HIV and Hepatitis C (HCV)

 Last Revised: August 10, 2016

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Hepatitis C virus (HCV) is a disease that infects the liver. HCV can cause lifelong infection, and over time it can cause fibrosis (mild to moderate liver scarring), cirrhosis (serious liver scarring), liver cancer, liver failure and death.

HIV mostly infects CD4 cells, also known as T-cells. These white blood cells coordinate the immune system to fight disease. When your immune system breaks down, you can develop many serious, often deadly infections and cancers known as opportunistic infections.

HIV can worsen hepatitis C. Not only does HIV increase the risk of liver damage, but it can also speed up the onset of liver damage following infection. It is important for people who are coinfected with HIV and HCV to work closely with their health care providers in order to safely and effectively monitor and treat both conditions.

Am I at greater risk for HCV if I am HIV positive?
Hepatitis C is common among people living with HIV. In the United States, 20 percent to 30 percent of people living with HIV are coinfected with HCV. This means that about 225,000 to 330,000 people in the United States are living with both viruses.

Hepatitis C is blood-borne. To cause a new infection, HCV must pass from the blood of an infected person into the blood of an uninfected (susceptible) person. In other words, HCV is most easily spread through direct blood-to-blood contact. People who inject drugs who have shared needles or other injection equipment, including cookers, cotton and measuring syringes, are at the highest risk of being infected with HCV—between 50 percent and 90 percent of people who got HIV from injecting drugs are also infected with HCV. This is because both viruses can be spread easily through blood and blood products.

While sexual transmission of HCV is relatively rare, being HIV positive appears to increase the risk for acquiring hepatitis C sexually. During the past decade, outbreaks of sexually transmitted hepatitis C have been reported among HIV-positive gay, bisexual, and other men who have sex with men (MSM).

Researchers have found some common risks—along with HIV itself—that are associated with these sexually transmitted outbreaks, such as:

• Participating in group sex
• Finding sex partners on the Internet
• Rougher, longer anal intercourse (receptive and insertive)
• Receptive or insertive fisting
• Shared sex toys
• Non-injection drug use (nasal or anal)
• Having another sexually transmitted infection

HIV may increase the risk of sexually transmitted hepatitis C infection among women. HIV-positive women who have male partners who inject drugs are more likely to be coinfected with hepatitis C than HIV-negative women with male partners who inject drugs.

Coinfected women can pass hepatitis C to their infants during pregnancy, labor and delivery. The risk for mother-to-infant transmission of HCV ranges from 5 percent to 10 percent in women with HCV alone. HIV increases that risk to between 10 percent and 25 percent. Although antiretroviral therapy reduces the risk for HIV transmission from mother to child, it is not clear whether it lowers the risk of hepatitis C transmission. What's more, delivering a baby via caesarean section, compared with vaginal delivery, does not appear to reduce the risk of mother-to-child HCV transmission. Breast-feeding is known to transmit HIV, and it may increase the risk of HCV transmission when the mother is living with both viruses.

You may be at risk for hepatitis C and should contact your health care provider for a blood test if you:

• Were notified that you received blood from a donor who later tested positive for hepatitis C.
• Have ever injected illegal drugs—even if it was only once.
• Have ever gotten a tattoo or piercing in a non-professional setting where equipment such as ink, inkwells or needles are re-used and potentially unsterilized.
• Received a blood transfusion or solid-organ transplant before July 1992.
• Received a blood product for clotting problems before 1987.
• Have ever been on kidney dialysis.
• Have evidence of liver disease (for example, persistently elevated liver enzyme levels).
• Have had multiple sexual partners, or sexual contact with an HCV-positive person.
• Have an HCV-positive mother.

Some HIV-positive people can clear HCV by a strong immune response or with treatment. It is possible, however, for a person who ultimately clears the virus—either spontaneously or through treatment—to become reinfected with HCV.

What are the stages and symptoms of HCV?
Being infected with HCV does not necessarily mean that liver disease will occur. What's more, it can take several years—decades, in many cases—for HCV to cause life-threatening liver disease.

The Acute Phase
The first six months after HCV infection are known as the acute phase. Soon after HCV enters the body, it infects cells in the liver called hepatocytes. During the acute phase, only a small number of people (about 25 percent) actually experience symptoms of infection, such as fatigue, decreased appetite, nausea or jaundice (yellowing of the skin and eyes). Almost everyone with acute HCV will experience an increase in their liver enzymes, especially one called alanine aminotransferase (ALT), because some liver cells are being damaged. Sometimes ALT will skyrocket to 10 times the normal level. Since people who are taking HIV meds have their liver enzymes checked every three to six months, doctors have been able to identify cases of acute HCV in HIV-positive people who have no other symptoms of infection.

About 15 percent of HIV-positive people who are infected with HCV are able to clear the virus from their bodies without treatment. In medical speak, this is called "spontaneous viral clearance." This usually happens during the acute phase—or first six months—after becoming infected.

Some things can predict the likelihood of spontaneous viral clearance, regardless of HIV status. People who have a 2 log—or 99 percent—drop in their hepatitis C viral load after four weeks are more likely to spontaneously clear hepatitis C, as are people with the IL-28B CC genotype.

The Chronic Phase
The majority of people (85 percent) living with HIV who become infected with HCV have chronic hepatitis C—an infection that will stay with them for life unless they are successfully treated. In other words, if 100 HIV-positive people contract HCV tomorrow, 15 of them will clear the HCV from their bodies within six months, whereas 85 of them will remain infected with the virus unless they are successfully treated.

Some people live with hepatitis C for many years without developing liver damage or experiencing symptoms. Many people will have some signs and symptoms of liver disease, such as fatigue, nausea, muscle aches and abdominal pain.

Hepatitis C can cause mild to moderate liver scarring (fibrosis) or serious liver scarring (cirrhosis). It can also lead to a buildup of fat in the liver (steatosis), which worsens liver scarring.

Cirrhosis affects the way the liver works, and it increases the risk for liver failure and liver cancer. Between 1 percent and 5 percent of people with cirrhosis will die from these complications of chronic HCV infection each year, notably liver cancer or liver failure.

What are the symptoms of HCV?
Many people with chronic hepatitis C have no symptoms of liver disease. That is, they don't necessarily feel or look sick. If symptoms are present, they are usually mild, aren't very specific (some people simply say they're feeling "blah") and tend to come and go. These symptoms may include fatigue, pains of the upper-right portion of the gut, nausea, decreased appetite, muscle and joint pains and forgetfulness (often referred to as "brain fog").

If hepatitis C begins causing serious liver damage or cirrhosis, symptoms may become more prominent. In addition to fatigue, there may be muscle weakness, poor appetite, nausea, jaundice, weight loss, itching, dark urine, fluid retention, abdominal swelling and ankle swelling. For more info on HCV, read the Hep Lesson: "How is it diagnosed, and what tests are used?"

How does HIV affect HCV?
HIV increases the risk for—and can speed up the development of—liver damage from hepatitis C. People with fewer than 200 CD4 cells are more likely to have liver damage from hep C.
Other than being coinfected with HIV, a number of other factors can cause liver disease to progress faster in people living with HIV. These include:

• Being coinfected with hepatitis B virus (HBV) and HCV;
• Heavy consumption of alcohol;
• Being over the age of 40 years;
• Having fat in your liver (steatosis), which is usually associated with being overweight or heavy alcohol consumption;
• Being male; and
• The length of time you have been infected with hepatitis C.

Coinfected people and their care providers may need to select HIV meds carefully. Although the benefits of HIV treatment outweigh the risks, many medications used to treat HIV, including the protease inhibitors and the non-nucleoside reverse transcriptase inhibitors, are broken down (metabolized) by the liver and can cause liver injury, even in people who aren’t living with HCV. People taking ARVs should have their liver enzymes monitored regularly.

On the one hand, these particular drugs may worsen or speed up the liver disease being caused by hepatitis C. On the other hand, many experts think that treating HIV can delay liver disease progression by keeping the immune system strong.

Choosing HIV medications that are known to be easy on the liver and are less likely to interact with HCV treatments is the best solution. Be sure to discuss your options with your health care provider.

Coinfected people usually have higher HCV viral loads than people with HCV alone, but—unlike HIV—the hepatitis C viral load is not linked to disease progression or liver damage. Liver enzymes are not a reliable indicator of disease progression, because some people have liver damage despite persistently normal liver enzyme levels. 

Even though it happens more rapidly in HIV-positive people, hepatitis C progression varies widely among individuals. Researchers have found that about 25 percent of people coinfected with HIV/HCV have rapid fibrosis progression (meaning they progress two fibrosis stages over three to four years). Some researchers have reported moderate liver damage in HIV/HCV-coinfected people within a few years of HCV infection, but this is unusual. 

With the HIV population getting older thanks to ARV treatment for the virus, many coinfected people are developing cirrhosis. In general, HIV is known to double the rate of cirrhosis. Experts estimate that without HCV treatment at least 20 percent of coinfected people will develop cirrhosis 20 years after HCV infection and 40 percent to 59 percent of people will develop cirrhosis in 30 years. 

People with cirrhosis or end-stage liver disease are at high risk for drug-induced liver injury and may need to avoid—or use a different dose of—some HIV drugs.

Discontinuing HIV treatment can worsen cirrhosis in coinfected people. Although the three-year survival rate among HIV/HCV-coinfected people with cirrhosis is 87 percent, once liver failure (also called decompensated cirrhosis) occurs, the survival rate drops to 50 percent at two years. 

In fact, end-stage liver disease from untreated, or unsuccessfully treated, hepatitis C has become a leading cause of death among people with HIV in the United States and Western Europe, where there is widespread access to ARV therapy. Compared with people who have only hepatitis C, those with both HIV and HCV are more likely to experience liver failure—which is often fatal unless a transplant is performed. In one study, people infected with both viruses were 21 times more likely to die of liver failure than those only infected with HCV.
Is treatment available for HCV if I'm coinfected?
Having HIV does not affect a person's chances of becoming cured. The length of treatment, which ranges from 8 to 24 weeks, depends on the person's HCV genotype (genetic structure of the virus), whether or not they have been treated before, whether they have liver cirrhosis, and the level of virus in the body (known as viral load).

Successful HCV treatment is defined as an undetectable hep C viral load 12 weeks after completing treatment. This is called a sustained virologic response, or SVR. It is also abbreviated as "SVR12," based on the weeks that have passed since treatment. People who achieve an SVR12 are generally considered cured.

A cure typically stops the advancement of liver scarring (called fibrosis) and may even send it in reverse to an extent. Ridding yourself of the virus also reduces, but does not necessarily eliminate, the raised risk of future health complications resulting from hep C, including cirrhosis, liver cancer, liver failure and death. The risks of such outcomes are higher if someone is cured of hep C when they already have severe liver scarring or cirrhosis.

The American Association for the Study of Liver Diseases (AASLD) says that people with hepatitis C who are coinfected with HIV should be prioritized for HCV treatment.

There are a number of highly effective treatments currently approved by the U.S. Food and Drug Administration (FDA) to treat hepatitis C. Many others are being studied in clinical trials or are awaiting FDA approval. For details on these medications, click here. To check out the AASLD-recommended regimens for those who are coinfected with HIV, click here.  (The treatment recommendations are based on your hep C genotype and how well your liver is functioning. If you don't know your virus genotype or how well your liver is functioning, these are good things to discuss with your doctor.)

Drug-drug interactions
Some of the hepatitis C drugs have been shown to interact negatively with HIV antiretrovirals. This is called a drug-drug interaction. So it's important for you, your physician and your pharmacist to consider what HIV regimen you are taking, to make sure it is safe with the hep C medications you are going to take and to make any necessary adjustments. Luckily, with the number of HCV therapies available today, the opportunities for safe and effective treatment when someone is being treated for HIV are quite broad.

Identified drug-drug interactions between HIV antiretrovirals and the various HCV drugs, as described in the various medications' published prescribing information, include:

Daklinza (daclatasvir):

• Daklinza requires dose adjustment when used with ritonavir-boosted Reyataz (a decrease to 30 mg daily) and efavirenz (found in Sustiva and Atripla) or Intelence (etravirine) (an increase to 90 mg daily).

Epclusa (sofosbuvir/velpatasvir):

• Epclusa can be used with most antiretrovirals, but not efavirenz, etravirine, nevirapine, or ritonavir-boosted tipranavir.
• Because the velpatasvir in Epclusa increases tenofovir levels, when given as tenofovir disoproxil fumarate (TDF; found in Viread, Truvada, Atripla, Complera, and Stribild), using Harvoni in combination with any of these HIV medications should be avoided by those with reduced kidney function (determined by laboratory tests measuring creatinine clearance rate).
• Tenofovir alafenamide (TAF; found in Descovy, Odefsey, and Genvoya) may be an alternative to TDF during Epclusa treatment for patients who take cobicistat or ritonavir as part of their antiretroviral therapy.

Harvoni (sofosbuvir/ledipasvir):

• Harvoni can be used with most antiretrovirals, but should not be used with ritonavir-boosted tipranavir.
• Because the ledipasvir in Harvoni increases tenofovir levels, when given as tenofovir disoproxil fumarate (TDF; found in Viread, Truvada, Atripla, Complera, and Stribild), using Harvoni in combination with any of these HIV medications should be avoided by those with reduced kidney function (determined by laboratory tests measuring creatinine clearance rate).
• Because this effect may be more likely to occur when TDF is used with HIV antiretrovirals boosted with either ritonavir or cobicistat, Harvoni should be avoided when these HIV drugs are being used, unless the antiretroviral regimen cannot be changed and the urgency of treatment is high. Tenofovir alafenamide (TAF; found in Descovy, Odefsey, and Genvoya) may be an alternative to TDF during Harvoni treatment for patients who take cobicistat or ritonavir as part of their antiretroviral therapy.

Viekira Pak (ombitasvir/paritaprevir/ritonavir; dasabuvir):

• Viekira Pak should be used with antiretroviral drugs with which it does not have substantial drug-drug interactions. These are: atazanavir, dolutegravir, emtricitabine, enfuvirtide, lamivudine, raltegravir, and tenofovir.
• The dose of ritonavir used for boosting of HIV protease inhibitors may need to be adjusted (or held) when Vierkira Pak (which contains ritonavir) is to be used to treat HCV. The dose of ritonavir should be restored when HCV treatment with Vierira Pak is completed. The HIV protease inhibitor itself should be taken at the same time of day as Viekira Pak.
• Viekira Pak should not be used with darunavir, efavirenz, ritonavir-boosted lopinavir, ritonavir-boosted tipranavir, etravirine, nevirapine, cobicistat, or rilpivirine.
• Viekira Pak should not be used in HIV/HCV-coinfected individuals who are not taking HIV antiretroviral therapy.

Sovaldi (sofosbuvir):

• Aptivus (ritonavir-boosted tipranavir) should not be used with Sovaldi.

Olysio (simeprevir):

• Olysio should be used with antiretroviral drugs with which it does not have substantial drug-drug interactions. These are: abacavir, emtricitabine, enfuvirtide, lamivudine, maraviroc, raltegravir (and probably dolutegravir), rilpivirine, and tenofovir.
• Olysio should not be used with cobicistat, efavirenz, etravirine, nevirapine, or any HIV protease inhibitor.

Ribavirin:

• Combining with didanosine, stavudine, or zidovudine is not recommended.

Zepatier (grazoprevir/elbasvir):

• Zepatier should be used with antiretroviral drugs with which it does not have substantial drug-drug interactions. These are: abacavir, emtricitabine, enfuvirtide, lamivudine, raltegravir, dolutegravir, rilpivirine, and tenofovir.
• Zepatier should not be used with cobicistat, efavirenz, etravirine, nevirapine, or any HIV protease inhibitor.

When should I start treatment for HCV if I'm coinfected?
Deciding when to start treatment is a personal issue you should discuss with your doctor. But there are currently no reasons to delay treatment relating specifically to being coinfected with HIV. In fact, having HIV, because it can accelerate the progression of liver disease among those with HCV, may be a reason to begin treatment sooner rather than later.

HIV-positive people with acute HCV infection—meaning they have been infected for less than about six months—should consider prompt treatment. The reason for the urgency is that curing hep C may be accomplished in a shorter amount of time during acute infection than during the so-called chronic phase that follows.

To take advantage of the relative ease of treating and curing acute hep C, people with HIV who have ongoing risks for hep C infection, such as injection drug use or condomless anal sex, should be monitored regularly for changes in their liver enzyme levels and for hep C antibodies. They should be tested for hep C by what's known as a PCR test (which is more sensitive than the antibody test) if they have significant elevations of their liver enzymes, show symptoms of hep C or suspect a recent exposure.


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