Interventions drive down rates of hepatitis C among gay and bisexual men with HIV

• Some people living with HIV are also co-infected with hepatitis C virus (HCV)
• A Swiss program offered HCV testing and treatment to more than 4,000 gay and bisexual men with HIV
• Monitoring several years later found rates of HCV remained very low and continued to fall

Hepatitis C virus (HCV) infects the liver and causes inflammation in this vital organ. As chronic HCV infection sets in, healthy liver tissue is gradually replaced with scar tissue. Over time, the liver becomes increasingly dysfunctional and a variety of problems ensue. Some people develop persistent fatigue. Later, they can develop internal bleeding, fluid buildup in the abdomen and serious abdominal infections. Eventually, difficulty thinking clearly and problems with memory occur. Gradually, as the liver becomes increasingly unable to filter the blood of waste products, the skin turns yellow (jaundice). The risk of liver cancer rises as the amount of scar tissue increases. If HCV is left undiagnosed and untreated, it can result in death.

HCV can be detected with blood tests. Furthermore, the health of the liver can be assessed with additional blood tests and a specialized ultrasound scan called Fibroscan.

Several powerful HCV treatments are available in pill form. These can be taken once daily. Two commonly used HCV treatments are as follows:

• Epclusa – a pill containing two medicines, sofosbuvir + velpatasvir
• Maviret – a pill containing two medicines, glecaprevir + pibrentasvir

These drugs are associated with high rates of cure (95%) after a course of treatment (usually eight to 12 weeks, depending on the pill used). They are generally safe and well tolerated.

Routes of infection

In Canada today, the blood supply is screened, heat-treated and safe. Transmission of viruses such as HCV and HIV does not occur via blood transfusion or use of blood products (such as clotting factor). These days, in most high-income countries, new cases of HCV are most commonly spread via sharing equipment for drug use. Among some gay, bisexual and other men who have sex with men (gbMSM), HCV may also be passed through condomless sex and other practices that can injure the lining of the anus/rectum.

Elimination of HCV as a public health issue

In 2016, the World Health Organization (WHO) encouraged countries, regions and cities to help eliminate HCV as a public health issue by 2030. To achieve this outcome, public health authorities would need to reach the following WHO recommendations by that year:

• reduce new HCV infections by 90%
• reduce HCV-related deaths by 65%

Micro-elimination of HCV

In order to achieve these goals, public health authorities can help health systems focus on priority populations who have or who are at high risk for HCV infection. One such population is a sub-group of HIV-positive gbMSM (studies have found that some gbMSM with HIV are co-infected with HCV). Achieving HCV elimination in one population or sub-population is called micro-elimination.

To achieve HCV elimination goals, a number of strategies will need to be implemented, including the following:

• assessing rates of new HCV infections by making testing more accessible
• offering treatment to people with HCV
• providing advice about risk reduction
• increasing access to harm reduction services
• monitoring rates of re-infection among people who were once cured of HCV

A study in Switzerland

Researchers in Switzerland conducted an HCV micro-elimination program through a clinical trial called the Swiss HCVree Trial. In that study, researchers focused on gbMSM who were HIV positive. The trial had three phases over several years, as follows:

• screening phase – participants were offered HCV screening between 2015 and 2016
• treatment phase – if participants were found to have HCV, they were offered treatment and four sessions of counselling to help them understand and reduce their risk for reacquiring HCV
• re-screening phase – participants were offered HCV testing again in 2017 to see if there were changes to rates of HCV in the study population

During the treatment phase, 84% of people with HCV were cured. In the initial screening phase, about 5% of participants had HCV. By the end of the study, in the re-screening phase, 1.2% had HCV.

Subsequent testing and treatment

The Swiss HCVree Trial was of relatively short duration. In 2019, a couple of years after the trial ended, researchers with the Swiss HIV Cohort study (an ongoing study with people with HIV from across Switzerland) conducted routine HCV screening and subsequently analysed the results and medical histories of participants.

Among the 4,641 participants who were screened in 2019, only 0.6% had HCV (vs. 5% in 2015 and 1.2% in 2017). Thus, over time, rates of people with HCV fell significantly. This decrease over time was likely an effect of the original trial (Swiss HCVree) combined with continued offers of HCV testing and treatment after the trial ended. As there were fewer infected people, the risk of HCV transmission fell over time.

Thus, HCV screening conducted several years after a program of testing and treatment found that decreases in HCV infections were sustained. According to the researchers, the data demonstrate that efforts were “successful in curbing the HCV epidemic among MSM living with HIV in Switzerland.”

Switzerland’s successful micro-elimination results should encourage other countries, regions and cities to mirror the Swiss efforts in sub-populations such as gbMSM, particularly those with HIV.

Results

Researchers analysed blood samples that were collected in 2019 from 4,641 participants. These samples were assessed for active (replicating) HCV (hereafter called HCV infection). All participants were co-infected with HIV.

Lab test results revealed that 28 out of 4,641 men (0.6%) had HCV infection.

The cases of HCV infection in the 28 men were classed as follows:

• 11 were new – 9 men never had HCV before and 2 men were re-infected
• 17 men had previously been identified as having HCV

Among the two men who became re-infected, one had previously been cured with treatment and the other’s immune system had managed to contain and vanquish the virus on its own.

Common variants (subtypes) of HCV in the 28 men were as follows:

• genotype 1a
• genotype 4

Clues about health

To find out more about the participants’ health, researchers also had the blood samples undergo virological analysis for HIV levels (viral load) and immunological analysis (levels of CD4+ T-cells as well as levels of liver enzymes, suggestive of inflammation of the liver).

Participants whose blood samples collected in 2019 tested positive for HCV (vs. people who tested negative for HCV) were more likely to also have the following in their samples:

• detectable HIV
• lower CD4+ cell counts

The researchers also found that people with HCV were more likely to have elevated levels of liver enzymes in their blood.

Risk factors

Participants who had HCV were significantly more likely to disclose a history of injecting drugs (21%) than people who did not have HCV (3%).

Bear in mind

The research in Switzerland showed that a clinical trial offering HCV testing and treatment was a success among gbMSM who also had HIV. This effect was sustained for two years after the clinical trial ended.

Other studies in MSM

The Swiss researchers reviewed reports from a study in London. They stated that this study found a 68% decrease in new HCV infections among gbMSM who had HCV between 2015 and 2020 when a similar program of testing and treatment was offered. Significant decreases in HCV infections among gbMSM have also been reported from similar programs in Australia.

According to the Swiss researchers, “generalized screening programs combined with targeted intervention programs are needed to achieve early identification, access to treatment, and reduction in high-risk behaviour to prevent further infections in the long run.”

Complexity and challenges

The Swiss research underscores very promising trends toward HCV elimination. However, the researchers stated that their findings “also highlight the persistence and complex challenge of the ongoing HCV epidemic.” Although it was uncommon, some participants in the Swiss study remained infected with HCV, suggestive of issues with HCV treatment and adherence.

When researchers reviewed the medical records of people whose 2019 blood samples had HCV, they stated that “complicated medical histories, comorbidities, adherence problems and other risk factors play an important role [in] the care and prevention of HCV infections…”

The researchers stated that “despite the extensive harm reduction program in Switzerland, HCV infection through needle-sharing might still be a problem and might be linked to the increase in [sexualized drug use — “PnP” or “chemsex”] observed among MSM.”

The researchers encourage doctors and nurses to offer HCV screening to MSM who disclose PnP/chemsex, “even in the case of occasional use.”

The Swiss researchers are concerned that another sub-population of MSM—those who do not have HIV—may now be at heightened risk of HCV due to PnP/chemsex. Future efforts may need to be made to address HCV in gbMSM who do not have HIV or whose HIV is undiagnosed.

International connections

Switzerland is a tourist destination and travel hub that is located in the centre of Europe. Researchers found that two men in the study had HCV that was genetically related to variants in circulation internationally. They stated that if HCV transmission is to be eliminated in Switzerland, it also needs to be eliminated overseas.

Despite the issues mentioned, a program of testing and treatment in Switzerland found a high rate of success in reducing HCV infection among gbMSM who had HIV. This dramatic reduction of HCV in a sub-population should encourage other regions and countries to try to reproduce the Swiss success so that WHO goals can be achieved.

By Sean R. Hosein

Resources

Hepatitis C testing and diagnosis – CATIE

Curing Hepatitis C: what you need to know – CATIE

Three Canadian provinces not on track to eliminate hepatitis C by 2030 – CATIE News

Blueprint to inform Hepatitis C elimination efforts in Canada – Canadian Network on Hepatitis C

Action Hepatitis Canada

Hepatitis C – World Health Organization

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