unclear which party should cover cost: primary or secondary care. Patients with HIV only come to the HIV clinic twice a year, so there is a question about when we can conduct these two other tests. It can be done at primary care, but this, then, raises the question of who covers it.

How can this program reduce HCV transmissions?

If we wait until patients develop severe liver fibrosis, then the incidence rate of hepatitis C infection in the subgroup of MSM with HIV will stay the same. Two basic ways to reduce transmission are to screen for the disease early and treat the disease early. We know that early treatment can slow or stop transmission. This is treatment as prevention, and we think it works. But that’s only treatment. We need to make potentially infected individuals aware that they are at risk.

This is why we recommend partner notification. In our country, you can do this via your sexual health clinic or a special website — https://partnerwaarschuwing.nl/ — which is very easy to use. When patients test positive for HCV, through this online portal, they can send their partners an anonymous text on their phone to get an HCV test. Patients are encouraged to report to their partners that they have HCV. This model is a search-and-destroy technique to reducing transmission.

PAGE BREAK

From consultation, I’ve noticed that most people don’t have a problem with this. Some patients have numbers and names in their agenda. When they find out they are infected, they can trace back to their previous partners.

How can targeting MSM with HIV-HCV coinfection save money and resources?

Before we began this initiative, we also looked at whether implementation of early HCV therapy was cost effective or maybe even cost-saving. Our country has an agreement with pharmaceutical manufacturers that was adequate in lowering cost. The price used to be around 40,000 for 12 weeks, but since the new prices are ‘kept secret,’ the exact costs are unknown at the moment. Most likely, they are lower. A 12 weeks’ course of HCV therapy at the price of 40,000 was cost effective over a period of 40 years, if we lowered the price to 20,000, the HCV therapy was cost saving over a period of 40 years.

Before November 2015, we didn’t treat all patients with HIV/HCV coinfection. After that, we decided to treat all patients regardless of fibrosis state. In the near future, 75% of our cohort will be HCV-free. However, this is still ongoing.

Boerekamps highlighted some key data sets describing the success or potential success of their program.

On reducing new infections:

Rijnders et al. reviewed data from 17 HIV treatment centers from several regions across the Netherlands. Approximately 80% of HIV-positive MSM in the country undergo therapy at these centers. Before DAA therapies became available in 2014, data showed 93 cases of acute HCV in 8,290 person-years of follow-up from these centers (11.2/1,000 PYFU; 95% CI, 9.1-13.7). In 2016, this had decreased to 49 cases in 8,961 person-years of follow-up (5.5/1000 PYFU; 95% CI, 4.1-7.2). The researchers noted that this is a 51% decrease in new infections. This reduction in number of new HCV cases coincided with the uptake of DAA in this patient group.

Impact of unrestricted access to therapy:

Unrestricted access to DAA therapies began in November 2015. The researchers noted that unrestricted access means that all patients can be treated immediately, regardless of fibrosis status. Boerekamps et al. analyzed data for 22,042 individuals with HIV, of whom 1,812 had HCV coinfection. There were 1,420 patients still in care at an HIV clinic. Results indicated that 70% of patients overall were cured or expected to be cured for HCV, while 76% of coinfected patients may reach this outcome.

PAGE BREAK

Model for treating HIV-positive MSM treated before fibrosis:

If all diagnosed patients coinfected with HIV between 2015 and 2030 received DAA therapy, assuming a cure rate of 89% or higher, a model by Hullegie et al. showed a potential reduction in incidence rate from 12 per 1,000 person years to 5 per 1,000 person-years. This compared to a stable incidence rate of 12 per 1,000 person-years for treating patients with F2 or F3 fibrosis. A reduction in prevalence from 5% to 1.4% may also occur, compared with a 6.5% increase for treating at F2 fibrosis or a 7.6% increase for treating at F3 fibrosis. In terms of cost savings, treating these patients will incur a 31 million price tag, which accounts for 27,000 per infection averted. The researchers noted that the cost would be 39 million for deferring to treat at F2 or F3 fibrosis. They added that the economic impact of this strategy depends on the cost of DAA therapies.

On screening patients quarterly:

Lastly, they examined the cost effectiveness of screening four times a year in the general population and the target patient population of HIV coinfected individuals. Currently, this group undergoes ALT measurement twice yearly and antibody testing once a year. At this rate, it is estimated that the incidence rate of new infections would be 5.2 per 1,000 person-years after 10 years. ALT screening every 3 months would reduce this to 4.5 per 1,000 person-years, while PCR screening would reduce this to 4.3 per 1,000. In terms of cost, Popping et al. said that ALT testing costs 2, while PCR testing costs 165. She suggested that implementing these testing programs will be cost-effective, particularly in terms of quality-adjusted life-years gained, if a group of previously infected patients is targeted. – by Rob Volansky

Disclosure: Boerekamps reports no relevant financial disclosures.