Dr Fierer: In answering this question, we need to think about who is getting reinfected to be able to discuss what the risks are. Generally, we know that for people who are reinfected after a longstanding hepatitis C infection (those in the United States from the baby boomer generation, for example), the reinfection rate is extremely low (< 1 in 1000). This is typically a stable group that is not participating in activities that result in hepatitis C infection. This group is separate from those we know who are most at risk for getting primary hepatitis C (injectable drug users, HIV infected men who have sex with men and more recently HIV-negative men who have sex with men, and especially those taking pre-exposure prophylaxis against HIV infection). So, the sharing of injection devices and sexual transmission between men are high-risk groups. Those are the two groups that are most likely to become reinfected. There are other small exceptions, but generally, this is where we need to look. For the elimination of hepatitis C, we need to take care of the people who have had it for a long time (because they are also the people with more advanced liver disease) and it is clearly important to find and treat them so they are much less likely to become reinfected. We need to eliminate the pool of infection amongst those who are actively transmitting and therefore being reinfected.

 

Dr Fierer: For those with a sustained virological response, it is pretty straightforward. We have wonderful long-term data from both interferon-based treatment and from the direct-acting antivirals demonstrating that late relapse (that we are pretty sure are not reinfections) are extremely rare (approximately 1 in 1000). So we can generally say that viremia that becomes apparent after a demonstrated SVR12 is almost certainly going to be reinfection, especially in people who are in the high-risk groups I mentioned earlier. The more difficult part is distinguishing reinfection from treatment failure in people who have not yet gone 12 weeks after completing treatment. This is not common. My clinical experience is taking care of men who have sex with men in New York City getting hepatitis C, and significantly less experience in people who are injecting drugs, but generally transmission and reacquiring risks are reduced during the treatment period and immediately post-treatment, but that is not true for everyone. In my practice, I have seen a few men who have become viremic again before SVR12. Those cases are a little more difficult, but for the bigger picture, we can do sequencing and look for genotypes. In New York, it is 90% genotype 1, so we are not going to see many genotype switches even on reinfection. But after SVR12, you can pretty much assume that it is a reinfection, and then treat that new infection as if it is a new infection. It is quite simple in that sense.

 

Dr Fierer: The good news is that treatment of reinfection, especially if detected early, is one of our simpler processes. For those whose primary infection came a little later in life (injectable drug users, HIV-infected men who have sex with men) for whom we have cured that infection, and they have had a younger infection, tend not have as much liver disease. The reinfection, which we hope we had been screening for, may only be months old and still in the enhanced treatment response phase. This is the early hepatitis C treatment phase where treatment is more effective. In those cases, we do extremely well, even better (if it is possible to do better with these wonderful directing drugs), and bring about a cure with a shorter duration of therapy. I have published a few smaller studies including some of my cohorts as part of the ACTG done globally on short courses of therapy. We are now testing very short courses, as little as four weeks of glecaprevir/pibrentasvir, for early infection. This requires careful selection of patients. But this is essential for the elimination of HCV. We have to treat the people who are actively transmitting. That is the only way it will work. We don’t have vaccination. For injectable drug users, we have harm reduction, such as needle exchange and opiate substitution programs, which are proven to work. Put those together, harm reduction and early treatment, and we have a chance to eliminate hepatitis C by the WHO definition within this population group. It is a bit more difficult in men who have sex with men. We don’t have well-proven interventions yet to promote behavioral changes in that population. But it is essential to treat these people. There will be reinfections, and certainly if we are not treating those people who are most involved. Treatment should not be stigmatized. It is essential to treat transmitters. Faster is better, in public health terms, to prevent transmission of infections to others and incurring fewer costs on the healthcare systems in terms of number of cases and duration of therapy. Treatment of active transmitters means cost savings to the system. Active surveillance after treatment is needed that people will be willing to participate in, and on finding an infection, it can be treated immediately using the same drugs, even more effectively if treated early. At the same time, we as physicians have to address any unconscious or conscious bias against hepatitis C. As a physician, we have to want our patients to do well, and they should be treated as many times as they get infected. It is also a public health consideration. We don’t have second thoughts towards people with other infectious diseases that are sexually transmitted. If it is a person’s third case of syphilis, we don’t say that we are tired are treating that patient. That person needs to be treated, and also for public health reasons. We don’t draw the line on a second heart stent if the patient is still smoking, and so on. This is part of an important unconscious bias probably associated with the underlying reasons for the transmission and acquisition of the virus. It is important as physicians and public health advocates that we need to look beyond those personal things for the greater good of the population at large, and for the individual. Because, as physicians, that is what we are supposed to be doing.