Hepatitis C treatment for people with HIV

Effective direct-acting antiviral or 'DAA' medicines, used without interferon, can now cure most people with hepatitis C. This includes people who previously were considered to be more difficult to treat, including those with HIV co-infection, severe liver disease, prior treatment failure and people who use drugs.

DAAs attack hepatitis C at various steps of its lifecycle. Like HIV treatment, using a combination of drugs that work in different ways is more effective and prevents the development of resistance. But unlike current HIV treatment, hepatitis C treatment can lead to a permanent cure.

The newest DAAs cure more than 90% of people with chronic hepatitis C. Some can be taken as a once-daily combination pill, and some are active against all hepatitis C genotypes (known as 'pangenotypic'). They are well tolerated and treatment usually lasts just three months.

In comparison, the old standard of care – pegylated interferon alfa (Pegasys or PegIntron) plus ribavirin – required weekly injections, had to be taken for six months to a year, caused difficult side-effects including flu-like symptoms and depression, and only cured about half of treated people.

Because interferon-based therapy was so challenging, hepatitis C treatment was traditionally recommended mainly for people showing signs of, or at higher risk for, liver disease progression.

With the new drugs, however, many experts now recommend that everyone with hepatitis C should be treated, regardless of liver disease severity, and say there is little reason to wait. People with advanced fibrosis or cirrhosis need treatment most urgently.

Treatment is more effective when people have not yet developed severe liver disease. Early treatment can avert years of hepatitis C-related symptoms and conditions. Curing hepatitis C halts viral transmission, and studies are starting to show that widespread treatment is reducing new hepatitis C infections. But, due to their high prices, the new drugs are not available to everyone with hepatitis C in the UK and in many other countries. Treatment is prioritised for people with more advanced liver disease but co-infection with HIV may be considered a reason for earlier treatment.

Factors that affect treatment success

A number of factors can help predict how well hepatitis C treatment is likely to work for you.

Before starting treatment, it is important to have a test to see what genotype of hepatitis C you have. This determines which DAAs will work and predicts treatment response. Some DAAs are 'pangenotypic' or active against all genotypes.

There are at least six major hepatitis C genotypes. Genotype 1 is the most common type in the UK, Europe and the US. It has two subtypes, 1a and 1b. Genotype 1 was hard to treat with interferon-based therapy, but it can be successfully treated with all approved DAAs. However, genotype 1a is harder to treat than 1b.

Hepatitis C genotype 2 is less common worldwide. It responded best to interferon-based treatment, but is susceptible to fewer DAAs than genotype 1. Genotype 3 is the most common type in the Indian sub-continent and south-east Asia, but it is also found in the UK. Genotype 3 has been the hardest to treat with DAAs, but newer pangenotypic drugs are highly effective against it.

Genotype 4 is the most common type of hepatitis C in the Middle East and North Africa, but it has also been seen in hepatitis C outbreaks in the UK and Europe. Genotype 4 generally responds to the same DAAs as genotype 1. Genotype 5 and 6 are less common and less well studied.

Treatment is more effective during the acute stage of hepatitis C infection (the first six months), rather than after you have developed chronic infection. Some experts think it is best to start treatment during this stage because treatment is easier, and curing hepatitis C quickly prevents transmission. But others prefer to wait six months to see if the immune system will naturally clear the virus.

People with chronic infection are more likely to be cured if they are being treated for the first time than if they are being re-treated after prior unsuccessful therapy (known as being ‘treatment experienced’). However, most people can be successfully treated with DAAs regardless of their previous treatment history.

In addition to viral factors, the degree of liver damage and presence of cirrhosis also predict treatment effectiveness. People with cirrhosis have lower response rates, and those with very advanced or decompensated liver disease are more likely to experience complications during treatment. But again, most people with advanced disease can now be successfully treated.

Factors such as age, sex and race or ethnicity played a role in how well interferon-based therapy worked. For example, people of African descent had lower response rates than white people because they had a less favourable form of a gene called IL28B. But these factors have little or no impact on the effectiveness of modern DAAs.

Medications for hepatitis C

Direct-acting antivirals (DAAs) target different steps of hepatitis C reproduction. These include hepatitis C protease inhibitors, polymerase inhibitors and NS5A inhibitors. Recommended regimens include at least two drugs that work in different ways. Using a single medication alone can lead to drug resistance. Most DAAs are only available as part of a combination pill.

DAAs that are approved or nearing approval include:

• sofosbuvir (Sovaldi)
• daclatasvir (Daklinza) (may be combined with sofosbuvir)
• simeprevir (Olysio) (may be combined with sofosbuvir)
• sofosbuvir/ledipasvir (Harvoni)
• paritaprevir/ritonavir/ombitasvir (Viekirax) & dasabuvir (Exviera)
• elbasvir/grazoprevir (Zepatier)
• sofosbuvir/velpatasvir (Epclusa)
• glecaprevir/pibrentasvir (Maviret)
• sofosbuvir/velpatasvir/voxilaprevir (Vosevi).

The first-generation hepatitis C protease inhibitors, boceprevir (Victrelis) and telaprevir (Incivo), were approved in 2011. They were only effective against hepatitis C genotype 1 and had to be used with interferon and ribavirin. These drugs are no longer recommended.

All approved DAAs are effective against hepatitis C genotype 1 and most are also active against genotype 4. Sofosbuvir/velpatasvir or sofosbuvir plus daclatasvir are recommended for genotypes 2 or 3. Ribavirin may be added to combinations in some circumstances, such as for people with cirrhosis or previous treatment experience, in order to improve the chance of cure. It is taken as a twice-daily pill, with the dose usually adjusted based on body weight.

Treatment with DAAs usually lasts 12 weeks. Some easier-to-treat people – such as those with hepatitis C genotype 1b, low viral load and no cirrhosis who are being treated for the first time – can usually be cured with 8 weeks of treatment. On the other hand, people who are more difficult to treat may need to lengthen treatment to 16 or 24 weeks.

Current European treatment guidelines no longer recommend treatment that includes interferon. Nevertheless, funding restrictions in some countries, including parts of the UK, mean that interferon-based treatment remains the first-line option for previously untreated people with genotype 2. Some people with genotype 3 may also be treated with interferon on grounds of cost.

Newer drugs for the treatment of hepatitis C, such as the combinations of glecaprevir/pibrentasvir (Maviret) and sofosbuvir/velpatasvir/voxilaprevir (Vosevi) may become available in some parts of the UK in 2018, subject to funding arrangements.

Treatment outcomes

Hepatitis C is considered to be cured if the virus cannot be detected 12 weeks after completing treatment. This is called a sustained virological response (SVR).

Recommended DAA regimens that combine drugs from different classes have shown overall cure rates of 95 to 100% in clinical studies.

SVR rates are somewhat lower for treatment-experienced people and those with advanced liver disease. But some of the newest DAA combinations also have high cure rates for people with cirrhosis or prior unsuccessful treatment. Most people can be successfully treated, although some may need longer treatment or a regimen that includes more DAAs or ribavirin.

If you do not respond to treatment the first time, a second attempt may be successful. This is especially likely if you were previously treated with interferon and ribavirin and are now able to try DAAs.

Hepatitis C treatment that leads to a cure reduces the likelihood of developing cirrhosis and liver cancer. People who already have advanced fibrosis or cirrhosis may see some improvement or reversal of existing liver damage.

Taking treatment

It is important to take all doses of hepatitis C treatment in order to get the best results. Make sure you are ready to take a course of treatment by talking to healthcare workers about what is involved. Find friends and family who can support you while taking treatment. Other people who have already gone through a course of hepatitis C treatment can be a useful source of advice and support.

Side-effects of hepatitis C treatment

DAAs used in interferon-free regimens are well tolerated, with few side-effects. Overall, the most common side-effects in clinical trials of these drugs were fatigue, headache and gastrointestinal symptoms – usually mild and reported by a minority of participants. Most studies have seen few serious side-effects and few people stopping treatment because of them. Side-effects go away after treatment is completed, and health problems caused by hepatitis C, such as lack of energy and lack of concentration, should also begin to improve.

"Recommended DAA regimens that combine drugs from different classes have shown overall cure rates of 95 to 100% in clinical studies."

Although people with HIV and hepatitis C co-infection were prone to worse side-effects from interferon-based therapy, HIV-positive and HIV-negative people appear to tolerate DAAs equally well.

Current guidelines no longer recommend interferon-based therapy, with a few exceptions. Interferon can cause difficult side-effects including fatigue, fever and other flu-like symptoms, muscle or joint pain, nausea or diarrhoea, loss of white blood cells, skin rash, thinning hair and depression.

Some people have a better chance of being cured if they take ribavirin with DAAs. Anaemia is a common side-effect of ribavirin that can lead to fatigue and shortness of breath. Sometimes anaemia can be managed by reducing the ribavirin dose or using erythropoietin, a hormone that stimulates red blood cell production. Anaemia is less frequent when ribavirin treatment lasts for 8 or 12 weeks.

Ribavirin can cause birth defects or miscarriage (pregnancy loss) and must not be taken by women who are pregnant or thinking of becoming pregnant, or by their male partners. Couples in which one or both partners have taken ribavirin should avoid pregnancy and unprotected sex for at least six months after completion of treatment.

Treatment for people with HIV and hepatitis C co-infection

In the UK, standards for HIV treatment and care are set and monitored by the British HIV Association (BHIVA), the professional association for HIV doctors and other healthcare professionals. The most recent guidelines on HIV and hepatitis co-infection were produced in 2017 (see www.bhiva.org/hepatitis-guidelines.aspx). Experts now agree that treatment recommendations for people with HIV and hepatitis C should be the same as for everyone else with hepatitis C, so your treatment will follow national guidelines for hepatitis C treatment.

Like everyone else living with HIV, people with HIV and hepatitis C co-infection are advised to start antiretroviral treatment soon after being diagnosed with HIV. People with co-infection may particularly benefit from early treatment because having well-controlled HIV and restored immune function reduces the risk of liver disease progression.

Current guidelines recommend that everyone with HIV and HCV co-infection should start hepatitis C treatment with DAAs. Treatment is especially urgent if you have moderate or worse liver fibrosis (stage F2 to F4). But everyone with HIV and hepatitis C co-infection can benefit from early hepatitis C treatment because their liver disease may progress faster than it would in an HIV-negative person. Where there is a waiting list for treatment, people with HIV and hepatitis C co-infection are likely to be prioritised, especially if you have moderate or severe fibrosis.

People on antiretroviral treatment for HIV can be successfully treated for hepatitis C at the same time. Given the number and variety of HIV and hepatitis C medications now available, most people with co-infection can put together well-tolerated regimens for treating both viruses.

HIV treatment should not be interrupted in order to start hepatitis C treatment. However, you might need to change some of your HIV medications or use different doses of HIV or hepatitis C drugs to make sure that treatment remains effective and does not cause worse side-effects.

The following drugs or antiretroviral combinations have no problematic interactions with DAAs used in hepatitis C treatment:

• abacavir/lamivudine (Kivexa)
• tenofovir disoproxil (TDF)/emtricitabine (Truvada)
• tenofovir alafenamide (TAF)/emtricitabine (Descovy)
• rilpivirine (Edurant, also combined with TDF/emtricitabine as Eviplera and TAF/emtricitabine as Odefsey)
• dolutegravir (Tivicay, also combined with abacavir/lamivudine in Triumeq)
• raltegravir (Isentress).

If you haven’t started HIV treatment yet and have a low CD4 cell count (below 350), it is recommended to start HIV treatment first to improve your immune function. Once HIV treatment is started, it is important not to stop it, as studies have shown this can contribute to liver problems.

Some antiretroviral drugs can cause liver side-effects, and these may occur more often in people with liver disease due to hepatitis C. However, most widely used modern HIV drugs seldom cause serious liver toxicity. In addition, people with seriously impaired liver function may not be able to process HIV medications properly. Some drugs may require dose adjustments, while others should not be used by people with advanced liver disease.

The health of your liver should be regularly monitored during HIV and hepatitis C treatment.