Can treatment as prevention work for hepatitis C?
The advent of better drugs has helped increase interest in treatment as prevention for hepatitis C (HCV). With tomorrow's #WorldHepatitisDay drawing global attention to the condition, David Rowlands examines the issues and the responses to his latest online poll, which asked whether rates of HCV reinfection would increase in London over the next decade.
Encouraged by the results of using Treatment as Prevention (TasP) in human immunodeficiency virus (HIV), researchers are considering this as an approach to deal with widespread hepatitis C virus (HCV) infection. Part of the reason for the interest in TasP for HCV is that combinations of new, simpler, better-tolerated and interferon-free regimens have become available in many high-income countries in 2015.
The past decade has seen epidemics of HCV among men who have sex with men (MSM) with HIV infection in Europe, North America and Australia. These infections appear to be due to a combination of sexual risk factors. To what extent can TasP impact this rising trend?
HIV treatment path informs HCV
It was not until 30 years into the AIDS epidemic that the HPTN 052 study showed that early antiretroviral therapy reduced HIV transmission in serodiscordant heterosexual couples by 96 per cent. More recently, researchers with the PARTNERS study reported that no transmissions occurred among mixed-status heterosexual couples that did not use condoms if the positive partner was on HIV treatment with suppressed viral load.
Lessons learned from HIV have enabled faster progression of advances in the HCV arena. Next-generation direct-acting antiviral agents (DAAs) combined in interferon-free regimens are now routinely curing 90-100 per cent of clinical trial participants, including traditionally difficult-to-treat groups such as people with liver cirrhosis or HIV/HCV coinfection.
Given these promising results, researchers are asking whether prompt and widespread treatment could reduce HCV transmission, especially among groups with high incidence (new infections) and prevalence (total existing infections) rates, such as people who inject drugs (PWID).
The success of TasP for HCV would depend on a number of parameters, including chronic HCV prevalence and rate of treatment uptake in a local PWID population. These numbers can vary widely. Chronic HCV prevalence, for example, ranges from 25 per cent in Edinburgh to 50 per cent in Melbourne to 65 per cent in Vancouver.
Individual-level benefit favours treating the sickest patients first, but on a population level, treating someone earlier may not immediately benefit them, but could prevent many new infections.
HCV treatment for prevention among PWID
Substantial reductions in HCV prevalence among PWID cannot be achieved by harm reduction interventions, such as needle exchange and opiate substitution therapy, alone. Current HCV treatment is arduous and uptake is low, but new, highly effective and tolerable interferon-free direct-acting antiviral treatments could facilitate increased uptake.
Increased testing, earlier diagnosis, starting treatment sooner, drugs with higher cure rates, and improved treatment adherence have all played a role in reducing HCV incidence and prevalence among drug injectors.
Although potential TasP programmes assume that courses of HCV treatment will be relatively short, recovery from years of addiction does not occur in a few weeks. TasP programmes will need to help people who are recovering from HCV to understand the psychological drivers of their addiction, perhaps teaching basic life skills and, for some people, reintegration into wider society. If attention is not paid to addiction-related issues, it is possible that some people who are initially cured of HCV can have their addiction recur, become reinfected and/or infected with other germs, and/or develop different addictions in the future.
Access to more effective HCV treatment could halve new infections among MSM in the UK over the next decade but prevention may require long-term support for the community.
If 80 per cent of MSM are treated within a year of acquiring HCV, and 20 per cent of those with chronic infection are treated each year, incidence would be halved and the prevalence of HCV among MSM with HIV would fall below 3 per cent by 2025.
Studies of risk factors for HCV infection in MSM consistently show a strong association with unprotected anal intercourse, rectal bleeding, fisting and sex with multiple partners. The sharing of injecting equipment to inject methamphetamine and other stimulants during sex sessions has also been identified as a possible risk factor.
Recent studies in the UK and US show that the vast majority of men newly diagnosed with HCV have no history of injecting drug use.
Some studies have found that sharing straws for snorting drugs is associated with acute infection. A large study of HIV-positive MSM in the UK found that HCV acquisition was associated with a history of using the drug GHB and nitrites (poppers), both of which can be used during anal intercourse and sex parties. Sharing sex toys and ulcerative sexually transmitted infections, usually syphilis, have also been associated with acute HCV infection.
HCV incidence will only be checked among MSM and people who inject drugs by reducing HCV prevalence through curative treatment – TasP.
To estimate the potential effect of treatment on HCV incidence and prevalence in MSM in the UK, a model has been developed of HCV transmission among MSM using data from the United Kingdom Collaborative HIV Cohort (UK CHIC) and surveillance data on HCV infections.
The model assumed that 80 per cent of men treated within a year of infection (acute cases) and 35 per cent of men in chronic infection would be cured on interferon-based treatment, and that 90 per cent of all men treated with interferon-free direct-acting antiviral regimens would be cured. The model assumed as a base scenario that 39 per cent of newly-infected men would be treated each year, and that 5 per cent of chronically infected men would be treated each year.
Approximately 8.6 per cent of MSM with diagnosed HIV infection were estimated to have HCV in 2015.
If current trends continue, and rates of treatment of newly-infected men persist at a low level according to the base scenario, prevalence will increase to 10.8 per cent by 2025, assuming that HIV diagnoses also continue to rise over the same period. However, even a low rate of treatment would have an effect on prevalence. Without any treatment at all, prevalence would have reached 11.6 per cent in 2015 and would rise to 17 per cent in 2025.
Scaling up treatment to treat 80 per cent of newly-infected cases and 20 per cent of all chronic cases per year would reduce prevalence to under 3 per cent by 2025, and would halve new infections, to less than 0.5 per 100 person years of follow up.
A quarter of gay men in London are re-infected with HCV within two years of successfully completing treatment.
Despite efforts at reducing risk behaviour, HIV-positive MSM who clear HCV infection remain at high risk of reinfection. This emphasises the need for increased sexual education, surveillance and preventive intervention work.
Results from our most recent online poll showed 87 per cent of people agreed rates of HCV re-infection will increase in London over the next decade. Respondents commented:
Phil, 46, from London, diagnosed with hepatitis three years ago: "It will depend on access to new treatments. Treated people must be educated on how not to put themselves at risk of re-infection. Drug prices need to come down."
@QSusieg2: "Patients need to treat now to help stop the spread of the virus & clear the path & new Drug prices need to come down."
Adam, 24, from Birmingham, recently diagnosed with HIV: "There are more people with Hepatitis C now than ever before. It will increase in London and everywhere. It would help if they would treat patients with the new shorter treatment, more tolerable drugs. I think there will be more 'baby-boomer' cases coming to light. I think there would be more risks in the 60s /70s than drugs or blood transfusions. eg Dental & Vaccinations."
Studies have shown sexual re-infection of HCV in HIV-positive gay men in several large cities, such as New York, Paris, Amsterdam and London.
Although HCV is not generally regarded as a sexually transmitted infection (STI), more data is showing this may not be the case for people with HIV and particularly for sexually active HIV-positive gay men. Risk factors for transmission include active STIs, drug use, and types of sex that allow for blood-to-blood contact, including unprotected anal sex.
Acute HCV infections observed among HIV-negative gay men in London
HCV infections are occurring among HIV-negative gay men in London. Researchers at the Chelsea and Westminster Hospital identified 44 cases of acute HCV infection among HIV-negative gay and other MSM between January 2010 and May 2014.
HCV reinfection incidence and treatment outcome among HIV-positive MSM
Following the introduction of effective antiretroviral therapy (ART), liver disease has become the leading non-AIDS cause of death among HIV-positive individuals in the resource-rich world.
Routine screening for hepatitis C should continue for sexually active HIV-positive individuals even after successful treatment or clearance. Enhanced education efforts should occur in this population to highlight the importance of preventing re-infection.
Poll data
There were 126 respondents between 23 June and 17 July 2015, with data collected via online hosting at www.Design-Redefined.co.uk and social networking sites. The poll asked if rates of HCV re-infection would increase in London over the next decade. A total of 87.3 per cent agreed; 8.7 disagreed, while 3.9 per cent were unsure. Thanks to the members of the community for their input into the poll and this article.
The next poll examines HIV and growing older. View the poll and vote here.
About the author:
David Rowlands is the director of Design-Redefined.co.uk, delivering effective healthcare communications to professionals and patients.
His key objective is to design, develop and deliver community projects to enable people living with, or affected by, HIV and/or HCV to become better engaged with their treatment and care.
Working over a number of media platforms, across the public, private and third sector, he is able to establish a link to these sometimes hard-to-reach communities.
Contact David: Email: david@design-redefined.co.uk Twitter: @DR_tweetUK
Read about the previous poll:
