• Diagnosing HCV infection
• HIV/HCV Co-Infection: Twin Epidemics
• Treating HCV Infection
• In the Pipeline
• A Personal Testimonial
• Questions and Answers

What makes hepatitis C and HIV "twin epidemics"? Can hepatitis C transmission be prevented? Which should be treated first - HIV or hepatitis C? Hepatitis C has been on a lot of people's minds lately, and for good reason. Infection with hepatitis C virus (HCV) can cause severe liver damage, and is a serious health threat to people with HIV. At the first Community Forum of the new year, David Feldman, a gastroenterologist (a doctor who specializes in digestive system and liver diseases) from St. Vincent's Hospital, and Lillian Thiemann, Director of Educational Services for Community Prescription Services, provided practical advice for people living with HIV and HCV along with current HCV treatment information and a glimpse of treatments to come.

Dr. Feldman's presentation focused on three areas in hepatitis C: diagnosis, HIV/HCV coinfection, and HCV treatment options. He provided a frame of reference for his presentation with a few statistics. About 4-5 million people in the United States are infected with HCV, and 10,000 people die each year from the infection. Furthermore, about 40% of people living with HIV in New York City are coinfected with HCV, with disproportionally high coinfection rates among intravenous drug users. Not everyone infected with hepatitis C will progress to liver failure as a result HCV infection, in fact, fewer than 20% of infected individuals will reach this stage of HCV disease.

Dr. Feldman also briefly described routes of HCV transmission. HCV is a blood-borne virus, which means that it is transmitted through blood-blood contact. Needle-sharing is the most common mode of HCV transmission, but HCV can also be transmitted by sharing razors, toothbrushes, or cocaine-snorting implements. You may be wondering why HIV isn't also transmitted this way. Simply stated, HCV is a much "heartier" virus than HIV, and can survive out of the body longer. HCV transmission through sexual contact is possible, but is less likely than HIV transmission through sexual contact.

Diagnosing HCV infection
HCV infection can go undetected, as there are typically no symptoms until irreversible liver damage has occurred. In high-risk populations, adequate screening is crucial in order to diagnose, and if appropriate, to treat, HCV infection. This screening should consist of an HCV antibody test, a test that checks for the presence of antibodies to HCV. This test is similar to the HIV antibody test. Individuals who have a positive HCV antibody test should also have an RNA PCR test to confirm the presence of HCV. The antibody test may produce a false positive result, as some individuals manage to clear the virus after having a positive antibody test. The RNA PCR is used to determine HCV viral load, that is, the amount of HCV in the blood. The HCV viral load test is similar to its HIV counterpart, and is useful for the same reasons: to track disease progression and to influence treatment decisions.

Another test used to follow HCV progression is a liver biopsy, a procedure in which a small piece of liver tissue is removed in order to determine the severity of fibrosis (liver scarring) and/or cirrhosis (liver damage). A liver biopsy gives a gastroenterologist precise information about the state of the liver through direct examination of liver cells.

HIV/HCV Co-Infection: Twin Epidemics
Both HIV and HCV are chronic viral illnesses, and there are similarities in the mechanisms of viral reproduction (also known as replication) and acute infection. Both HIV and HCV replicate in the body at an incredibly fast rate. HCV has a half-life of 8 hours in the body, compared to HIV's half-life of 2 days. How does this affect replication? It drives HCV to replicate more rapidly than HIV in order to sustain itself, resulting in extremely high HCV viral loads, ranging from 100,000 to 5 million copies.

The extent of similarities between acute HIV and HCV infection is unknown, as HCV disease is not usually caught during acute infection. However, some researchers believe that the role of immune system killer cells is similar in acute HIV and HCV infection. If killer cells are effective in acute HIV infection, destroying large numbers of HIV-infected cells, the result is a low "viral set point." The lower the viral set point, that is, the lower the HIV viral load after acute infection, the slower the progression of HIV disease. If the situation is similar in acute HCV infection, it may be possible to lower the viral set point by treating HCV during this stage, improving overall prognosis.

So how does HIV infection affect HCV disease progression? And vice versa? Data gathered from 4,000 HIV-infected individuals indicates that liver failure due to HCV is the leading non-AIDS cause of death in people with HIV. Additionally, studies have shown that HIV worsens HCV infection -- individuals coinfected with HIV and HCV are about twenty times as likely to experience liver failure as individuals infected with HCV alone. There is no indication that HCV infection speeds HIV disease progression, however.

Treating HCV Infection
So now that we've talked about how to diagnose HCV and discussed some of the details of HIV/HCV coinfection, let's talk about treatments for HCV. What treatment options are available? What's in the pipeline? An excellent article entitled, "Interferon and Beyond: Treating HEP C" appeared in the Fall 1999 issue of CRIA Update. The article is a comprehensive HCV treatment information resource. We'll touch briefly on some treatment issues here.

Interferon, given alone or, more commonly, in combination with ribavirin, is the most common treatment for HCV. Interferon is a protein produced by the body that blocks viruses from infecting cells. The substance can be reproduced in the laboratory, and is usually dosed three times a week with daily ribavirin for six months to a year. Many medical providers are utilizing daily interferon dosing. Ribavirin is an antiviral agent that may block HCV replication once the virus has entered a cell. The interferon/ribavirin combination often decreases HCV viral load, lowers liver enzyme levels, and improves biopsy results. In some cases, treatment decreases HCV viral load below limits of detection, without viral rebound upon stopping treatment. Unfortunately, interferon can have severe side effects, including fatigue, joint and muscle pain, fever, chills, depression, hair loss and nausea. Side effects are usually most severe during the first few weeks of treatment. The main side effect of ribavirin is anemia (low red blood count). Ribavirin should not be taken by pregnant women or men and women engaging in pro-creative sex since the medication can cause birth defects.

Just as HIV mutates, resulting in drug-resistant strains, HCV can also mutate. If HCV is under pressure from medications that block replication, it will mutate at increased rates, forming treatment-resistant "quasi-species" in an attempt to preserve itself. These quasi-species have genetic material that is different from the original virus. The strains of virus that are treatment-resistant can survive and replicate in the presence of interferon and ribavirin. In a recent study, Gretch and colleagues showed that daily dosing of interferon leads to fewer quasi-species of HCV, which may make interferon more effective in the long-term. Daily dosing also increases the levels of drug in the body, making the drugs more effective.

Dr. Feldman offered several treatment guidelines:

• High interferon/ribavirin levels in the blood produce the best results in HCV treatment. Although interferon can be difficult to take, it should be dosed at the highest tolerable level.
• Longer treatment duration results in better outcome.
• Use high-dose induction therapy, that is, hit hard when you begin treatment.

In the Pipeline
The next thing in HCV treatment is pegylated interferon, which should become available this year. Pegylated interferon is produced by combining standard interferon with a waxy molecule. The combined substance stays in the bloodstream longer than standard interferon, can be dosed less frequently (once a week compared to three times a week), and may have fewer side effects.

But in Dr. Feldman's mind, the future of HCV treatment lies in helicase inhibitors. The HCV helicase is an enzyme that facilitates the unwinding of the virus' genetic material so that it can be copied in replication. When the action of the helicase is inhibited, the virus cannot copy itself, and replication is stopped in its tracks. Helicase inhibitors are currently in development, and may be available in 1-3 years. Other treatments that inhibit different enzymes in viral reproduction are also in development. Additionally, a major goal for researchers is the development of an effective HCV vaccine.

A Personal Testimonial
Lillian Thiemann spoke firsthand about coinfection with HIV and HCV. She reminded the audience that a productive and healthy life is possible in spite of coinfection. In her position as Director of Educational Services for Community Prescription Services, Ms. Thiemann promotes knowledge as the path to self-advocacy in treatment. Ms. Thiemann supplemented Dr. Feldman's presentation by offering suggestions for coinfected individuals, based on changes she made to promote her health.

Get vaccinated for Hepatitis A and B. Infection with hepatitis A or B, other viruses that can lead to liver damage, are both preventable with vaccinations. Infection with hepatitis A or B in addition to HCV is extremely dangerous but is preventable.

Avoid alcohol. Drinking alcohol will increase the rate at which liver damage occurs. Stay away from it.

Get a real understanding of what's going on in your body. Track your test results, read the publications that are available to you, talk with treatment educators about available options, and ask lots of questions. Figure things out so that you can advocate for yourself when you are in your doctor's office.

Support your body and your immune system through good nutrition and exercise. Eat healthy food, take vitamin supplements, and drink lots of water. Identify things or people in your life that motivate you to be healthy, and make positive lifestyle changes.

Understand your HCV viral load numbers, and don't freak out! A low HCV viral load is one million copies or less, and a medium to high viral load is two million to five million copies. Don't compare your HIV viral load to your HCV viral load, as they are two completely different measurements. HCV reproduces in the body at a higher rate than HIV, which explains the high HCV viral load numbers.

Q: What is the viral set point?

Q: If I am coinfected with HCV/HIV, should I have two different primary care doctors?

A: It has been shown that individuals who see an HIV specialist to treat their HIV infection have better outcomes than people who see a general practitioner. Although it has never been studied, it is likely that the same concept applies to treating HCV infection. If at all possible, enlist the aid of a gastroenterologist when tackling HCV.

Q: Please comment on the risk of hemorrhaging in the liver biopsy procedure.

A: Hemorrhaging is a very rare side effect of liver biopsy, and there are several steps that can be taken to reduce risk. Your physician can check your platelet count and bleeding time, and will give you medication to increase clotting if it's necessary.

Q: Does interferon cause hair loss?

A: Yes, interferon can cause temporary hair loss in some people. The good news is that your hair will regrow when interferon treatment is stopped.