Table of Contents
- What Is Hepatitis C?
- HIV and HCV Co-Infection
- Who Should Get Treatment?
- Treatment of HCV/HIV Co-Infection
- Side Effects of Treatment
- How Effective Is Treatment?
- Which to Treat First?
- Taking Care of Yourself
Hepatitis C is a disease of the liver caused by the hepatitis C virus (HCV). Over time, HCV can cause serious liver damage including cirrhosis (scarring), liver cancer, and life-threatening liver failure.
Because both HIV and HCV can be spread by contact with infected blood, many people are infected with both viruses. This is called co-infection. It is estimated that 12 million people worldwide are co-infected with HIV and HCV. In the US, about one in four people living with HIV (HIV+) are co-infected with HCV. Co-infection is even more common among HIV+ injection drug users, of whom about eight out of ten also have HCV.
HCV can progress more rapidly and lead to serious liver damage more often in HIV+ people. According to the US Centers for Disease Control and Prevention (CDC), having HIV more than triples the risk of liver disease, liver failure, and liver-related death due to HCV. Co-infection with HCV may also make HIV treatment more challenging. Therefore, it is important for HIV+ people to know whether they have HCV. The CDC recommends that all HIV+ people be routinely screened for both hepatitis B and hepatitis C. Many experts recommend that HIV+ people at continued risk for HCV be screened every year.
Treatment of HIV/HCV co-infection is complicated (for more information, see treatment section below). It is important to have a health care provider who is familiar with HIV and HCV to get the best treatment for both diseases. The good news is that HCV can be treated successfully, even in HIV+ people.
Not everyone who has HCV needs treatment. Among those who develop chronic HCV, many will not develop serious liver damage. Research shows, however, that HIV+ people are more likely to develop HCV-related liver damage and develop it faster than HIV-negative people. In addition, research shows that treating HCV earlier has a better outcome for those at risk for HCV disease progression and liver damage.
Health care providers look at a variety of tests and health-related factors when deciding whether or not to recommend HCV treatment. Treatment decisions are not based on symptoms alone, since the early stages of liver damage do not always cause symptoms or abnormal lab test results. Instead, health care providers consider any symptoms, your overall health, the results of liver enzyme tests, and the results of tests that determine the extent of any liver damage.
Tests for HCV include:
- HCV antibody and nucleic acid tests
If you have HIV, you should be tested for HCV. The standard HCV test is one that looks for antibodies to HCV in your blood. If your antibody test is positive for HCV, your body has been infected with HCV at some point in time. However, this antibody test can not tell whether you were infected in the past and got rid of the virus, or if you are currently infected.
If your antibody test is positive, you may also get a test for HCV RNA (the actual genetic material of the hepatitis C virus) called a nucleic acid test (NAT). If your NAT is positive, you are most likely infected currently infected with HCV. If your NAT is negative (no HCV RNA in your blood), then you were infected in the past and are not now currently infected.
If your antibody test is positive, your provider may get an HCV viral load. The HCV viral load cannot tell if or when someone with HCV will develop liver damage. However, the HCV viral load can help predict how well someone will respond to HCV treatment. Generally, the lower the HCV viral load, the better the chances that treatment will work well.
- Liver enzyme (or liver function) tests
Liver enzyme tests are blood tests that look at levels of liver enzymes. Because levels of liver enzymes can tell us how well the liver is working, liver enzyme tests are often referred to as liver function tests. Liver enzyme tests measure several things that the liver produces, including ALT, AST, bilirubin, albumin, and some indicators of your blood's ability to clot. Elevated liver enzymes may indicate liver damage. However, some people with HCV have normal liver enzymes, even in very advanced disease.
- Genotype tests
Worldwide, there are six different types of HCV called genotypes. These genotypes differ in their regional distribution and can predict how well treatment will work. Genotype 1 is the most common globally (six out of every ten infections) and is also the most common in the US. Genotypes 2 and 3 are less common in the US. Genotype 3 is very common in Southeast Asia, while genotype 4 is found mostly in the Middle East and central Africa. Genotype 5 is located almost entirely in South Africa, and genotype 6 is found in Asia.
Because different genotypes of HCV respond differently to different treatments, it is important to have a genotype test before you begin treatment. This will help you and your health care provider make decisions about which treatments to use and how long to use them.
- Liver biopsy
A liver biopsy (inserting a needle through the skin and into the liver to obtain a small sample that is examined under a microscope) is the most reliable way to determine how much damage has been done to your liver. It can also help you and your health care provider figure out when to start HCV treatment. However, a liver biopsy is not necessary in order to start treatment.
- FibroSURETM (or FibroTest)
FibroSURETM is a blood test that looks at six markers of liver activity to measure liver damage. It is often used as a non-invasive alternative to liver biopsy. This test is good at identifying either no liver damage or advanced liver damage. However, if the damage is somewhere between none and advanced, it does not give very helpful information. A liver biopsy gives more detailed information about all levels of liver damage.
FibroScan is a relatively new non-invasive test that is currently approved for use in 70 countries. In April of 2013, the US Food and Drug Administration (FDA) approved its use in the US. It is similar to an ultrasound, and is done in the office or clinic by your provider. The scan uses a dull probe that is pressed against the skin over the liver. FibroScan is used to measure liver damage and determine the stage of liver fibrosis. Because the sound waves it uses to measure liver damage must pass through body fat, it is not a good test for those who are obese, since its results are likely to be unreliable.
In general, health care providers are more likely to suggest treatment if you:
- want and are motivated to be treated
- have a liver biopsy or FibroSURE™ test that shows liver damage (inflammation, and particularly fibrosis)
- have early cirrhosis (scarring of the liver) but are not ill
- have HIV in addition to HCV
- are otherwise in good health or have other medical problems that are well controlled
- have acute hepatitis C (infected within the last six months)
There are also several factors to consider that have been shown to be associated with faster disease progression in HCV-infected people. Some of these factors include:
- Being older than 50
- Being male (most women with HCV do not develop liver damage as quickly as men)
- Using alcohol
- Co-infection with HBV or HIV
Treatment options for those infected with HIV and HCV have improved a great deal in recent years, and there are several promising new drugs in the research pipeline. In the past, the standard backbone of treatment was a combination of two medications:
- Pegylated interferon (Pegasys or Peg-Intron), taken by injection (shot)
- Ribavirin (Rebetol, Copegus), a pill taken by mouth
There are several different types of HCV, called genotypes. Genotypes 2 and 3 are easier to treat, while genotype 1 - the most common in the US - is generally harder to treat.
Victrelis and Incivek
In 2011, the FDA approved two new drugs for hepatitis C treatment: Victrelis (boceprevir) and Incivek (telaprevir.) Both drugs are HCV protease inhibitors and are considered direct-acting antivirals (DAAs).They work directly against the virus by interrupting HCV's ability to multiply or replicate. Both Victrelis and Incivek are taken in addition to the standard treatment combination of pegylated interferon plus ribavirin.
Studies of Victrelis and Incivek have shown that they interact significantly with some HIV drugs. Victrelis interacts with Norvir (ritonavir)-boosted protease inhibitors (boosted PIs). Because Victrelis and Norvir-boosted protease inhibitors are processed by the body in the same way, the two types of drugs can interact, or get in the way of one another. As a result, the HIV drugs may be less effective. The DHHS suggests that Victrelis not be used with boosted PIs; it adds that Victrelis should not be used with Sustiva (efavirenz).
Research on Incivek suggests that it can be given with Norvir-boosted Reyataz (atazanavir), unlike Victrelis. Incivek can also be given with Sustiva, but should be given at an increased dose when both are taken at the same time. Either Victrelis or Incivek can be given with Isentress (raltegravir).
Solvadi and Olysio
In late 2013, the FDA approved two more new drugs for chronic hepatitis C treatment: the nucleotide polymerase inhibitor Solvadi (sofosbuvir) and the protease inhibitor Olysio (simeprevir). Both of these drugs are also considered direct-acting antivirals that work by interrupting HCV's ability to multiply.
Olysio is given in combination with pegylated interferon and ribavirin. A protease inhibitor, Olysio has the potential to interact with other HIV drugs, including all non-nucleoside reverse transcriptase inhibitors (NNRTIs) and all Norvir-based protease inhibitors (PIs). Therefore, it will be important for your provider to ensure that it is used only with HIV drugs with which Olysio does not have significant interactions.
Solvadi is given either (1) in combination with pegylated interferon and ribavirin in those with genotypes 1 or 4 who have never taken HCV treatment (“treatment-naïve”), or (2) in combination with ribavirin for those with genotypes 2 and 3. For those with genotypes 2 or 3, this represents the first interferon-free HCV treatment regimen. It is recommended that Sovaldi not be used in combination with the HIV drugs Aptivus (tipranavir) and Norvir (ritonavir). However, it does not appear to interact with other HIV drugs, making it much more ‘user friendly’ than the new HCV protease inhibitors for people living with HIV and HCV.
If you or your provider has questions about potential interactions between any drugs you currently take and hepatitis C drugs, you may find the interactive drug chart at http://www.hep-druginteractions.org/ helpful.
New Drugs in the Pipeline
There are also several HCV drugs in the development process. In January 2014, study results were released showing that daclatasvir, when combined with Solvaldi, produces promising cure rates among genotypes 1, 2 and 3. This combination would be entirely oral (no shots!) and would include neither pegylated interferon nor ribavirin. Similarly, a small study of an interferon-free regimen of drugs showed promising results among those with genotype 1. Ledipasvir is another drug that, when combined with Solvadi, shows promising results for those with genotype 1, without either interferon or ribavirin. Other drugs in development include ABT-450, ombitasvir, and dasabuvir.
New Treatment Guidelines
In April 2014, the World Health Organization (WHO) released new guidelines for the screening and treatment of hepatitis C. These guidelines suggest that all people living in areas where hepatitis is common (“high prevalence areas”) be offered a HCV test. People who are co-infected with HCV/HIV can be treated with pegylated interferon + ribavirin + either Victrelis or Incivek or Olysio or Solvadi. People who are co-infected with HCV/HIV can also be treated with ribavirin + Solvadi.
Later in April, the European Association for the Study of the Liver (EASL) released new guidelines for the treatment of all subtypes of hepatitis C. These new guidelines move beyond the latest US and WHO guidelines and include a few key changes. First, the EASL guidelines recommend that those co-infected with HIV and HCV receive the same treatments as those with HCV alone (mono-infected).
Second, the EASL guidelines suggest that providers use a “mix and match” approach to treatment that includes several of the newest direct-acting antivirals. The EASL encourages providers to combine DAAs from different drug companies so that they can offer patients the most effective interferon-free HCV treatments. These DAAs include both Olysio, which has already been approved by the FDA and is scheduled to receive European approval in May 2014, and daclatasvir, which is expected to get European approval in September 2014. Solvadi already received European approval in January 2014 and US approval in late 2013.
Lastly, The EASL suggests that providers consider off-label uses for new DAAs and compassionate use of drugs not-yet-approved. Compassionate use refers to providers’ use of new, unapproved drugs to treat seriously ill patients when no other treatments are available or have proven ineffective.
Like most medications, the drugs used to treat HCV can cause side effects. The most common side effects of pegylated interferon include:
- Flu-like symptoms (fever, nausea, muscle aches)
- Anxiety or irritability
- Low white blood cell count (neutropenia)
While women tend to do better on HCV therapy than men, studies show that depression is more likely to affect women taking interferon. It is very important to speak to your health care provider about any side effects you are experiencing so he or she can help you manage them properly.
The most serious side effect of ribavirin is anemia, or a reduced number of red blood cells that carry oxygen throughout the body. This side effect can often be managed using a drug called Procrit or Epogen (erythropoietin or EPO).
Ribavirin can also cause serious birth defects. Do not take ribavirin if you are pregnant or planning to become pregnant, and stop taking ribavirin at least six months before becoming pregnant. Women and their male partners must use effective birth control while taking ribavirin. Many providers recommend that women use two forms of birth control to prevent pregnancy while taking ribavirin. Additionally, men taking ribavirin who have female partners are encouraged to use two forms of birth control since sperm exposed to ribavirin can cause birth defects.
Both Incivek and Victrelis commonly cause fatigue and nausea. Many people who have taken Incivek have also reported having a rash. For most people, the rash was mild and they did not have to stop taking Incivek. However, in a very few cases, the rashes were severe and life-threatening due to an immune reaction known as Stevens Johnson Syndrome. Many people who have taken Victrelis have also reported a bad taste in their mouth (this is called dysgeusia).
Incivek and Victrelis can also cause anemia. This is especially concerning because ribavirin can also cause anemia, and because anemia is already a common problem among HIV+ people.
Olysio, another protease inhibitor, can cause rash, itching, nausea, and muscle pain. It can also cause photosensitivity, or sensitivity to sunlight. Protecting yourself from the sun, either by using sunblock or limiting time spent outdoors, is suggested when using Olysio.
Solvadi can cause headache, difficulty sleeping, and fatigue (extreme tiredness). Overall, it appears to produce fewer side effects than the other drugs that have been recently approved.
Because the newer HCV drugs – Incivek, Olysio, Solvadi, Victrelis – are given in combination with ribavirin to treat co-infected people, the recommendations for use of any of these new drugs in pregnant women or women planning to become pregnant are the same as for taking ribivirin: do not take them if you are pregnant or planning to become pregnant, and stop taking them at least six months before becoming pregnant.
While treatment for HCV can be challenging, it may help to know in advance what side effects to expect. Various medications can help manage these side effects. Peer support groups can also help you get through treatment. And remember, unlike HIV therapy, HCV treatment usually lasts no more than six to 18 months.
Unlike HIV, successful treatment can cure HCV. Treatment success is measured in different ways. End-of-treatment virological response means HCV is undetectable in the blood at the end of treatment. Sustained virological response, or SVR, means HCV is still undetectable six months after the end of treatment. After this, the virus rarely comes back, and people are considered cured.
Research has shown that Victrelis and Incivek increased HCV treatment success among HIV-coinfected people who had never taken HCV treatment. However, Incivek and Victrelis must be taken with interferon, and both drugs make the side effects of interferon worse. Therefore, taking this combination of HCV drugs is very difficult, especially given that Incivek and Victrelis are also likely to interact with HIV drugs.
Olysio has also proven effective among those co-infected with HIV and HCV. While it has fewer interactions with HIV drugs, it still has to be taken with interferon. Solvadi, on the other hand, is effective enough to be given with ribavirin only (no interferon) for co-infected individuals with genotypes 2 and 3.
People receiving HCV treatment should have their liver function tests and HCV viral load levels monitored regularly, since this can show how well treatment is working. If your HCV level has not started to drop after 12 weeks of treatment, it is unlikely that the treatment is working, and your health care provider will probably advise you to stop taking the drugs. Sometimes a second round of treatment can lead to a cure even if the first attempt was unsuccessful. This is especially true if the first attempt used an older combination of HCV drugs. The newer drugs – Incivek, Olysio, Solvadi, and Victrelis – have increased the effectiveness of HCV treatment significantly.
For people infected with both HIV and HCV, research has also shown that adhering to HCV treatment predicts the best chances of SVR, or curing HCV. Adherence to HIV drugs is very important in keeping viral loads low, avoiding resistance, and maintaining good immune system health. We now know that adherence to HCV drugs is similarly important for the successful treatment and cure of hepatitis C.
People infected with HIV and HCV face some special treatment issues. Basically, significant liver damage makes it harder to tolerate HIV drugs. At the same time, some HIV drugs can cause liver issues. Therefore, there is some debate about whether to start HIV or HCV treatment first.
The current HIV treatment guidelines published by the US Department of Health and Human Services (DHHS) recommend that antiretroviral therapy for HIV be given to all co-infected people, regardless of CD4 count. However, since HCV treatment does not work well for co-infected people with CD4 cell counts below 200, HCV treatment is not recommended until their CD4 counts increase. For co-infected people who have never received HIV treatment and who have CD4 counts above 500, their providers may recommend delaying the start of HIV treatment until they have successfully completed HCV treatment.
The 2014 guidelines of the European AIDS Clinical Society (EACS) recommend that antiretroviral therapy for HIV be given to those co-infected people whose CD4 counts are less than 500. The EACS also suggests that those co-infected people with CD4 counts less than 350 wait to start HCV treatment until their CD4 counts improve.
The decision about which to treat first depends on many individual factors, including HIV viral load, CD4 cell count, and amount of existing liver damage. For this reason, it is important to see a health care provider familiar with both diseases whenever possible. As newer, improved HCV drugs are approved, barriers to treating HCV in the presence of HIV will drop as the benefits outweigh the consequences for more and more people.
In addition to medical treatment, there are steps you can take to keep your liver healthy, including:
- Eating a healthy diet
- Avoiding alcohol and street drugs
- Getting regular physical activity
- Getting vaccinated against hepatitis A and hepatitis B
Some herbs may help your liver, but others can cause serious liver damage. Be sure to tell your health care provider about any products you are taking, including over-the-counter or prescription medications, street drugs, herbal remedies, or nutritional supplements.