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Guide to Hepatitis C for People Living With HIV

Testing, Coinfection, Treatment and Support

August 2007

Managing and Treating HCV

"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!"

One approach is to decide first exactly what your priority is. Clearing the virus now is not the most important goal for everyone. In some cases, treatment may be more likely to improve the condition of your liver than to clear the virus. In other cases, treatment may not be necessary right away, or ever.

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 to Treat HCV

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.


Advantages of Using HCV Treatment

  • You can clear the virus.
  • Treatment can improve liver health by reducing inflammation. It may also reverse fibrosis. This can happen even in people who do not clear the virus, although less often.
  • It will stop the risk of passing HCV to sexual and drug-using partners.
  • Clearing the virus removes the risk of mother-to-infant transmission.
  • Treating HCV before starting HIV treatment will reduce the risk of liver toxicity from HIV drugs.
  • The treatment period is likely to be only 12 to 18 months, not lifelong.
  • Treatment may reduce the risk of long-term complications, including liver cancer, even in people who do not clear HCV.


Advantages of Delaying Treatment

  • The major disadvantages to treatment are the side effects and the impact they may have on your life during the treatment period.
  • Occasionally, the side effects can be so severe that they force you to stop treatment. In rare instances, you could be left with an illness after you stop treatment, such as thyroid disease or diabetes.
  • Some people have reported that the side effects have persisted, leaving them feeling unwell long after the end of treatment.
  • Treatment might not work for you.
  • There are many new drugs in development for HCV that may be more effective and easier to tolerate; however, they are unlikely to be available through clinical trials for at least five years. Trials for people with HCV alone usually begin earlier. Clinical trials in people with coinfection are likely to be delayed until after results from HCV monoinfection studies.
  • If your liver is healthy, you may be able to delay treatment.
  • If you are thinking of conceiving a child in the next year, consider delaying treatment, since ribavirin can cause birth defects. Men and women should take precautions to avoid pregnancy during HCV treatment and for at least six months afterward. Women who become pregnant on ribavirin need to discontinue HCV treatment. More information on ribavirin and pregnancy is available from the ribavirin pregnancy registry: www.ribavirinpregnancyregistry.com.


Who Needs HCV Treatment?

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."

  • HCV treatment is more effective when given during acute infection.
  • People with mild liver disease do not require treatment right away.
  • Treatment should be offered to people with moderate liver damage, since they are at risk of progression to cirrhosis.
  • People with compensated cirrhosis can be treated, but treatment is less likely to be effective, and side effects may be worse; careful monitoring is required.
  • People with decompensated cirrhosis cannot be safely treated for hepatitis C; a liver transplant is the best option.


How Is HCV Treated?

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):

  • alpha-2a (manufactured by Roche, trade name Pegasys), and
  • alpha-2b (manufactured by Schering Plough, trade name PEG-Intron)

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.


How Long Is a Course of HCV Treatment?

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.


Goals of HCV Treatment

Curing HCV

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

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.

Predicting the Response to Treatment

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:

  • HCV genotype (2 and 3 are more sensitive to treatment than 1 or 4);
  • HCV viral load (treatment is more effective with an HCV viral load below 400,000 IU/mL);
  • Race (treatment is less effective for African Americans; ongoing research is looking at this question);
  • Amount of liver damage and steatosis (treatment is less effective for cirrhotics and people with steatosis);
  • HIV status (treatment is less effective for HIV-positive people than for HIV-negative people);
  • Body weight (treatment is less effective for people who weigh more than 75 kg [165 lbs]);
  • Adherence to treatment, including maintaining the full dose of ribavirin and interferon at least 80% of the time; and
  • Effective management of side effects.


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.

Relapser

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

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.


Fig 2: Timeline for HIV-Positive People on HCV Treatment

Fig 2: Timeline for HIV-Positive People on HCV Treatment
Click to enlarge


How Well Does Treatment Work?

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.


Table 4: Sustained Virological Response (SVR) to Treatment per HCV Genotype

Table 4: Sustained Virological Response (SVR) to Treatment per HCV Genotype
Click to enlarge


Re-Treating HCV

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.


Should HIV Be Treated First?

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:

  • Your willingness and readiness to start HCV treatment, and
  • The need for treatment -- if liver disease is mild, HCV treatment can be delayed; if moderate to serious, HCV treatment is recommended.

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").


When Should HCV Be Treated First?

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.



  
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This article was provided by Treatment Action Group. It is a part of the publication Guide to Hepatitis C for People Living With HIV.
 
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