Table of Contents
- What Is Hepatitis C?
- 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. For more information on HCV, including how it is spread, tests for HCV, and co-infection with HIV and HCV, see our article on Hepatitis C.
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
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).
The makers of Incivek removed it from the US market in the fall of 2014 due to poor sales and stiff competition from Solvadi (see below). Incivek continues to be FDA-approved and is still available outside the US.
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.
Daklinza and Harvoni
In August 2014, Daklinza (daclatasvir) received European approval for use with Solvadi in the treatment of hepatitis C. Daklinza (NS5A inhibitor) is made by Bristol-Myers Squibb. It works by interfering with a protein necessary for HCV to reproduce. Harvoni, approved in Europe in November 2014, is a combination of Solvadi (sofosbuvir) plus ledipasvir, both of which are produced by Gilead. Ledipasvir, like Daklinza, is an NS5A inhibitor. Daklinza acts on several HCV genotypes and not just on genotype 1 (most common type in the US and Europe). Harvoni is mostly active against genotype 1.
In December 2014, the FDA approved the use of Abbvie’s Viekira PakTM for treatment of chronic genotype 1 hepatitis C. The Viekira PakTM is an all-oral, interferon-free treatment including two types of tablets: (1) paritaprevir + ritonavir + ombitasvir, and (2) dasabuvir. One month later, the European Commission approved the same combination, known as Viekirax (ombitasvir/paritaprevir/ritonavir) and Exviera (dasabuvir). Paritaprevir is a boosted protease inhibitor; ombitasvir is an NS5A inhibitor; and dasabuvir is a non-nucleoside NS5B inhibitor. This triple DAA combination works against HCV at three different stages of its lifecycle to keep the virus from multiplying and may be given with or without ribavirin.
In January 2016, the FDA and Health Canada approved the use of Merck’s Zepatier, a once-daily pill containing the protease inhibitor grazoprevir and NS5A inhibitor elbasvir to treat chronic HCV (genotypes 1 and 4) in adults, including those living with HIV. Like the Viekira Pak, it is an all-oral, interferon-free treatment that can be taken with or without ribavirin. Treatment with Zepatier, however, involves only one pill taken once daily.
New Drugs in the Pipeline
There are also several HCV drugs and new combinations of recently approved drugs in the development process. The treatments currently being studied are interferon-free, direct-acting antiviral combinations.
In April 2014, the World Health Organization (WHO) released 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.
The 2015 clinical treatment guidelines released by the European Association for the Study of the Liver (EASL) recommend that HCV treatment be prioritized in people living with HIV and HCV. Moreover, the EASL suggests that HCV treatment be prioritized regardless of the degree of liver cirrhosis (scarring). It recommends interferon-free treatment regimens when possible, in part because they are more effective in curing HCV, and in part because they have fewer side effects. Lastly, the EASL guidelines recommend that those co-infected with HIV and HCV receive the same treatments as those with HCV alone (mono-infected).
The British HIV Association (BHIVA) issued a January 2015 update to its treatment guidelines. This update includes recommendations that (1) all people infected with HCV receive treatment, regardless of the level of liver injury, and (2) DAAs should form the backbone of treatment and interferon should be avoided if possible.
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.
Incivek and Victrelis
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 and Solvadi
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.
Daklinza and Harvoni
Daklinza can cause nausea, headache, and fatigue (extreme tiredness). Harvoni can cause headache, difficulty sleeping, and fatigue. Both appear fairly well tolerated.
The drugs in the Viekira PakTM – paritaprevir + ritonavir + ombitasvir, and dasabuvir – can cause fatigue, nausea, itching, skin reactions, trouble sleeping, and muscle weakness. It is important to know that the Viekira PakTM can cause increases in liver function tests, especially among women taking products that contain a form of estrogen (female sex hormone) called ethinyl estradiol. This is most commonly found in birth control products (e.g., the pill, patch, ring). These products must be stopped before taking the Viekira PakTM and another birth control method used during treatment with this combination of drugs for HCV.
The most common side effects of Zepatier are tiredness, nausea, and headache. Zepatier can occasionally cause increases in liver function tests, and is not recommended for people with moderate or severe liver disease. It is also not recommended for people already taking several HIV protease inhibitors and/or products containing efavirenz (e.g., Sustiva, Atripla).
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.
Studies have shown that the two new HCV drug combinations of Daklinza + Solvadi and Harvoni – both of which contain neither interferon nor ribavirin – are highly effective in curing hepatitis C in people co-infected with HIV and HCV. After 12 weeks of treatment with the combination of Solvadi and Daklinza, 96 percent or more of co-infected people were cured of HCV. The same 96 percent cure rate was also seen in clinical trials of Harvoni. Notably, cure rates with Harvoni were lower among black individuals, and researchers are exploring why that was true.
The drugs that make up the Viekira PakTM – paritaprevir + ritonavir + ombitasvir, and dasabuvir – have shown that they cure genotype 1 HCV in 90 to 100 percent of those who take it. The combination appears effective in those co-infected with HIV and HCV as well as in those with liver cirrhosis (scarring) and liver transplants.
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. Generally, the benefits of being on HIV treatment outweigh concerns about liver injury from HIV drugs.
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 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.