A Reinfection With Hepatitis C
Benjamin Young, MD, PhD: Hello. I am Dr. Benjamin Young, Vice President and Chief Medical Officer of the International Association of Providers of AIDS Care. We are here in New York at the International Conference on Viral Hepatitis to have a discussion about reinfection with hepatitis C virus (HCV) and whether this might be a limiting factor in treatment and prevention programs.
I am very pleased to be joined today by Thomas Martin, who is an academic clinical fellow at the Chelsea and Westminster Hospital in London, and Natasha Martin, a theoretical mathematician from the University of Bristol.
The two of you gave a riveting panel discussion just a few minutes ago. I want to bring this discussion to our audience. We have seen tremendous advances in the options for the treatment of HCV. They offer many possibilities, including what we know about HIV treatment, as a way of preventing new infections and limiting the extent of the HCV epidemic.
Let's talk about some of your recent work on reinfection with HCV and what this means. How big a problem is it in your communities, and what do you know about how this affects the prospects of treatment as prevention?
Reinfection in Injection-Drug Users and Men Who Have Sex With MenNatasha Martin, DPhil: A recent meta-analysis looked at reinfection among people who inject drugs. It found that reinfection rates were actually relatively low. Among those with a history of injecting-drug use, reinfection with HCV after successful treatment was about 2 per 100 person-years. Among those who continued drug use after HCV treatment, reinfection rates were slightly higher, about 6 per 100 person-years. If you compare that with the primary incidence of HCV infection among people who inject drugs, that rate is actually quite low. The primary incidence is between 6 and 30 per 100 person-years. This indicates that reinfection rates are lower among those who have been treated. I would caution that there haven't been many studies. Only a few studies were included in the meta-analysis. The sample sizes were small and these studies were probably subject to substantial selection bias. We need more data on reinfection, but the evidence that we have says that reinfection rates are relatively low in this population.
Thomas C.S. Martin, MD: My work has been based more on HCV in HIV-infected men who have sex with men (MSM). The HCV epidemic is in its infancy in this population compared with people who inject drugs. Even fewer studies are available. From the few studies that we have, we know that reinfection is significant. In Amsterdam they found a very high reinfection rate -- about 15 per 100 person-years. In London, where we have replicated this study, we found a rate of reinfection following HCV treatment of about 9 per 100 person-years. Given the small numbers that are involved, these estimates have wide error bars. To put this in context the way that Natasha did, that would be approximately 5-10 times the baseline incidence rate of HCV among HIV-infected MSM. These people don't inject drugs; this is sexually transmitted HCV.
Dr Young: Clearly, HCV reinfection is happening, and I'm hearing that there are potential differences in different populations -- different risk factors or risk groups.
Dr. Natasha Martin: That is true. The risk for reinfection is often used to justify not providing treatment or a reluctance to provide treatment to drug injectors, but the data don't support that theory. Right now, it's unclear how these reinfection rates will affect treatment as prevention initiatives.
Dr. Thomas Martin: It's certainly in its infancy. People are treating HCV without guidance about how to manage reinfections, or about the impact of reinfections on factors such as cost-effectiveness and on overall HCV prevalence. That's where we are with MSM.
Does Better Treatment Encourage Risky Behavior?Dr. Young: We also talked about the impact of having direct-acting agents to treat HCV. In the HIV care arena, something we are very interested in is pre-exposure prophylaxis. One point of discussion about why we shouldn't implement pre-exposure prophylaxis for HCV is the idea that access to better-tolerated medicines will encourage people to be more risky or will encourage disinhibition of safe practices. Do you think that is going to be an issue here?
Dr. Thomas Martin: I would draw a parallel with the introduction of highly active antiretroviral therapy (HAART) during the HIV epidemic. A study in San Francisco showed an increase in high-risk behavior with the introduction of effective treatment for HIV. People are rightly worried that in hepatitis C we will see an increase in risk behavior. If the treatment is just pills for 12 weeks, then I think we would see a change.
Dr. Natasha Martin: It's not clear among people who inject drugs, mainly because we don't have a lot of evidence. The evidence that we have indicates that just engaging with healthcare and going through the treatment process often has very positive outcomes among injectors, as far as reduction in risk behavior and increasing access to healthcare after treatment. It remains to be seen, because the new drugs are easier and they are better tolerated. More people will be willing to undergo treatment. We will see people go through treatment who we don't see currently. It will be interesting to see what happens with them as far as reinfection. The evidence that we have shows that going through treatment has very positive benefits in this population.
Hepatitis C Treatment Often More Cost-EffectiveDr. Young: Natasha, you raised a very interesting point in your presentation, that the treatment of HCV in people who are injection-drug users is actually more effective than treating the non-drug injectors. Could you expand on that?
Dr. Natasha Martin: That was based on some work we did that looked at the cost-effectiveness of the treatment of injectors. In our analysis, we included the risk for reinfection, which you would expect reduces the cost-effectiveness of treatment of injectors. We also included a potential prevention benefit of treating those who have this ongoing infection risk. We compared that with treatment of those who had no risk for reinfection, but also no prevention benefit. It turns out that across the board, treatment of injectors was cost-effective. This was a United Kingdom analysis, and we looked at a variety of prevalence settings. Even in high-prevalence settings (60% chronic prevalence), the treatment of injectors would still be considered cost-effective. We also compared that with treatment of non-injectors. We found that in most settings, it was more cost-effective to treat injectors because of this additional substantial prevention benefit. The idea that treatment of injectors could be less cost-effective because of the risk for reinfection doesn't really hold true when you include this prevention benefit.
Dr Young: That is fascinating, because it runs counter to our intuition about who should be treated. Tom, as an academic clinical fellow, what should our clinical colleagues take away from this conversation?
Dr. Thomas Martin: The treatment is certainly effective for people who are actively injecting drugs. That was part of the ground shift that Natasha has been trying to achieve by saying that people who inject drugs can complete HCV treatment and remain clear of infection after they finish. We are trying to change the mindset of clinicians. That is probably the most important thing to take away, along with the fact that you will be having a larger population benefit.
It's going to be very interesting to see the translation to the MSM population as well. As Natasha said, if people remain at risk for transmission, you derive a greater population benefit. Many of the reinfections we see are in people aged 40-50 years. These are the people who remain at risk. Any treatment that has prevention benefit is likely to be quite significant in that population.
Dr Young: Thank you both. This has been a wonderful conversation. Thanks for making the journey across the pond to our conference here in New York. For the International Association of Providers of AIDS Care in New York City, I'm Dr. Benjamin Young.