"My doctors have warned me my health may be at more risk from HCV than HIV. I've been urged to have biopsies done of my liver and to consider going on treatment for HCV. I've decided to delay embarking on therapy for two main reasons: firstly, I have a genotype that is less responsive than others to therapy; and secondly, I don't want to take time out from work, which I'd probably need to do to accommodate the side effects. I like my life at the moment and I don't want that to change on the off-chance that I can clear the HCV. My current strategy is to wait until more effective drugs come along."
"Treating HCV to avoid the threat of future cirrhosis is a really good thing but, at the moment, I don't feel strong enough to try it. For me, maintaining a high CD4 count is a better way of protecting my liver."
"Six months after treatment I feel very lucky to have achieved a 'sustained virological response.' I know of other guys who have not been able to stick to the treatment, and others for whom it has failed. I had all the side effects during treatment, and it truly was the worst time in my life, but it was all worth it. All the side effects went away as soon as I finished the treatment, and I feel pretty much like my old self now."
"For me it was very important to have the HIV and HCV treated together -- they are related, and their progression is related. A liver specialist is not fully prepared to deal with somebody that lives with the double stigma of having these diseases ... and didn't really understand some of the social and psychological implications."
"I've heard about what happens in families during HCV treatment, people get so depressed, in such a mental state -- the husband or wife will say: I hate you ... because the people on interferon are so unbearable ... it's not worth it! There's no guarantee you'll get rid of it, or even get better -- get worse -- but your life can be ruined!"
For some people, deciding whether to do treatment is an easy decision; for most, it isn't. There are a lot of factors to be considered.
This section focuses on conventional treatment. Lifestyle-related choices that help your liver are covered later in the section, "Living With HCV/HIV Coinfection."
Deciding whether or not to treat hepatitis C is an individual and complex decision. Some people really need HCV treatment now. It may be a bridge until newer, more effective, and less toxic therapies are available. Medical need is one of several other factors to be taken into account.
You may know early on whether it is necessary to use the full course of HCV treatment. If, after 12 weeks, it looks like treatment will not work for you, you may decide to stop.
Treatment guidelines generally agree about when to treat, and who to treat, regardless of HIV status. Sometimes treatment is recommended more aggressively, such as for all coinfected people when "the benefits of therapy outweigh the risks."
Hepatitis C treatment is a combination of two drugs, pegylated interferon and ribavirin. Pegylated interferon is a man-made version of a chemical messenger made by the human body. Interferon stimulates the immune system to fight viruses, so it has antiviral and immunologic activity. Pegylation means that a small molecule has been attached to interferon to keep it in the body longer, to make dosing more convenient, and to render treatment more effective.
There are two types of pegylated interferon (PegIFN):
Pegasys is a liquid that comes in one vial and is stored in the refrigerator. Everyone uses the same dose of Pegasys, regardless of their weight. PEG-Intron is a powder that has to be reconstituted with purified water, both of which come in separate vials. PEG-Intron is dosed by weight.
Both types of pegylated interferon -- Pegasys and PEG-Intron -- have been studied in patients with varying severity of disease. They have not been compared directly, and so it is difficult to know whether one may be better than another in different circumstances.
Ribavirin is a nucleoside analog from the same family as many HIV drugs, but it does not work against HIV. On its own, ribavirin is not an effective treatment for hepatitis C; it needs to be used with pegylated interferon. It is given as a pill or capsule, twice daily. Ribavirin is usually dosed differently depending on body weight and genotype in HCV monoinfection, and often in HCV/HIV coinfection as well.
In coinfection, treatment is currently recommended for at least 48 weeks for all genotypes. Some doctors are extending treatment for people with genotypes 1 and 4.
Recent research has looked at tailoring treatment according to individual response. In particular, people who are HCV/HIV-coinfected may require a longer course of HCV treatment than those who are HCV-monoinfected, especially persons with HCV genotype 1.
The primary goal is to get rid of HCV -- treating to cure.
In hepatitis C, a sustained virological response, or SVR, means that a person does not have detectable virus in his/her bloodstream six months after completing hepatitis C treatment.
Most people who have had an SVR remain virus-free, although there have been fewer long-term studies of coinfected people than those with HCV alone.
Although some recent research has found very low levels of hepatitis C in the blood and liver tissue of some sustained virological responders, this small quantity of virus may not have any significant effect on liver health.
Improving Liver Health
A secondary goal of HCV treatment is to improve liver health by reducing inflammation, and sometimes, reversing fibrosis. This even happens in patients who do not have an SVR, although only in about half the number of cases.
In some cases, the condition of the liver may worsen after HCV treatment, particularly among people who did not clear the virus; the reasons for this are unclear.
Maintenance therapy (with full- or reduced-dose pegylated interferon, either continuously or intermittently) may provide people with serious liver scarring who do not respond, or who relapsed after HCV treatment, with a holding strategy until better treatments become available.
Long-term studies of people with HCV alone have reported that treatment reduces the risk of cirrhosis, liver cancer, and liver-related death, even in people who did not have an SVR.
For HCV/HIV-coinfected people, there may be an additional benefit from HCV treatment: less risk of liver-related side effects from HIV drugs.
Several factors can help you predict the likelihood of HCV treatment response, but the only way to know how you will respond is to treat. The most significant factors are:
|Evaluating the Response to Treatment|
The response to HCV treatment is measured by HCV viral load tests at different times.
SVR (Sustained Virological Response)
An SVR means that HCV is not detectable in blood six months after completing treatment. Many experts think of SVR as a cure, and it is an indication of long-term remission.
SVR rates are usually the most important results to look for from a clinical trial.
EVR (Early Virological Response)
An EVR means that the hepatitis C viral load has dropped by 99% (2 logs), or is undetectable after 12 weeks of treatment.
Someone who does not have an EVR has only a very low chance of getting an SVR (only 1% to 4% chance). Usually, people choose to discontinue hepatitis C treatment if they do not have an EVR.
Some people may switch to a lower dose of pegylated interferon to prevent HCV progression at this point (maintenance therapy).
ETR (End-of-Treatment Response)
An end-of-treatment response means that no hepatitis C virus is detectable by an HCV viral load test at completion of therapy. Some people with an ETR will see HCV viral load return, usually within 12 to 24 weeks after they have stopped treatment.
The term relapser refers to someone who has an EVR or ETR, but whose virus has rebounded and who didn't achieve an SVR.
Non-responder is a general term for someone who does not have an EVR, or if they stay on treatment for 24 weeks, does not ever have a 99% drop in viral load or undetectable HCV RNA while on treatment.
RVR (Rapid Virological Response)
Response to treatment after four weeks is called a rapid virological response (RVR). If HCV viral load is undetectable at this point, it is a good predictor of an SVR later. However, RVR is not good at predicting who is unlikely to respond, so treatment should not be stopped if there is no RVR.
RVR is currently only used in research.
Clearly, many factors are involved with response to treatment. The information in Table 4 is an overall snapshot of response rates from clinical trials of HCV treatment with pegylated interferon plus ribavirin.
The number of monoinfected and HCV/HIV-coinfected people who did not clear the virus during treatment is increasing. Strategies for re-treating HCV, such as using different types of interferon, higher doses of pegylated interferon and/or ribavirin, and a longer course of treatment, are currently being researched.
Generally, HIV treatment should be started first if the CD4 count is under 200 cells/mm3, and probably started first if it is between 200 and 350 cells/mm3.
There might be some circumstances -- perhaps when HCV treatment is likely to be used soon in someone whose CD4 count is already falling -- where HIV treatment may be started earlier. So long as HCV infection is stable, many people -- especially if they have been infected with HCV for a long time -- will treat their HIV first. Treating HIV may delay HCV disease progression by maintaining immune health.
In someone whose CD4 count is already strong (above 500 cells/mm3) there is no need to use HIV treatment before HCV treatment.
Using HCV treatment depends on:
Detailed information about HIV treatment is available from many different sources. For example, the i-Base "Introduction to Combination Therapy" deals with many questions (see "Resources and Further Information").
The most important aspects of HIV treatment are just as relevant in coinfection as in HIV monoinfection, including choice of treatment, adherence, side effects, and resistance. The main differences in considering HIV treatment for someone coinfected with HCV relate to timing (since some studies have found that coinfected people have a blunted CD4 cell response to HIV treatment), and concern about liver toxicity and damage as a side effect of HIV drugs.
Some HIV drugs are less liver-friendly than others, although it is not clear whether small increases in liver enzymes increase the risk of clinical disease. Caution is clearly important; ARVs should be selected carefully and liver enzyme levels monitored regularly.
(For more information, see "HIV Drugs and HCV Infection").
If HCV treatment is necessary, it is possible to treat people on a stable ARV regimen even if their CD4 count is less than 200 cells/mm3. Studies using an older form on interferon suggested that HCV treatment is less effective for people with low CD4 counts, but in more recent studies of pegylated interferon plus ribavirin, CD4 cell count does not seem to be a factor in the success of treatment, although the overall number of people with less than 200 cells/mm3 was small.
The advantage to treating HCV first if you have a strong immune system is that you can do this without worrying about drug interactions or increased risk of side effects from two sets of treatment.
If you clear HCV, it may also reduce the risk of side effects from HIV drugs when you use them in the future.
It is better not to start treatment for both HIV and HCV at the same time, because side effects can make each other worse.