Hepatitis C Virus (HCV) and HCV / HIV Co-infection Handbook
National AIDS Treatment Advocacy Project
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Written by Jules Levin, Executive Director, NATAPContributions from Claire Wingfield. Medical Editor: Raymond T. Chung, M.D. Medical Director, Liver Transplant Program GI Unit Massachusetts General Hospital Assistant Professor of Medicine Harvard Medical School Boston, MA
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Table of Contents Page Number
Brief Facts and Statistics About Hepatitis C . . . . . . . . . . . . . . . . . . . . . . . .4
--What is Hepatitis C? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4
Facts on People with HCV Alone (monoinfected) . . . . . . . . . . . . . . . . . . .5How Can A Person Get HCV? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5What is Co-infection? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6Symptoms of Hepatitis C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7Diagnosis and Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .7
--Key tests: ALT, genotype, HCV viral load, biopsy
Liver Function Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8Genotype . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10The Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10HIV and HCV Similarities and Differences . . . . . . . . . . . . . . . . . . . . . . . 11Hepatitis Damages The Liver . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Why is the liver so important?
--Fibrosis, liver failure, liver cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . .13
Immuno-suppression associated with HIV appears to significantlyalter the natural history and clinical course of HCV . . . . . . . . . . . . . . . . .14Transmission of HCV . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14
-- Vertical Transmission (Mother To Child Transmission-MTCT) . . .14-- Heterosexual Transmission . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14-- Men Who Have Sex with Men . . . . . . . . . . . . . . . . . . . . . . . . . . . .15
Treatment for HCV and the Co-Infected Person . . . . . . . . . . . . . . . . . . .15
-- The Goals of Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15-- What is the Best Treatment for HCV . . . . . . . . . . . . . . . . . . . . . . .16-- Can HCV be "cured"? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17-- Expected Treatment Responses; Pegylated Interferon . . . . . . . . . . .17-- Study Results Tables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .19 - 21cccc-- Predictors of the Response to HCV Therapy . . . . . . . . . . . . . . . . .22-- Managing Side Effects of HCV Therapy . . . . . . . . . . . . . . . . . . . .22-- When to Begin HCV and HIV Therapy: HAART and HCV . . . . .23-- What is Maintenance Therapy? . . . . . . . . . . . . . . . . . . . . . . . . . . . .25-- Treatment Effect of Maintenance Therapy . . . . . . . . . . . . . . . . . . .26-- New Goal for HCV Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . .26-- New HCV Drug Research . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .26-- Vaccine Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27
Diet, Herbs and Vitamins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .27
-- Additional Alternative Approaches . . . . . . . . . . . . . . . . . . . . . . . . .27
Brief Facts and Statistics about Hepatitis C (HCV) What is Hepatitis C? The hepatitis C virus (HCV) is a liver disease caused by infection with the hepatitis C virus (HCV). HCV is spread by contact with the blood of an infected person, and can cause liver inflammation and scarring (fibrosis). Disease progression can result in increasing inflammation and scarring.
The body’s immune system is able to mount an effective response to most foreigninvaders. But as with human immunodeficiency virus (HIV), a person's immune sys-tem is usually unable to adequately respond to HCV. It is not yet clear how HCV isable to evade the immune response. It is believed that certain types of CD4 andCD8 cells (called cytotoxic T-cells or CTLs), which usually play a role for humansin producing an immune response to foreign invaders like a virus, are unable tomount an adequate response. It is believed that HCV-specific CD4 and CD8 CTLsplay a role for individuals able to clear HCV (about 15%) and for those whose dis-ease progression is delayed over time, or for those individuals who are able to mounta good response to treatment. It is also believed that like HIV, HCV is able to mutateto avoid the immune response.
About 1 million individuals have HIV in the USA, but about 4 million individualshave HCV -- about 1.8% of the entire US population (CDC statistics). Of those 4million about 2.7 million people have chronic HCV-infection.
The mechanisms by which HCV causes disease and damage remain poorly under-stood. The infected person's immune response to HCV may play a role in harmingthe liver by attacking HCV infected liver cells.
HIV may be a chronic manageable disease for many individuals, but end stage liverdisease is an increasing concern for people coinfected with HIV and hepatitis. Aspeople with HIV live longer, liver disease can progress, and HIV appears to acceler-ate HCV progression. You must pay attention to this. HCV-related liver failure canoccur even if HIV is under control with low HIV viral load and good CD4 counts.
HCV was initially identified in the late 1980s. Interferon was the only treatment forHCV, starting around 1990. It was the only known treatment until 1998 when rib-avirin and interferon were launched as combination therapy, doubling the responserates. The latest development in treating Hepatitis C is pegylated interferon (see page17). And, additional drugs and therapies are being researched.
A person’s HCV viral genotype and viral load are important to understanding theperson's ability to respond well to HCV therapy and in designing treatment strate-gies. (See Genotype Section on pg10 for better explanation). Facts on People with HCV Alone (monoinfected)
Eighty-five percent of individuals exposed to HCV develop chronic hepatitis C; onlyabout 15% clear the virus spontaneously within a few months of infection. OnceHCV becomes chronic it remains in the body unless successfully treated. It’s beensuggested that having HIV may impair clearance of HCV.
Not everyone with HCV monoinfection progresses to being sick. 20% of individu-als chronically infected with HCV monoinfection develop cirrhosis, (widespreadscarring & inflammation of the liver), which usually takes as long as 10-30 years todevelop. Once cirrhosis develops, liver cancer can develop at a rate of 1-3% per year,so after 5 years there may be a 15% chance of developing liver cancer (hepatocellu-ar carcinoma). 40% never progress and 40% progress over the course of 40-50 yearsif they live that long.
For many patients, serious complications of liver disease may not develop, and HCVmay not affect their lifespan. Some HCV-infected persons are at greater risk forfaster & more serious liver disease progression. Unfortunately, it is difficult to pre-dict who will progress more quickly. You can monitor liver disease progression byperforming a biopsy every 3-5 years. Other factors that may play a role in contribut-ing to faster liver disease progression include alcohol, IV and illicit drug use, andpoor diet. How Can a Person Get Hepatitis C?
• Intravenous drug use (IVDU), even once (IVDU is the leading risk factor for • HCV). If you use IV drugs even once with a needle containing microscopic •• amounts of infected blood transmittion is a risk. • Sharing IVdrug paraphernalia: microscopic amounts of infected blood can •• be present in cookers, used water, cottons, and on tourniquets. • Sexual intercourse with an infected person (low risk) see pg. 14• Tattooing with unclean needles or ink; body piercing (unknown risk)• Transmission from mother to child (low risk: but presence of HIV increases risk• of transmission) • Sharing a razor or toothbrush - blood exposure (low risk)• Blood transfusion before July, 1992 (high risk)• Needlestick accident with a patient with HCV • Hemodialysis• Other exposures to infected blood (moderate risk)
What is Co-Infection?
When a person has HIV and hepatitis C, it's referred to as co-infection.
The precise number of co-infected people in the United States has yet to be deter-mined. However, various studies estimate that approximately. 300,000 people withHIV are co-infected with hepatitis C (30%).
Intravenous drug use seems to increase the risk of co-infection because both HIVand HCV are transmitted by dirty needles. It's estimated that 60%-90% of peoplewho contracted HIV from IVDU also have HCV.
Hepatitis C progression appears to be more rapid in HIV-infected individuals com-pared to persons with HCV monoinfection. It is not yet clearly defined how muchmore quickly acceleration occurs, but several studies have found that progressioncould be as much as 2-5 times faster. The longer a person has had HCV/HIV themore likely it is that HCV has progressed. HCV is more easily transmissible thanHIV. Seventy to eighty percent of HCV infections appears to occur within the firstyear of IV drug use, so one may have had HCV longer than they have had HIV. Onesmall study suggests that intervention with HIV therapy (HAART) may slow or stopHCV progression for some individuals. This remains unproven. It is unknown ifHAART slows or accelerates HCV progression, or if it has no effect on progression. However HCV treatment may be very helpful in stopping or slowing progression. If a person has HIV, they should:
Be tested for HCV, hepatitis A and hepatitis B
If negative for A and B, they should talk to their doctor about getting vaccines forA and B.
Find a doctor(s) knowledgeable about both HIV and HCV, and start discussing treat-ment strategies for HIV and HCV. Show this handbook to your doctor and engageyour doctor in conversations about issues raised in this handbook.
Discussions about treatment strategies should include consideration of the benefitsand risks of immediate or deferred HCV treatment, and whether treating for HIVor HCV first is better on an individual basis. Symptoms of Hepatitis C
When a person is first infected with HCV, they may experience flu-like symptomssuch as malaise, fatigue, and weakness. But, often there are no symptoms. Withchronic infection, HCV usually progresses slowly for years and there are few symp-toms, until serious liver damage occurs. Some patients will develop non-specificsymptoms including mild fatigue and malaise, itching, and nausea. These symptomsare called non-specific because they may appear to be caused by other factors. HIVitself and HIV medications can also be associated with fatigue, malaise and nausea. Diagnosis and Testing Key tests: ALT, genotype, HCV viral load, and biopsy IF YOU HAVE HIV YOU SHOULD BE TESTED FOR HCV.
Despite having no symptoms, having HIV means a person is also in a high-riskgroup for having HCV, because both infections can be acquired in similar ways. People who contracted HIV through IVDU are at high risk for also having HCV.
Early detection means better options and outcomes.
Your lab tests for liver enzymes (ALT/AST) may be normal, but this does not meanyou do not have HCV, or progressing HCV liver disease.
The ELISA (Enzyme-Linked Immunosorbent Assay) antibody test indicates past or present HCV infection. A false negative test result can occur, particularly if a per- son’s CD4 count is <100. If you are in an obvious risk group (such as a former IVDU), you should re-test or consider performing a PCR viral load test, which tests directly for the presence of virus.
The RIBA (Recombinant Immunoblot Assay) test is used to confirm the presence of HCV infection.
When a person is at high risk for HCV (for example, an IVDU) it might be appro-priate to only test using the HCV-PCR viral load test, skipping over using the ELISAor RIBA tests; or to use the HCV-PCR test to confirm a positive antibody test. Liver Function Tests (LFT)
A key LFT is the ALT. ALT is a liver enzyme that is released by liver cells that areunder pressure, sick or dying. Thus, its presence in the blood indicates that the indi-vidual is suffering from liver damage or inflammation. In general, an HCV-infectedperson with normal ALT is considered to have mild or little liver disease. However,ALT may not always accurately reflect the liver condition. A person with normal orrelatively low ALT could have moderate fibrosis (in 10% of cases) or severe fibrosis(in 20% of cases). ALT levels should be monitored closely, as increasing levels sug-gest disease progression. High ALT levels in HCV-infected individuals suggest moreadvanced disease. HIV medications or other drugs can also cause elevations in ALT. A person with normal ALT and minimal/mild liver disease as determined by a biop-sy may want to defer treatment. However, close monitoring is recommendedbecause HCV may progress more quickly when HIV is present. AST (aspartate aminotransferase; serum glutamic-oxaloacetic transaminase; SGOT): This enzyme is made in many places throughout the body (heart, intestines, muscle), so an elevated AST alone cannot determine liver damage. It is often used to moni- tor liver disease in combination with other tests. An individual may be asked to fast for 4 hours before the blood sample is taken. ALT (alanine transaminase; serum glutamate pyruvate transaminase; SGPT): This enzyme is produced by the major cell found in the liver. Therefore, it is a good indi- cation of liver damage or inflammation. Increased ALT levels may be caused by all types of hepatitis or shock or drug toxicities. Therefore, as with each of these tests it must be evaluated in relation to other information. ALP (alkaline phosphatase): This enzyme is found in all tissues but is found in high concentrations in the liver, bile ducts and bone cells. There are different types of ALPs, therefore medical providers are able to distinguish ALPs from the liver and the bone cells. ALPs are used to determine the location of damaged or diseased tis- sues in the body. When assessing HCV, ALPs must be evaluated regularly to moni- tor liver damage or disease. The normal range is 44 to 147 IU/L. An elevated ALP or abnormal ALP may indicate damaged liver tissue due to HCV. GGTP (gamma glutamyl transpeptidase; GGT): These enzymes are found in the bile ducts and may be elevated by any type of liver disease. GGTP levels may be elevat- ed by heavy alcohol and drug use. Bilirubin: Oxygen is carried through the blood by hemoglobin. Red blood cells carry oxygen to the tissues by binding oxygen to hemoglobin. When red blood cells die, the hemoglobin is broken down to bilirubin in the liver. It is then excreted into
the bile and leaves the body in the feces. However, when liver function is decreased,there is a backup of bile in the blood and an individual may become jaundiced. Jaundice is a yellowing of the eyes and the skin, also urine may be very dark. Thisdoes not happen to all persons with elevated bilirubin. Persons with chronic infec-tion like HCV may maintain normal bilirubin levels until significant liver damage hasoccurred (i.e., cirrhosis). In persons with acute viral hepatitis (hepatitis A) the biliru-bin level is increased relative to the severity of the infection. The normal range forbilirubin is 1.1 mg/dl (milligram per deciliter) or lower. Elevations in bilirubin canoccur while taking Crixivan (indinavir), which is a protease inhibitor for treating HIV. Elevations due to Crixivan are usually transient. Albumin: Albumin is a protein that is manufactured by the liver and has a variety of functions, including transporting small molecules such as bilirubin and drugs in the blood. Another one of its main functions is to maintain fluid levels within the body. A person whose body has not received adequate hydration (fluids) may have a low albumin level. As the person rehydrates, the level will return to normal. A person who has hepatitis C and a low albumin level may suffer from a variety of conditions, such as edema (swelling in the ankles) or ascites (fluid accumulation in the abdomen) and pulmonary edema (fluid in the lungs). PT (prothrombin time; pro-time): PT is a test to determine the liver’s ability to pro- duce clotting factor. PT measures how long it takes blood to clot. When the liver is damaged, its ability to make clotting factors is impaired. Decreased clotting factor levels may increase the likelihood of bleeding. A prolonged PT indicates decreased liver function. A normal range is anywhere from 11 to 12.5 seconds, a PT of about 1.5 to 2 times the control value is considered abnormal (the control is usually about 11 seconds). HCV Viral Load: The PCR test can detect the presence of virus (HCV or HIV) in the blood, and can measure the viral load. The Roche qualitative HCV-PCR test only tells you if a person has above or below 50 copies/ml of viral load in their blood. The quantitative HCV-PCR tells you how much virus is present in the blood. There are three PCR quantitative tests, none of which have been FDA-approved: the Amplicor HCV Monitor (Roche), HCV Superquant (National Genetics Institute), and the Quantiplex HCV RNA test (Chiron). NGI/LabCorp offers a very sensitive HCV viral load test measuring as low as 2-10 IU/ml and up to as high as 100 mil- lion IU/ml. The Roche and Bayer quantitative tests have a lower level of detection of 600 and 615 copies/ml, respectively.
The viral load is considered along with a person's genotype in determining how longtreatment should be. In general persons with high HCV viral load ( >2 million) donot respond as well to therapy as persons with low viral loads, so they may requirelonger treatment. Genotype
It is important to do a genotype test because the HCV viral genotype can predict thepatient’s response to treatment and dictates the type and length of treatment. A per-son with genotype 1 or with > 2 million HCV viral load may need 12 months treat-ment rather than 6 months. In HIV-coinfected individuals, longer courses oftreatment are in general likely to be required. Genotypes refer to the genetic make-up of the virus. There are 6 major genotypes throughout the world. In the USA,genotype 1 is the most common (73%), and genotype 2 or 3 are the next most com-mon. In general, individuals with genotype 1 respond least well to therapy, whileindividuals with genotype 2 and 3 respond much better. Most individuals contract-ing HCV through IVDU have genotype 1. One large study showed over 90% ofAfrican-Americans had genotype 1. The genotype test is done from a blood sample. The Biopsy
If you are co-infected with HCV and HIV, I suggest you speak with your doctor about having a liver biopsy. Consult with a doctor knowledgeable and experi- enced in both HIV and hepatitis C. A liver biopsy may not always be necessary, but it is usually very important. The biopsy is useful in deciding when to begin ther- apy, what type of treatment a person will receive, and in evaluating how much and what kind of damage has been done to the liver -- it reveals the degree of liver inflammation and fibrosis, which helps predict when cirrhosis may develop. Generally, the treatment response rates are lower in people with cirrhosis, and com- plications and symptoms can develop after cirrhosis develops. If advanced fibrosis is identified by biopsy, treatment intervention may prevent or delay progression to cirrhosis. Because hepatitis C may progress more quickly in persons infected with both HIV and HCV, the information from a biopsy may be of more significance for persons who are co-infected.
When should a person get a biopsy? Some doctors feel that liver damage is minimalif the ALT is normal or low. However in co-infected individuals with moderate orsevere liver damage, ALT could be normal. A biopsy is the only way to truly assessthe stage of liver disease. A person could have high CD4s and undetectable viralload but still have cirrhosis. I suggest considering a biopsy as soon as a person isdiagnosed with HCV/HIV co-infection. The risk of complication from a biopsy islow (1-3%), and it should be a painless procedure. A well qualified doctor should beselected to perform the biopsy, as they will be better at minimizing discomfort andrisk for complication. Working with a highly qualified Gastroenterology andHepatology clinic can be helpful. HIV and HCV Similarities and Differences HIV and HCV Similarities: Both viruses are transmitted through blood. Ie.) sharing IV drug paraphernalia--nee- dles, cookers, used water, cottons, tourniquets with blood on it, etc. Any time there is blood to blood contact, HCV can be transmitted. Both viruses can evade the immune system, and both are resistant to eradication, but it appears as if HCV can be "cured" in some people. What is meant by "cure”? (See Treatment Section pg 15). Both viruses can mutate, although mutation rates appears greater for HCV because it replicates more quickly than HIV. The high mutation rates make eradica- tion and vaccine development more difficult. HIV and HCV Differences: CONSIDER EARLY HCV TREATMENT: In HIV, response to treatment may be better if treatment is started early in the course of the disease. But early HIV treatment also has downsides: HIV treatment can be for a lifetime or at least many years. So toxicities and side effects associated with HIV medications, as well as the need to follow often complicated treatment schedules or regimens, may be problems for as long as you take the medications. HCV treatment may also be more success- ful if started earlier. But HCV treatment is different in that it may be for a defined relatively brief period of time that may be limited to 6 or 12 months. Maintenance HCV therapy (see treatment section for explanation) may be ongoing or intermit- tent. You and your doctor should weigh the risks and benefits of immediate or deferred therapy. See “When to Begin Therapy pg 25 ” section of this handbook.
Viral load has a different significance with HIV than with HCV. You could have alow HCV viral load and have cirrhosis. HCV viral load does not appear to correlatewith liver damage, but in HIV a higher viral load means worse disease progression. In HIV, lower CD4 counts place a person at risk for infections and disease progres-sion. In HCV, a person's genotype affects the outcome of treatment.
HCV viral load can fluctuate more randomly and be less predictable than in HIV.
500,000 is high HIV RNA (viral load) but low HCV RNA (viral load).
In general individuals with >2 million HCV-RNA do not respond as well to HCVtherapy, while those with <2 million respond better.
HIV is better understood than HCV. HCV research is nearly 10 years behind HIVresearch. There remain many unanswered questions about HCV; HIV has beenresearched much more.
The currently approved and recommended standard of care for HCV is pegylatedinterferon plus ribavirin, but there are 17 drugs approved to treat HIV. Hepatitis Damages The Liver- Why is the liver so important?
Just as you cannot live without your heart or brain, you cannot live without your liver. Your liver performs many functions that are vital to survival. It transforms food intousable body chemicals. It filters waste, bacteria and poisons from your blood. Theliver stores vitamins and sugars that your body uses for energy.
The liver is a wedge-shaped organ located underneath the rib cage. Weighing closeto 3 pounds, the liver is the body's largest internal organ. It has four main functionsin the body: purification, synthesis, storage and transformation.
Following is an overview of the liver’s many roles:
Purification Your liver changes toxic substances, including alcohol, into harmless substances. Inactivation of substances like alcohol and nicotine is good for the body as a whole, but liver cells can be damaged in the process. For example, detoxification of alco- hol can lead to cirrhosis. Your liver also changes certain medicines into a form your body can use, and inactivates other medicines after they've worked, such as HIV drugs. If your liver enzymes are highly elevated, your liver may be having difficulty. Synthesis Your liver takes simple chemical building blocks and combines them to manufacture (synthesize) more complex substances. For example, the liver manufactures most of the proteins found in the blood, as well as those needed to clot blood, make new cells and cause chemical reactions inside of cells. Storage The liver is a warehouse for your body. Besides storing minerals and vitamins, the liver stores sugars that your body uses for energy. Your liver releases these sugars into the bloodstream between meals when other parts of your body, like muscles or the brain, need more energy. Transformation About 90 percent of the food you eat passes through your liver before it can be used. Your liver transforms food into vital body chemicals, including proteins, fats, and cholesterol. It also helps to digest fat and important vitamins carried in fats. When all of this is completed, your liver then sends this nourishment through the blood for cells to use. When your liver is not well The normal liver is smooth and firm to the touch. Progressive liver damage can lead
to fibrosis, shrinking and hardening, and formation of nodules. In cirrhosis, the livermay become small and hard, with extensive scarring and many nodules. Recent stud-ies found that cirrhosis can be reversible with HCV therapy for a percent of patients.
As mentioned earlier, hepatitis is an inflammation of the liver. Elevations in liverenzymes (ALT) may indicate that the liver is not doing well. As hepatitis progresses,inflammation and scarring of the liver increase. As liver disease progresses, otherchanges occur and damage to the liver increases. For example:
Fibrosis After becoming inflamed, the liver tries to repair itself by forming tiny scars. This scarring, called "fibrosis," makes it difficult for the liver to do its job. As damage continues, many scars form and begin to join together, leading to the next stage - cir- rhosis. Certain HIV medications can be hard on the liver. It is possible that certain HIV medications may contribute to HCV progression or liver damage, but this remains unclear. The liver is good at repairing itself, but there is only so much dam- age it can tolerate. Cirrhosis With cirrhosis, large areas of the liver become permanently scarred from repeated damage. The liver begins to shrink and become hard. Chronic viral hepatitis is a common cause of cirrhosis, as is alcoholism. Scarring prevents blood from flowing freely through the liver, severely impairing liver function. When a person has cir- rhosis, they are less likely to respond well to treatment. Liver failure As cirrhosis worsens, most liver function is lost. This means the liver is unable to filter wastes, toxins and drugs from the blood. It can no longer produce the clotting factors necessary to stop bleeding. Fluid builds up in the abdomen and legs, bleed- ing in the intestines is common, and eventually mental functioning is slowed. At this point, a liver transplant is the only option. Liver transplantation is a drastic last resort, and HIV+ persons have low priority to receive a liver. Liver cancer Sometimes damage to liver cells includes altering the genes inside cells in a way that causes them to become cancerous. Patients with chronic hepatitis B or C are at high- er risk for this form of cancer.
Early detection and consultation with a good doctor may prevent a person fromdeveloping the serious liver damage described above. Immuno-suppression associated with HIV appears to significantly alter the natural history and clinical course of HCV HIV accelerates hepatitis C liver disease progression. HCV-induced liver failure may occurmore quickly in HCV/HIV co-infection than in HCV alone. This accelerated pro-gression may be caused by the effect of HIV on the immune system, which mayeffect or impair how the immune system responds to HCV or therapy for HCV. Perhaps lifestyle may play a role-- years of IVDU or alcohol use may have harmedthe liver. The rate of HCV progression may vary from one person to another. Weneed more studies of HCV/HIV coinfected patients to better understand how andwhy HCV may progress more quickly in an individual, and to better understand thevariables.
It is uncertain what the effect of HAART is on liver disease progression. The resultsfrom one small study suggested that a protease inhibitor containing HAART regi-men can slow HCV progression. This remains unproven, and hasn’t been confirmedby additional studies. A different preliminary study suggested the opposite, that a PI-regimen may harm the liver. It remains unclear whether HAART can slow or accel-erate HCV progression, or whether HAART has no significant effect on liver dis-ease. Transmission of HCV
Potential routes for transmission of HCV are discussed on pg. 5. IVDU is the lead-ing cause of transmission for HCV. The overall transmissibility of HCV appears tobe higher in co-infected individuals than in those with HCV alone, perhaps due toHIV-induced immune suppression. Studies show that individuals with co-infectionmay have higher HCV viral loads, and this may be the cause for higher transmissi-bility of HCV. If a sex partner has HIV, this may increase risk of transmitting HCV. Does the presence of HCV increase the risk of HIV transmission? We do not havea clear answer to that question but it appears possible. Vertical Transmission (Mother To Child Transmission - MTCT) Some studies do not show an increased risk of HCV vertical transmission, but some studies do. There is a risk. One large study showed a 5% vertical transmission rate of HCV when only HCV was present in women, but 17% when the pregnant women were co-infected with HIV. Therefore, infection with HIV may increase the risk of HCV vertical transmission. Heterosexual Transmission The rate of heterosexual transmission has not been clearly determined. The risk appears low, but there are exceptions. Among long-term monogomous heterosexu- al partners of HCV-infected HIV-negative, several studies show a 0-3% risk of sex-
ual transmission of HCV. Having sex while a woman is menstruating may increaserisk for transmission. Anal sex may increase risk of transmission.
When HIV co-infection is present, several studies show 9-13% risk of HCV trans-mission to sexual partners. So, the risk of sexual transmission of HCV appears tobe increased when a person also has HIV.
This creates greater concern about HCV transmission rates in regions where HIV isspread primarily through heterosexual sex, such as in Africa.
High-risk sexual behavior also appears to play a role in sexual transmission of HCV. Any time blood is shared, there may be a risk of HCV transmission. Alcohol anddrug use may encourage risky sex behavior resulting in HIV and HCV transmission.
Studies show that individuals with multiple sex partners are more likely to get HCVthan those in monogamous relationships. Anal sex may damage the lining of therectum, and potentially facilitate blood to blood transmission. Men Who Have Sex with Men Several studies show there can be a risk of HCV sexual transmission for men who have sex with men. Sexual behavior that may draw blood may increase risk. The presence of sores or ulcers may increase risk. Sexual practices such as fisting or rim- ming may increase risk. Treatment for HCV and the Co-Infected Person
An HCV-infected person should ask his or her doctor the following question: what are my various strategies for when to begin HIV and/or HCV therapy, and what are my options for treatment? Each person's situation is different, and treatment deci- sions should consider the individual's situation, the potential outcome of treatment, and the disease stages of their HIV and HCV. In order to properly assess a person's HCV health status and potential outcome from treatment, certain lab tests need to be performed including: HCV viral load, genotype, liver function tests, and perhaps a biopsy. What is the primary goal of HCV therapy? To reduce HCV viral load to undetectable and normalize ALT/AST. What is the secondary goal of HCV treatment?
The secondary goal of HCV tre atment is to prevent progression of l iver disease. , a n dto improve the condition of the liver (improving infl a m m ation and fibrosis (scarr i n g ) . When the primary goal is not ach i evable the secondary goal becomes ve ry import a n t ,and may be ach i eved without a reduced viral load. What is the Best Treatment for HCV?
Combination therapy with interferon and ribavirin is considered the most effectivein reducing HCV viral load and improving liver enzymes (ALT/AST). Before 2001,the FDA approved regimen was interferon at a dose of 3 Million International Units(3 MIU or MU) administered by subcutaneous injections three times per week, plusribavirin pills taken twice per day (800, 1000 or 1200 mg per day). Ribavirin is anucleoside analogue like AZT or d4T, but it does not have activity against HIV. InJanuary 2001, a new form of interferon called pegylated interferon was approved bythe FDA (see Treatment section). Pegylated interferon is the new form of interfer-on (see next page).
Some doctors have been prescribing interferon in dosing schedules different fromthe standard of 3 MIU 3 times per week. Many doctors felt interferon should begiven more frequently, at least at the beginning of treatment, because interferon lev-els fall too low between dosing on the standard regimen. But study results with alter-nate dosing have been mixed. The introduction of pegylated interferon changestreatment options & strategies.
HCV therapy can be difficult to tolerat e. Side effects can incl u d e : fat i g u e, i rr i t ab i l i t y,d ep re s s i o n , a n e m i a , weight loss, loss of ap p e t i t i e, reduced platelet count, l ow wh i t eblood cell count and neutrophil counts, fl u - l i ke symptoms (ch i l l s, l ow grade feve rs,b o dy ach e s, h e a d a ches ), among others. For coinfected pat i e n t s, weight loss may ex a c-e r b ate lipoat ro p hy. Fl u - l i ke symptoms can improve by limited use of a c e t a m i n o p h e n( Tylenol) or A dv i l , and drinking plenty of d e c a ffe i n ated fl u i d s. M o re than 2000 mgo f Tylenol per day can cause liver tox i c i t y. M o re serious toxicities from HCV t h e ra-py are possibl e. Ask your doctor about these. For people with HIV, the most com-mon side effect seen with ribavirin can be anemia (reduced hemogl o b i n ) , wh i ch canbe effe c t ive ly tre ated with Procrit (EPO) therapy in many cases, while remaining onr i b av i r i n . H e m oglobin should be monitored cl o s e ly ; we e k ly during the first month oft re at m e n t . Dose reduction of r i b avirin for a brief period can also be considered fo rm a n agement of r i b avirin-induced anemia. A n e m i a , and reduced platelets and bl o o dcell counts can be reve rsed with tre atment or by stopping therapy. B e fo re star t i n gt re at m e n t , m a ke sure your doctor fully explains the potential side effects and tox i c i-ties (see page 18: h ow to manage side effe c t s ) . Ribavirin causes severe birth defects, therefore women who are pregnant should not take ribavirin. Women on HCV therapy who are considering pregnancy should wait atleast six months before conceiving. Those who become pregnant while tak- ing ribavirin should discontinue therapy immediately. Women and/or their partners who are taking ribavirin should use effective contraception (two different and reli- able forms) during treatment and during the 6 month post-treatment follow-up peri- od.
Patients with psychiatric or mental illness may have problems tolerating or adhering
to interferon. Depression can be a common side effect of interferon. Pre-existing
mood disorders can be treated before starting HCV therapy. The use of anti-depres-
sants can be used to treat depression before and during HCV therapy. Still, inter-
feron may not be recommended for individuals with clinical depression or who are
Can HCV be "Cured”?
HIV cannot be cured yet. But a number of doctors think HCV is "curable." Whatdoes "curable" mean? The goal of therapy is to reduce HCV viral load to unde-tectable and keep it there. Treatment for HCV may be time limited, unlike treatmentfor HIV. Standard HCV treatment is usually for 6 or 12 months. There are twotypes of treatment responses, End of Treatment Response (ETR) and SustainedVirologic Response (SVR). ETR is achieved when HCV viral load is undetectable(less than 100 copies per ml) at the end of treatment. SVR is achieved when the viralload remains undetectable at six months following treatment. A few small studieshave shown that 3-11 years after achieving a SVR, HCV viral load is still undetectablein almost all the patients. They call this a "cure." Does this mean there is no HCVanywhere in the person's body? We do not know the answer to this. But a smallstudy recently showed that if HCV was not found in the blood it could not be foundin the liver either. One recent study showed that viral failure (relapse) appears to onlyoccur within 2 years after stopping therapy. What Treatment Responses Can Be Expected?
Results from the following studies were conducted in patients with HCV monoin-fection (study patients did not have HCV/HIV co-infection). Two large studies froma few years ago found that about 40% of patients with HCV alone achieved an SVRusing the standard interferon regimen of 3 million units 3 times per week plus rib-avirin. In these studies, individuals with genotype 2 or 3 achieved an SVR 65% ofthe time, while individuals with genotype 1 had an SVR 29% of the time. Pegylated Interferon. Pegylation is a new form of interferon that is injected sub- cutaneously but only once weekly. What is the process of pegylation? A chemical molecule (synthetic polyethylene glycol) is attached to interferon. This delays the clearance rate of interferon and achieves higher sustained interferon levels in the blood. In concept, pegylation is similar to sustained release vitamins or medications. There are 2 pegylated interferons. Pegasys (peginterferon alfa-2a) is made by Roche and was approved in late 2002 for use as monotherapy or in combination with rib- avirin. Copegus is the Roche brand of ribavirin and was also approved in late 2002. PegIntron (peginterferon a-2b) is made by Schering-Plough. Rebetol is the Schering Plough brand of ribavirin. Study results of these two drugs are available from NATAP (see study results page 19).
Pegylated interferon is an advancement in treating HCV. Pegylated interferon isinjected subcutaneously once per week. It is therefore more convenient & easier totake, and the pegylation process allows for higher and more sustained levels of inter-feron in the human body. The results from recently conducted studies show thatpegylated interferon has superior response rates to standard interferon. Although,the response rates vary by the patient’s genotype and viral load.
These studies found the overall SVR (sustained viral response [<100 copies/ml])ranged from 53% to 61% for pegylated interferon plus ribavirin, compared to about46% for standard interferon plus ribavirin. Individual response varies by genotypeand usually viral load. Patients with genotype 2 or 3 respond well to therapy. Forpatients with genotype 2 or 3, 75%-90% of patients achieved an SVR.
For patients with genotype 1, the response rates in studies of pegylated interferonplus ribavirin were not as good: 53%-74% of patients with low viral load had anSVR. Patients with high viral load and genotype 1 do not generally respond as well:30%-46% achieved an SVR. (see next page for study results). It appears adherenceplays an important role in contributing to succeeding with HCV therapy, as it doesin HIV therapy. Results from 2 preliminary studies found that patients with >80%adherence achieved higher response rates.
PegIntron is a powder that has to be reconstituted with purified water, both of whichcome in separate vials. Pegasys is a liquid that comes in 1 vial and is stored in therefrigerator. PegIntron is dosed by weight. Everyone receives the same dose ofPegasys regardless of weight.
How will coinfected patients respond to HCV therapy? The results of several smallpreliminary studies showed coinfected patients responded as well as HCV monoin-fected patients. However, the interim results of several more recent larger studiessuggest that coinfected patients may not respond quite as well. Some researchers sug-gest that on average the response rates for coinfected patients may be 20-30% less. Again, adherence appears to play an important role. The large studies in coinfectedpatients are ongoing and final results are expected.
In addition to full adherence, there are some things you can do to help improveresponse rates in coinfected patients: starting therapy early in HCV disease, whenCD4 count is higher, and when HCV and HIV viral loads are lower. A healthylifestyle may help: don’t eat too much fat in your diet, as fat can get deposited in yourliver, called fatty liver; exercise; relaxation, good diet (adequate protein; not too muchfast food; eat fresh vegetables and fruit). Drinking alcohol can accelerate progressionof HCV. Study Results Based on 48 Weeks of Therapy & 24 Weeks Follow-up PegIntronTreatment Response in Patients with Genotype 1 PegIntronTreatment Response in Patients with Genotype 2-6 Pegasys Treatment Response in Patients with Genotype 1 Pegasys Treatment Response in Patients with Genotype 2/3
Results from a second large study of Pegasys + ribavirin in HCV monoinfectedpatients were reported in April 2002. The study compared 24 vs. 48 weeks of treat-ment, and also compared 800 mg of ribavirin vs. 1000/1200 mg of ribavirin. Ifpatient weight was less than 165 lbs, they received 1000 mg per day. If patients weregreater than 165 lbs they received 1200 mg of ribavirin per day. The study showeddifferent and better results than those from the first Pegasys + ribavirin study: in par-ticular, patients with genotype 1 and high viral load (> 2 million copies/ml) had bet-ter results. FDA approval for Pegasys is pending and is expected in Fall 2002. 2nd Pegasys + Ribavirin Study – Patients with Genotype 1
Patients with genotype 1 had better results with 48 weeks rather than 24 weeks oftreatment. Patients with genotype 1 had better results with 1000/1200 mg per dayof ribavirin than with 800 mg per day. Most patients in the USA have genotype 1and high viral load. 2nd Pegasys + Ribavirin Study – Patients with Non-1 Genotype
Patients with non-1 genotype had the same results whether or not they had high orlow viral load. Patients who received 24 weeks treatment did as well as patientsreceiving 48 weeks treatment. Patients without cirrhosis had an overall response rateof 65% in this study, while patients with cirrhosis had an overall response rate of50%. The study authors reported that patients with greater than 80% adherence canimprove upon these response rates, and higher ribavirin dosing may be associatedwith more side effects.
Initially after starting HCV therapy, interferon may reduce CD4 cell count, but CD4percentage should not decrease. Usually CD4s bounce back after stopping HCVtherapy. In a few small studies, interferon reduced HIV viral load but the studieswere short term (six months).
It is unclear whether d4T and AZT interact with ribavirin in such a way as to reducethe effectiveness of these AIDS medications. Research in test tubes suggested thatribavirin may have this effect. Preliminary studies in HIV-infected individuals sug-gest this may not be an issue, but we do not have a definite answer to this questionyet. More conclusive studies are ongoing. Test tube studies suggest ribavirin mayincrease the amount of ddI a person is exposed to, which could increase ddI toxici-ty. Several studies have found a few patients taking combination d4T/ddI who afteradding ribavirin and interferon experienced symptoms related to elevated hyperlac-tatemia and mitochondrial toxicity. Patients should be monitored if they add rib-avirin to d4T/ddI. Predictors of the Response to HCV Therapy
• HCV viral load: persons with >2 million do not in general respond as well• Genotype: persons with genotype 1 do not respond as well as individuals with
• Persons with cirrhosis do not respond as well• Women < 40 years of age tend to respond better than men• Excessive alcohol intake worsens HCV progression• Persons with lower weight tend to respond better to therapy• Better adherence improves response• Excess of fat in your diet can be harmful to the liver
Managing Side Effects of HCV Therapy
Therapy can be difficult to tolerate but there are things you can do to make sideeffects more tolerable. Tylenol or Advil can be helpful, but over 2000 mg per day ofTylenol can be toxic to the liver. Vioxx and non-steroidal anti-inflammatory drugscan reduce aches & pains. Make sure to discuss with your doctor which of thesetypes of medications are appropriate for you, and how to dose them. Maintainingregular physical and mental activity can help cope with fatigue & depression. Lightwalking and physical activity may help. Do not overdo exercise. It’s important tonap or rest when you feel tired, but remaining sedentary will not help with fatigueand depression.
If you are having trouble with depression, anxiety, and irritability, tell your doctor. Prescribing an anti-depressant can be helpful. Remain well hydrated by drinking and
plenty of fluids. Some individuals lose weight because they do not eat well. Thiscould be due to loss of appetite while taking HCV therapy or to experiencing GI sideeffects (nausea, diarrhea). Eating small, frequent snacks or meals throughout the dayrather than infrequent large meals may be easier to tolerate and may sustain you bet-ter. Not eating properly can increase fatigue and this can increase depression. HCVtherapy can reduce your ability to think clearly and may impair your motor skills. Adequate rest and relaxation may help. Remember HCV therapy is only for up to 12months. By reminding yourself it will end in one year and is time-limited, this mayhelp you stick it out. It may be helpful to share with people close to you or peopleyou live with information about these potential side effects. Ask them to read aboutit in this handbook. When to Begin HCV and HIV Therapy: HAART and HCV
Consult with a knowledgeable doctor about whether or not you should begin HCVor HIV therapy first. You should weigh the pros and cons about which treatment tobegin first. It may be appropriate for you to treat HCV first. There is no consensuson when to begin therapy, but there is information that can help you decide whetherto start HCV treatment early or to delay it
HIV medications can be burdensome to the liver: Opinions are mixed about whetherHIV medications have a negative impact on HCV disease.
• Use of some HIV drugs can result in elevated liver enzymes, which are often just
mild elevations. Liver enzymes should be closely monitored, particularly afterstarting HAART. Persons co-infected with HIV and hepatitis C or B are morelikely to have elevated liver enzymes. The significance of elevated liver enzymesare not understood yet.
• Elevated levels of fats (cholesterol, tryglicerides) can result from HIV drugs and
• Certain NRTIs (for example, AZT, d4T) can cause mitochondrial toxicity to cells,
and this may be harmful to cells in the liver.
• HCV infected patients may develop elevated glucose and reduced bone mineral
• HCV coinfected patients may be more likely to develop lipodystrophy (body
changes) elevated cholesterol, triglycerides, and glucose or insulin resistance, per-haps due to liver impairment.haps due to liver impairment.
• There is little research into the question of the effect of HIV medications on a
• There is little research into the question of the effect of HIV medications on a
• Treating HCV before treating HIV may be beneficial because it might help the
liver tolerate the HIV drugs better.
• If liver toxicity occurs after starting HAART, options include continuing current
regimen with close monitoring, changing HIV drugs, and treating HCV.
Bear in mind that not treating HIV can have severe consequences. Since HIV canprogress more rapidly than HCV, it may be preferable to treat HIV first. HIV ther-apy improves the immune system, which can result in a temporary flare up of ALT(liver enzymes) within the first 5 months after starting HIV therapy. These flare-upsusually settle down on their own, but can also be controlled by changing or inter-rupting therapy.
Each individual is different and treatment decisions should be determined on anindividual basis. A comprehensive and informed discussion with a specialist aboutthe concerns listed here is recommended.
Starting HCV therapy early in the disease stage may present a better opportunity toachieve undetectable HCV viral load or a Sustained Virologic Response. Responseto HCV treatment may be better in early disease, due in part to perhaps less muta-tions and damage to the liver having occurred, and because the person's immune sys-tem may be able to be more responsive to the virus and to treatment.
Once a person has cirrhosis, they may be less likely to achieve a Sustained VirologicResponse to therapy. When CD4s are high, such as over 500, this may be the bestopportunity to achieve undetectable HCV viral load and a Sustained VirologicResponse (SVR). If CD4s decline too low, the ability to achieve undetectable HCVviral load may be lessened. We do not know what is too low of a CD4 count, butpossibly 200 CD4s.
Given an individual's personal situation, it may be more important to get HIV undercontrol, and therefore, to treat HIV first. This may be based on the person's HIVviral load, CD4 count, and health status. Some doctors will decide that if HIV viralload is greater than 40,000 copies/ml, treatment for HIV should start first. But,opinions by doctors may be mixed. A CD4 count of 500 or more before decliningmay be more helpful in response to HCV therapy and the immune response to HCVthan an increase in CD4 count to 500 after starting HIV therapy. But this is notestablished.
Additional factors to consider in deciding whether to defer HCV treatment include:readiness to begin and complete therapy, difficulty in tolerating interferon and rib-avirin, low response rates, more tolerable and effective treatments may be availablein several years. Bear in mind that HIV may accelerate HCV progression. Therefore,if treatment is deferred, close monitoring of the liver condition may be crucial.
Among people with HCV alone, some individuals may not get sick from HCV, but we do not know if this is also true for persons with co-infection. What is Maintenance Therapy?
If a patient does not achieve a Sustained Virologic Response (SVR) and hasadvanced liver disease, continuing on interferon rather than stopping therapy iscalled Maintenance Therapy. Frequently, the maintenance therapy regimen will con-sist only of a reduced dose of interferon (for example, half-dose of pegylated inter-feron). At times, they may use a full dose of interferon. Some doctors add ribavirinto a reduced interferon dose. Maintenance therapy may be an important alternativeif a person cannot achieve an SVR and may have advanced liver disease. Reasons formaintenance therapy follow:
A number of studies suggest that interferon can improve the condition of the liver(fibrosis and inflammation) even when it has no effect on HCV viral load. Continuing on a maintenance therapy regimen of interferon may be able to maintainthat improvement.
Results from several studies suggest that interferon may reduce the risk of pro-gression to liver cancer and severe liver disease (decompensated cirrhosis), evenwhen there is no sustained reduction in viral load and no normalization of ALT. Also, interferon may reduce ALT without a virologic response.
It is believed that interferon may have a preventive effect that is not related to ananti-viral effect. It may have an anti-fibrotic effect and effect the immune response,which could slow or stop progression of fibrosis & inflammation.
The decision to continue or maintain therapy should take into consideration the per-son's ability to tolerate treatment and the risk of HCV progression (if the patient hasa high degree of inflammation and fibrosis, maintenance therapy may be moreimportant to slowing their disease progression, so they do not pr ogress to a seriouscondition). Treatment Effect of Maintenance Therapy As discussed earlier, the response rate is lower for people with genotype 1, and in general with viral loads above 2 million, or with early cirrhosis. Response rates are higher for individuals with genotype 2 or 3. Unfortunately, most co-infected per- sons and most people in the US have genotype 1. If a person has had HCV for many years they may have advanced liver disease. Achieving an SVR is less likely in the circumstances described above.
As mentioned above, studies show that even if a person cannot achieve a SVR, thecondition of the liver may have improved and progression of fibrosis may be slowedor stopped. If such an individual stops therapy, the improved liver condition(referred to as improved histology) may fade over time. Research studies suggestthat keeping a person on maintenance therapy may sustain that improvement. Bearin mind, there is no consensus that maintenance therapy will be successful in slow-ing or stopping progression. Two large studies are ongoing to look at this, but studyresults may not be available for several years. Maintenance therapy may be the onlyoption for some persons with advanced liver disease. New Goal for HCV Treatment In many ways, HCV is at the same point as HIV was 10 years ago. There is currently only one treatment for HCV: interferon and ribavirin. Ten years ago only AZT was available to treat HIV. So, the goal ten years ago was to stay alive long enough and remain relatively healthy until new treatments could be developed. This applies to HCV now. If a person cannot reduce their HCV viral load to undetectable or achieve a Sustained Virologic Response, a secondary goal is to improve the condi- tion (inflammation and fibrosis) of the liver enough so that a person can be alive and healthy enough for treatments now in development. As discussed above, that is the goal of maintenance therapy -- to delay or prevent HCV progression. New HCV Drug Research Research into new drugs for HCV is receiving much attention. Many new potential treatment directions and drug candidates are being explored. Various types of anti- viral and immune therapies are in early research. A few new potential treatments have just started in human studies. It is expected that a number of new treatments will be developed and available, but not for several years. Promising potential drug developments include protease inhibitors for HCV, helicase inhibitors, polymerase inhibitors, maximine (immune-based therapy), ribozymes, and antisense molecules. Drugs that slow or stop fibrosis are being researched. In November 2002, initial results were reported from a small study of the first HCV protease inhibitor. Patients with chronic HCV received the drug for 48 hours and saw potent 2-3 log reductions in HCV viral load, and so far there were no safety concerns observed. Follow-up studies are expected to begin in early 2003. Vaccine Development There are a number of research efforts in trying to find a vaccine--both for preven- tion and therapeutic. But the possibility of finding a vaccine for HCV has similar difficulties to the problem of finding a vaccine for HIV. The high mutation rates and the genetic diversity of these viruses, make it difficult to find a vaccine to con- quer them. Diet, Herbs and Vitamins If a person has cirrhosis they should avoid raw clams, mussels and oysters, and iron and vitamin A supplements (which can accumulate in the liver).
Some doctors or nutritionists may suggest unusual diets for people with HCV, suchas a meat-free diet. Many doctors do not feel there is evidence that such a diet ishelpful unless a person has serious complications of liver disease. It is generallyaccepted that a diet with adequate amounts of fresh vegetables and fruits should befollowed. Try to eat an overall healthy and balanced diet. Moderate exercise shouldbe helpful. For the person with HIV, a meat free diet may be harmful. Herbs: There are several concerns about using herbs. There is little evidence that herbs can help with HCV. In fact, some herbs have been identified as being harmful to the liver. Herbal products are not regulated by the FDA. There is no inspection or mon- itoring for safety of ingredients and the uniformity of the amount of active ingredi- ents. This means that one capsule or a portion of raw herbs could have more active ingredients than another could. Another concern is that an herbal product can have an interaction with HIV drugs. For example, one herb has been studied by the National Institutes of Health -- St. John's Wort. NIH researchers found that this herb severely reduced blood levels of the HIV protease inhibitor Crixivan. As a result, the FDA has issued a recommendation to doctors that St. John's Wort should not be used with protease inhibitors or NNRTIs, also used to treat HIV. Preliminary research at the NIH found that Milk Thistle did not appear to affect indinavir levels. Further research is expected to confirm this. Vitamins: It is generally accepted that if a person with HCV takes a multiple vitamin, it should be iron-free. You can see iron-free on the front of the bottle. Additional Alternative Approaches: Stress reduction may be helpful. Various techniques which can be used include: yoga, exercise, meditation and relaxation techniques, massage therapy, and acupunc- ture. Before starting an exercise regimen, please consult with your doctor. National AIDS Treatment Advocacy Project NATAP Programs:
-- NATAP Reports newsletter-- NATAP Web Site www.natap.org-- Community Treatment Education Program: on site at over
-- HIV and Hepatitis Treatment Education Series Forums at
-- Email Treatment & Conference Updates-- All programs and materials available in English and Spanish
NATAP National Hepatitis C and HCV/HIV Co-infection Training Institute
This program provides treatment education on HCV and HIV toorganizations and community in any city throughout the USA. If youwould like NATAP to visit your site or provide educational programs inyour city, please call 1-888-26-NATAP.
NATAP580 Broadway, Suite 1010New York, NY 10012Tel: (212) 219-0106Fax: (212) 219-8473Email: email@example.com
Free copies of this handbook are available from NATAP. National AIDS Treatment Advocacy Project 580 Broadway, Suite 1010 New York, NY 10012 Tel: (212) 219-0106 Fax: (212) 219-8473 Email: firstname.lastname@example.org Treatment Website: www.natap.org
Printing supported by a grant provided by Roche.
FURTHER REVELATIONS by C.Lovell. INTRODUCTION. Most of the information in this paper has not been easy to obtain, and much of it is sensitive. In most casesthe sources of information have been indicated by a code; refer to the last sheet for the bibliography andcodes. All statements have been made in good faith, but it is possible that some of the reference books arenow out of date, or that
Understanding Indigestion and Ulcers Professor C.J. Hawkey and Dr N.J.D. WightPublished by Family Doctor Publications Limitedin association with the British Medical Association IMPORTANT This book is intended not as a substitute for personalmedical advice but as a supplement to that advice for the patient who wishes to understand more about his In particular (without limit) you should no