Surviving Hepatitis C in AZ Jails, State Prisons, and Federal Detention Centers.

Surviving Hepatitis C in AZ Jails, State Prisons, and Federal Detention Centers.
The "Hard Time" blogspot is a volunteer-run site for the political organization of people with Hepatitis C behind and beyond prison walls, their loved ones, and whomever cares to join us. We are neither legal nor medical professionals. Some of us may organize for support, but this site is primarily dedicated to education and activism; we are fighting for prevention, detection, treatment, and a cure for Hepatitis C, particularly down in the trenches where most people are dying - in prison or on the street... Join us.


Tuesday, November 23, 2010

Mental illness in Arizona's state prisons: Chuck Ryan on the carpet, again.

The following is a cross post from Arizona Prison Watch and the Prison Abolitionist blogs, to give those of you who have been following the concerns about Hep C in Arizona's Department of Corrections' facilities some context.

Sorry for the redundancy, my Facebook friends who are already getting feed, and those of you picking up my other tweets.

To those of you for whom this is all news, follow the links for more background.


The following was posted to another site on Friday, November 19, 2010 by the former AZ Department of Corrections deputy warden who was interviewed by Channel 12 this summer and called for Chuck Ryan to resign. It's being reprinted here with Carl's permission. 

As some of you may know, one of the corrections' officers unions also called on the governor to fire Ryan in a letter of no confidence two weeks ago. I shouldn't have to point this out, but prisoners aren't the only ones behind bars at heightened risk under current conditions. The front line staff also have good reason to be concerned.

Needless to say, none of us are making friends in Arizona's high places. In fact, since the people we're antagonizing have badges and guns on their side - as well as the keys to the prisons - it would help if the public and media really watch our backs out here.

Other witnesses to the institutionalized neglect and abuse of prisoners with mental illness in Arizona are urged to contact the US Department of Justice's Civil Rights Division; send them what you know and request that they initiate a CRIPA investigation before the next ADC suicide or homicide goes down. If you need to you may remain anonymous while doing so.


Friday, November 19, 2010

Arizona: Mercy, Mercy Me...

Davon's clemency board hearing was yesterday - the decision to turn him down was clearly made before we walked into the room, however. The chair made only passing reference to the thick stack of mail that had arrived in support of Davon's application, and cut me off when I was speaking on his behalf. He made a special point of reading things into the record to justify their determination against him. The county attorney's office can be expected to oppose such applications, but they went out of their way, it seems, to damn him - which was precisely what the board needed and asked for. Not that I'm accusing them of any impropriety - I'm sure they did what they felt was right - just as I'm doing. We just come from different places, and they don't know Davon like I do. As evidenced by their decision yesterday, They don't know him at all.

Pardons in Arizona have nothing to do with mercy or grace, by the way - or even justice for that matter, even when sincere people try to deliver it. Look at what our good governor did to Bill Macumber, the innocent man who has already spent 35 years in prison for murder and may well die there. Convinced beyond any doubt that his conviction was based on perjured testimony and manufactured evidence, the Arizona Board of Executive Clemency unanimously recommended him for a full pardon, which would have gone into effect if Brewer had simply left it alone for 90 days. Instead she quashed it, in the interest of her kind of "justice". Affirming Bill's innocence would have implied his ex-wife's guilt. As she worked for the Maricopa County Sheriff's office at the time she framed him, I suspect Brewer was doing someone with history there a favor. But what do I know?

Sadly, despite his story saturating the media across the country before November 2, the voters in Arizona elected that woman anyway.

As for Davon: the outcome of his hearing was no surprise, really - probably least of all to him - but it was still a disappointment; his little sister left the room abruptly in tears. We did, however, raise awareness about the prosecution of the seriously, mentally ill for their symptoms rather than their criminality, and built a network for prisoners with Hep C and their families. We also entered our objections to the prison industrial complex into the public record (that was the part I think they didn't want to hear). One of our legislators even turned out to corroborate Davon's mom's assertion that Arizona's prisoners aren't getting the medical care they need in there - and that came from a self-described "conservative Republican". I suspect he will pay a price for having done that, which is why I won't name him here. I doubt he would endorse my own take on the system, but he's still one of the few politicians I've ever met with real integrity. I can't think of a single Democrat in this state who would put themselves on the line like that for a convicted violent, crazed felon seeking mercy - much less another Republican.

I'm convinced that clemency boards exist largely to reinforce the illusion that the system we have of doling out punishment in our country is a "just" one that serves the best interests of society at large. By allowing room for pardons and commutations, we suggest that the legal system we live under, as a rule, delivers justice to criminals and victims alike, and that any abuse of power or injustice perpetrated by the state in the process is an exception that needs to be dealt with on a case-by-case basis. If that was the reality, however, our prisons would not be packed almost exclusively with the poor - most of whom have the least ability to do great harm. In a truly just and morally evolved society it is the money-lenders, warmongers and rogue sheriffs of this land who would be doing time for exploitation, mass murder, and kidnapping - not making the rules the rest of us have to live by. They certainly wouldn't be retiring with honors and drawing down our collective dime.

But ours is neither a just nor a moral society - it isn't even a democracy. It is a capitalist republic in which the wealth and power of the few still depends on their ability to co-opt, terrorize, and restrain the many. We literally replaced our plantations with prisons when overt slavery went out of style. America's governments exploit and injure far more innocent and vulnerable people than all our lone criminals combined do. We've even made the perpetuation of victimization and crime an attractive, acceptable industry from which savvy investors can profit.

Thanks, everyone, for all your support through this. Stay with us, please - this fight is much bigger than one young man, and has only just begun. Keep an eye on what's happening with Davon for awhile longer - he went further out on a limb in the interest of prisoner rights and health care than any of the rest of us had to - and risks paying a much higher price now than the one extracted from him at sentencing. We'll see if he's allowed to keep his good time - and make it successfully through the 4 years of probation he has yet to serve -in light of his and his mother's public defiance. I guess we'll also see if the Arizona State Legislature shows any mercy for the honesty and courage of one of their own.

Thursday, November 18, 2010

Hep C treatment: Prison and Beyond.

Why isn't this being done in Arizona?


New York State Hepatitis C Continuity Program Fact Sheet

Download a printable version of this Fact Sheet (PDF, 397 KB, 1pg.)

What is the Hepatitis C Continuity Program?

The Hepatitis C Continuity Program is a program for New York State (NYS) Department of Correctional Services (DOCS) inmates who are under treatment for hepatitis C (HCV). The program promotes treatment completion upon and after release to the community.

This Program makes it possible for treatment to be initiated in DOCS regardless of the incarceration time remaining, since arrangements for continuity of treatment after release are possible. It enables inmates who initiate treatment prior to release to receive timely referral to appropriate community-based health care providers for continuation of treatment.

How does the Program work?

Participation on the part of inmates is voluntary and there is no cost to the inmate while incarcerated or after release. DOCS Health Services staff and facility Parole Officers work with inmates prior to initiation of treatment to:
  • Arrange participation;
  • Secure appropriate Release of Information forms;
  • Arrange for Medicaid eligibility; and,
  • Select a health care provider for referral for treatment completion in the community.

How do health care providers participate?

As release approaches, an initial medical appointment is made with the participating health care provider. Providers accept referrals for administration of medication. This involves a single staff person who receives the patient's signed Release of Information forms and full medical record from the DOCS facility.

How are medications obtained?

DOCS staff arrange for shipment to the receiving health care provider of a two-week supply of Pegylated Interferon and Ribavirin, or similar medications, for use with the releasee while Medicaid, other coverage or participation in patient assistance programs is being arranged.

How many patients should the health care provider expect for treatment?

Only a small volume of patients are referred to each health care provider. To increase the probability of success, patients receive a thorough program orientation before release. As appropriate, Parole Officers are an additional resource to help secure arrangements to increase the probability of appointments being kept. For example, Parole Officers may provide access to supportive services (e.g., mental health, housing, substance use treatment), given the severe side effects that many patients experience while being treated for HCV. Taking these steps will increase the probability of successful treatment outcomes.

The Hepatitis C Continuity Program is a partnership between the NYS Department of Correctional Services, NYS Department of Health, NYS Division of Parole, NYC Health and Hospitals Corporation and other community-based health care providers. For questions regarding the Hepatitis C Continuity Program, please contact:

Colleen Flanigan, Hepatitis C Coordinator
NYS Department of Health
(518) 486-6806

Early Treatment for HCV: New York State of Mind

Clinical Guidelines for the Medical Management of Hepatitis C

New York State Department of Health

E. Treatment of Hepatitis C

The primary goal of HCV therapy is to achieve a SVR, defined as an undetectable HCV RNA 6 months after stopping antiviral therapy. Secondary goals of antiviral therapy include improvements in histology, quality of life and prevention of hepatocellular carcinoma. Antiviral therapy is approved by the Food and Drug Administration (FDA) for patients with persistently abnormal liver enzymes, detectable HCV RNA and an abnormal liver biopsy. Recent data have shown that patients with normal liver enzymes, detectable HCV RNA and an abnormal liver biopsy respond to therapy at similar rates as those with abnormal liver enzymes.55

The efficacy of HCV treatment has improved over the past decade. Initial treatment consisting of interferon alpha has been replaced by pegylated interferon and now by combination therapy using pegylated interferon and ribavirin. Efficacy varies depending on multiple factors especially viral genotype, but achieving sustained viral suppression in 50% of patients can be expected.

1. Patient Evaluation and Treatment


Treatment should be considered for all patients with detectable HCV RNA and an abnormal liver biopsy, regardless of the presence or absence of liver enzyme elevation.

Prior to making a decision regarding treatment, patients should be evaluated with HCV RNA, HCV genotype, liver enzymes (ALT), and liver biopsy, unless contraindicated. The decision to initiate antiviral therapy should be made based upon the willingness of the patient to undergo therapy, ability to regularly attend appointments, and agreement to use contraception to prevent pregnancy. The decision to initiate antiviral therapy should be made on an individualized basis that considers severity of liver disease, co-morbid conditions, the potential for serious side effects and the likelihood of response.

Patients with HCV infection on methadone maintenance therapy should not be considered ineligible for treatment.

The treatment of the actively using injection drug user is not contraindicated and may be appropriate under some circumstances. Patients with a history of well-controlled psychiatric disorders may be excellent candidates for antiviral therapy and should be under the care of a qualified mental health professional.

Treatment of HIV/HCV co-infected patients should be offered with pegylated interferon and ribavirin, unless contraindicated. Patients co-infected with HIV/HCV should be managed by experts in both viruses. The basic tenets of HCV management should not change, but the provider must be prepared for possible hepatotoxicity and drug-drug interactions. Further recommendations for the HIV/HCV co-infected patient are provided at: CRITERIA FOR THE MEDICAL CARE OF ADULTS WITH HIV INFECTION

All patients with CHC infection are candidates for antiviral therapy. These patients are defined by detectable serum HCV RNA and an abnormal liver biopsy consistent with chronic liver disease. Treatment is recommended for patients with significant inflammation or fibrosis.23

There are relatively few contraindications to antiviral therapy although the decision to initiate therapy should be made after ensuring that the patient understands the risks and benefits of pegylated interferon and ribavirin. Current absolute contraindications to combination therapy include a known hypersensitivity to pegylated interferon and/or ribavirin, autoimmune hepatitis, decompensated liver disease, pregnant women, men whose female partners are pregnant and patients with hemoglobinopathies.56,57 Many patients with hepatitis C will also have underlying mental illness such as depression. Uncontrolled psychiatric illness and suicidal ideations or attempts are contraindications to antiviral therapy. Patients with remote histories of suicidal ideation or attempt warrant further evaluation to assess suitability for treatment. On the other hand, patients whose psychiatric disorders are under control and who are regularly followed by mental health providers are often excellent candidates for antiviral therapy.

IDU is the most common mode for acquisition of HCV infection. Patients with a history of injection drug use who are no longer using recreational injection drugs are treated in the guidelines as noted above. Methadone use has not been shown to adversely affect SVR rates or interfere with patient adherence to medication regimens. Patients enrolled in methadone maintenance programs should be considered for antiviral therapy.58

The treatment of actively injecting drug users is controversial and raises concerns related to adherence to therapy and the potential for re-infection. Patients actively using injection drugs should be offered drug counseling and psychiatric support services. Like all patients, treatment of the actively injecting drug using person should be based upon the willingness of the patient to undergo therapy, ability to regularly attend appointments for close monitoring, and agreement to use of contraception to prevent pregnancy.

2. Environmental Assessment and Support

Environmental support is an important part of patient assessment because treatment may be given for up to one year, and the adverse effects of treatment may incapacitate patients. A patient's living situation and household income should be addressed prior to treating treatment. Homelessness may be a significant problem, and the need for a support network for such patients should be assessed and arranged before the treatment. In addition, most formulations of pegylated interferon now require refrigeration. Family meetings can be helpful to prepare family members for side effects of treatment. Neuro-psychiatric side effects such as irritability and hostility can strain relationships if unexpected. These issues can be assessed with the collaboration of social services. Family and friends may need to help with activities of daily living including transportation to medical appointments. Home health nurses and case managers may be helpful in providing support at home.

3. Initiating Treatment


Prior to treatment, patients should have a baseline complete blood count (CBC), chemistry evaluations, serum creatinine, thyroid function tests, pregnancy tests in women, HIV testing, contraceptive counseling for men and women, and screening for depression.

Prior to initiating treatment, patients should be informed of the possible side effects of therapy to allow them to anticipate and manage with these side effects.

The treatment of choice for patients with chronic hepatitis C infection is combination pegylated interferon and ribavirin. Patients infected with genotype 1 or 4 should be treated for 48 weeks with combination pegylated interferon and ribavirin. The ribavirin dose should be 1000 mg a day in patients <75 kg and 1200 mg a day in patients >75 kg.

Patients infected with genotype 2 or 3 should be treated for 24 weeks with combination pegylated interferon and ribavirin. The ribavirin dose should be 800 mg a day.

Several treatments are licensed in the U.S. for the treatment of CHC. These agents include interferon alpha-2a, interferon alpha-2b, interferon alpha con-1, and interferon alpha-2b in combination with ribavirin; pegylated interferon alpha-2b alone and in combination with ribavirin; and interferon alpha-2b and pegylated interferon alpha-2a alone and in combination with ribavirin. Data from multiple clinical trials clearly supports the use of pegylated interferon in combination with ribavirin.

Pegylated interferon has been a major advance in the treatment of CHC. The concept behind the pegylation of interferon is to produce a molecule which maintains longer lasting therapeutic concentrations by optimizing both absorption and distribution while decreasing the rate of clearance and deceasing proteolysis. This is accomplished by the addition of a polyethylene glycol molecule [PEG] to standard interferon by way of a covalent bond. This PEG molecule is non-toxic polymer that is readily excreted in the urine. The PEG molecule can be either linear or branched. Larger PEG molecules produce greater reductions in renal clearance and provide more subcutaneous absorption.

Two pegylated molecules are currently being used in the U.S. Pegylated interferon alfa-2b (Peg-Intron; Schering-Plough) is a linear 12 KD molecule, and pegylated interferon alfa-2a (Pegasys; Roche) is a 40KD branched chain molecule. These products are both manufactured using recombinant DNA technology in an Escherichia coli system. Both products have dose related maximum concentrations. Pegylated interferon alfa-2a is given as a fixed dose whereas pegylated interferon alfa-2b is dosed according to patient weight.

One study compared once weekly pegylated interferon alfa-2a with standard interferon alfa-2a three times a week for 48 weeks in previously untreated patients with hepatitis C.59 The SVR rate in the pegylated interferon group was 39% compared to a 19% response rate in the standard interferon group. The SVR rate of genotype 1 patients receiving peginterferon alfa-2a was 28%. The frequency and severity of adverse events was similar in both groups. Pretreatment factors that were associated with a sustained virologic response in this study, in order of significance, include genotype other than type 1, ALT quotient greater than three, HCV RNA level less than two million copies (Cobas Amplicor HCV-PCR version 2; Roche), body surface area less than 2 meters, lack of bridging fibrosis or cirrhosis, and age less than 40 years. Side effects were less with the group treated with pegylated interferon alfa-2a than the group that received standard interferon therapy.

The highest SVR rates in previously untreated patients with chronic hepatitis C have been reported with combination pegylated interferon and ribavirin. In one study of 1530 patients, a 54% SVR was reported in patients treated with pegylated interferon alfa-2b plus ribavirin.60 This was compared to a 47% SVR rate in patients treated with three times a week standard interferon plus ribavirin. The response rates to pegylated interferon alfa-2b plus ribavirin for genotypes 1 and non-1 were 42% and 82%, respectively.2 In a retrospective analysis of the data, the authors report that patients receiving more than 10.6 mg/kg of ribavirin had higher sustained response rates, regardless of treatment group. Another study showed that patients with genotypes other than type 1, regardless of ribavirin dose and treatment duration, had a sustained reponse of 80%, leading to the recommendation that non-type 1 patients can use a ribavirin dose of only 800 mg and can discontinue treatment after 24 weeks.61

Side effects between the groups receiving pegylated interferon alfa-2b and standard interferon were similar although there was significantly more fever, weight loss, nausea and injection site reactions in the group receiving pegylated interferon alfa-2b. Several studies have documented a decreased sustained viral response rates in African-American patients infected with hepatitis C when compared to Caucasians and Asian-Americans. One prospective study evaluating the SVR rates of African-Americans and whites receiving pegylated interferon alfa-2a plus ribavirin for 48 weeks, reported a response of 26% for blacks compared to 39% for whites.62

4. Monitoring While on Treatment


Patients who do not achieve virologic suppression or a 2-log decrease in HCV RNA at 12 weeks may have therapy discontinued, although factors such as degree of fibrosis and tolerability of therapy should be considered.

Patients should have a CBC and chemistry evaluations 2 weeks after initiation of treatment to assess for potential toxicities. CBC, chemistry evaluations, and pregnancy tests in women should be done routinely at each follow-up visit and not less often then every 4-6 weeks during treatment.

Patients who achieve an end-of-treatment virological response should have HCV RNA testing performed 24 weeks after stopping treatment to evaluate for a SVR.

Erythropoetin alfa and granulocyte colony stimulating factor (G-CSF) may be used to treat anemia and neutropenia, respectively, in order to maintain the patient on full medication doses.

Providers should reference the full discussion of side effects of hepatitis C treatment in Appendix A.

One analysis of pegylated interferon alfa-2b plus ribavirin showed that genotype 1 patients who did not achieve either viral eradication or a drop in baseline HCV RNA by more than 2 log at 12 weeks of therapy had <1% chance of achieving a SVR. Patients who do not achieve this "early viral response" can have therapy discontinued. This action is both cost effective and can improve patient quality of life.63 The key factor in achieving a sustained viral response with pegylated interferon and ribavirin appears to be the patient's ability to adhere to the treatment regimen. Adherence is directly related to side effects and tolerability. Better understanding of the toxicities and side effects of combination therapies and their management should lead to better outcomes. Common side effects of pegylated interferon plus ribavirin therapy include the development of flu-like symptoms, fatigue, alopecia, rash, cough, insomnia, anorexia, thyroid disease, injection-site reactions, vision disorders, anemia, neutropenia, and thrombocytopenia. Rarely, colitis, pancreatitis, and severe pulmonary disease have been observed on alfa-interferon and ribavirin therapy.56,57

Ribavirin may cause birth defects and/or death to the exposed fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients taking pegylated interferon plus ribavirin. Ribavirin therapy should not be started unless a report of a negative pregnancy test has been obtained immediately prior to initiation of therapy. Women of child-bearing potential and men must use two forms of effective contraception during treatment and for at least six months after treatment has concluded. Monthly pregnancy tests must be performed routinely throughout the treatment and follow-up phases.64

Pegylated interferon and ribavirin have been found to be safe and effective in HCV mono-infection and in co-infection with HIV.2,61 Safety and efficacy has not been established in patients who have received liver or other organ transplants, in patients who have failed other alpha interferon treatments and in patients under the age of 18.56,57

Neutropenia is commonly seen with pegylated interferon alfa-2b, and 18% of those receiving pegylated interferon at 1.5 ug/kg required a dose reduction due to significant neutropenia. Anemia secondary to ribavirin was also common. Ribavirin dose reduction was seen in 9% of patients treated with pegylated interferon 1.5 ug/kg in combination with 800 mg of ribavirin, and in 13% of those treated with standard interferon and 1000-1200 mg of ribavirin.

5. Re-treatment of Patients Previously Treated for Hepatitis C


Re-treatment of inadequately treated patients is recommended with a combination of pegylated interferon and ribavirin.

Re-treatment of non-responders or relapsers to antiviral therapies other than a combination of pegylated interferon and ribavirin should be strongly considered.
Re-treatment of Patients Who Failed to Respond to Previous Therapies
A large segment of patients with hepatitis C fall into the category of those who did not respond previous to therapy. A careful history must be obtained in these patients to determine if re-treatment should be considered. Patients who did not respond to therapy fall into three general categories: (1) those who were inadequately or inappropriately treated initially, (2) non-responders and (3) relapsers. In addition, patients may fit into any of these three categories after treatments with interferon monotherapy, three-times-weekly interferon plus ribavirin, or pegylated interferon plus ribavirin.
Re-treatment of Inadequately or Inappropriately Treated Patients
Inadequately treated patients are those who either received less than the recommended doses of interferon or ribavirin or were treated for a shorter duration of therapy to make an appropriate assessment as to their response. It is important that all treated patients are encouraged to remain on the baseline dosages of interferon or ribavirin unless untoward effects necessitate dose reduction for a minimum of 12 weeks in order for an assessment of early viral response to be obtained. Inadequately treated patients should be considered for re-treatment with pegylated interferon and ribavirin if no contraindications are noted.
Re-treatment of Non-responders
In patients previously treated with interferon monotherapy, approximately 25-40% may achieve a SVR when treated with pegylated interferon and ribavirin.66,67 Approximately 10% of patients who did not respond to three-times-weekly interferon plus ribavirin will have a SVR with pegylated interferon and ribavirin. Factors associated with a response to retreatment include non-genotype 1 infection, lower baseline HCV RNA levels, less fibrosis on liver biopsy and non-African-American race.66,67 There currently are no published data on the re-treatment of patients who fail to respond to treatment with pegylated interferon and ribavirin.
Re-treatment of Relapsers
Relapse is defined as the reappearance of serum HCV RNA in a patient with previously undetectable HCV RNA at the end of antiviral therapy. Relapse following interferon monotherapy is more common than relapse following combination interferon and ribavirin therapy or combination pegylated interferon and ribavirin therapy.

Large studies show that often relapsers following monotherapy with interferon alone respond favorably to standard interferon plus ribavirin. It seems reasonable to presume that such relapsers will respond to combination pegylated interferon plus ribavirin. The growing problem facing physicians today is how to approach the patient who relapses following combination interferon plus ribavirin or combination pegylated interferon plus ribavirin therapy. Unfortunately, there are limited data currently available to address this issue.

6. Treatment of HCV-Infected Children

Diagnostic evaluation for the presence and severity of HCV infection, including liver biopsy, should be performed in children as in adults.

Therapy with standard interferon and ribavirin may be offered to children aged 3-17 years if given under the care of experienced physicians.

Antiviral therapy should not be administered to children under the age of three.

Children infected with HCV are less likely to manifest symptoms and are more likely to have normal or minimally abnormal liver tests compared with adults. They generally have a slower rate of progression to advanced liver disease. However, there are multiple factors that support treatment of HCV infection in children. These factors include the anticipated long duration of infection after early acquisition, relatively good tolerance of antiviral medications, and avoidance of social stigmatization. Nevertheless, careful selection of appropriate candidates for therapy is important. If a contraindication to current therapeutic agents is present, treatment should be withheld until this has resolved or until new agents are available. Children without contraindications to the medications used for hepatitis C should undergo liver biopsy to determine the presence and degree of fibrosis. In the absence of fibrosis, treatment may be deferred. If any degree of hepatic fibrosis is present, antiviral therapy for HCV should be considered. At present, in the U.S., the only therapy approved for children by the FDA is a combination of interferon alfa-2b and ribavirin. The results of several studies using interferon monotherapy or combination therapy with standard interferon and ribavirin indicate that SVR rates are as good or better than those achieved in adults. Children generally tolerate interferon therapy better than adults; in small numbers of children reported so far dose-dependent hemolytic anemia has been less severe than in adults.68 Although safety data have not yet been developed, pegylated interferon in combination with ribavirin offers improved efficacy and should be considered in adolescents older than 16 years of age who are post-pubertal, or in younger children in the context of clinical trials. Multicenter trials are currently underway to determine the safety and effectiveness of other forms of therapy for HCV infection in children.68 The safety and pharmacokinetics of hepatitis C therapies have not been determined for children younger than 3 years of age.

7. Treatment of Individuals with Acute Hepatitis C Infection

Although there are no controlled trials recommending treatment of acute HCV infection, the use of pegylated interferon monotherapy may prevent the development of CHC infection, although the duration of therapy in still unknown.

There are insufficient data to recommend the use of ribavirin in the acute setting.

Therapy should be deferred until 12 weeks after exposure, to allow for spontaneous clearance to occur, thus avoiding therapy.

The acute phase of HCV infection is seen as a window of opportunity during which the establishment of chronic hepatitis C and its associated morbidity may be prevented.22 A meta-analysis of trials of various interferon alfa monotherapy regimens showed an average SVR rate of 42%, although the quality of these trials was variable.69

Acute HCV infection is seldom seen in clinical practice. Therefore, there is a paucity of well-designed, randomized controlled trials for the treatment of this patient.70 One study reported that intensive treatment of acute hepatitis C with interferon alfa-2b resulted in a 98% SVR. Although there is no standard therapy for the treatment of acute hepatitis C, this study strongly suggests that treatment with interferon monotherapy at higher than standard doses is highly effective in eradicating acute infection.71 Two more recent studies have reported on the effectiveness of pegylated interferon monotherapy for acute hepatitis C.72,73 These studies support initiating therapy after an initial waiting period of approximately 12 weeks after exposure to allow for spontaneous clearance to occur, thus avoiding therapy altogether.

CDC: Early HCV treatment saves lives, money.

Evaluation of Acute Hepatitis C Infection Surveillance --- United States, 2008

Centers for Disease Control: Morbidity and Mortality Weekly Report (MMWR)

November 5, 2010 / 59(43); 1407-1410

Hepatitis C virus (HCV) infection affects nearly 4 million persons and causes an estimated 12,000 deaths each year in the United States (1). For the 10-year period from 2010 to 2019, the direct medical cost of chronic HCV infection is projected to exceed $10.7 billion, the societal cost of premature mortality attributed to HCV infection is projected to be $54.2 billion, and the cost of morbidity from disability associated with HCV infection is projected to be $21.3 billion (2). The Institute of Medicine recently recommended a comprehensive evaluation of the national hepatitis B and C surveillance system (3). Complete and timely surveillance data are essential for early identification and response to outbreaks and for implementation of evidence-based prevention strategies.

To assess these attributes, CDC compared acute hepatitis C surveillance data reported in 2008 from the National Notifiable Diseases Surveillance System (NNDSS) and the Emerging Infections Program (EIP), which conducts enhanced surveillance for acute hepatitis C in selected states. This report summarizes the results of that analysis, which indicated that 26 (22%) of 120 cases reported from EIP-funded sites were missing from NNDSS. Data on race and major HCV risk factors were missing from 22% and 60% of reports in NNDSS, compared with 8% and 25% of reports in EIP, respectively. The mean duration between diagnosis and reporting of the case to the state health department was 30 days (range: 0--298 days) in NNDSS compared with 19 days (range: 0--350 days) in EIP sites.

These findings underscore that enhanced surveillance for acute hepatitis C improves the completeness and timeliness of the data.

Reporting of Acute Hepatitis C Cases Through NNDSS

Health-care providers, hospitals, and laboratories are required to send reports of cases of HCV infection to state and local health departments that include them within their jurisdiction. Reports meeting the Council of State and Territorial Epidemiologists (CSTE) and CDC case definition for acute hepatitis C* are entered into each state's notifiable disease surveillance system. States voluntarily transmit case reports to CDC on a weekly basis via the National Electronic Telecommunications System for Surveillance (NETSS). NETSS is a system of computerized record formats used to transmit NNDSS data from health departments to CDC.

The NETSS case reporting form includes data on demographics (e.g., age, date of birth, sex, race, and ethnicity), clinical information (e.g., date of onset, date of diagnosis, jaundice, hospitalization, and death), and risk factor exposures occurring 6 weeks to 6 months before illness onset (e.g., injection-drug use, sexual/household contact with a person with hepatitis, blood transfusion with dates of transfusion, dialysis, needle stick, tattoo, surgery, acupuncture, and being a health-care worker who has contact with human blood). Laboratory results are not transmitted to CDC because the electronic infrastructure in NETSS does not include fields for laboratory findings.

Reporting of Acute Hepatitis C Cases Through EIP Sites

EIP hepatitis surveillance§ collects more extensive information compared with NETSS. In addition to demographics, the EIP form includes clinical data (e.g., date of diagnosis, symptoms, jaundice, hospitalization, pregnancy, death from hepatitis, liver function tests, hepatitis laboratory test results, and reason for testing) and risk factor exposures occurring 2 weeks to 6 months before illness onset (i.e., contact with a person with hepatitis and the type of contact, number of male and female sex partners, previous history of treatment for sexually transmitted diseases, use of illicit drugs [both injection and noninjection], hemodialysis, injury with sharp object contaminated with blood, blood/blood products transfusion with dates of transfusion, receipt of intravenous infusions and/or injections in outpatient settings, exposure to blood, medical/dental/public safety worker employment with frequency of exposure to blood, presence of tattoo/piercing and location where they were performed, dental work/surgery, hospitalization, residence in a long-term--care facility, and incarceration). In 2008, six EIP sites (Connecticut, Colorado, Minnesota, Oregon, 34 counties in New York State, and New York City) were funded by CDC to conduct enhanced acute hepatitis C surveillance. The catchment area of these sites comprises approximately 28 million persons. Site staff members investigate physician and laboratory reports submitted to health departments and directly contact the health-care providers to complete the demographic, clinical, and risk factor information listed in the EIP case reporting form; reports that fulfill the acute HCV infection case definition are sent monthly to CDC.

Comparison of NNDSS and EIP Surveillance

Cases reported to NNDSS and EIP were matched by a common case identifier and date of birth. CDC evaluated data quality by measuring the completeness of information on demographic and clinical variables, including age, sex, race, ethnicity, jaundice, and major HCV infection risk factors, in both NNDSS and EIP systems. Sensitivity and positive predictive value of NNDSS for reporting acute hepatitis C cases were calculated for the sites conducting both NNDSS and EIP surveillance by using EIP sites' surveillance as the reference. Timeliness of case reporting was based on calculating the interval between the date of diagnosis and the date of reporting of the case to the state health department.

In 2008, a total of 877 cases of acute hepatitis C were reported to CDC by NNDSS via NETSS from 40 states. A total of 120 cases were reported from the six EIP sites; in comparison, 102 cases were reported from NNDSS in states that also are funded for EIP. Although age and sex data were nearly complete in NNDSS and EIP sites, race and ethnicity were missing in 22% and 41% of reports in NNDSS, compared with 8% and 21% in EIP, respectively. Completeness of demographic information for cases of acute hepatitis C in NNDSS was substantially higher in the six sites that also have an EIP surveillance system in place, compared with the remaining states that are not funded for enhanced surveillance (Table 1). Presence or absence of jaundice was reported in 63% of cases from NNDSS and 98% of cases reported from EIP.

Completeness of information on major HCV infection risk factors ranged from 15% to 46% for NNDSS, compared with 70% to 77% in EIP sites. Completeness of clinical and risk factor indicators did not differ substantially in NNDSS when comparing states that have EIP surveillance to those that are not part of EIP.

Comparison of the cases that were reported from NNDSS and in the six sites funded for EIP surveillance revealed that 26 cases reported in EIP were missing from NNDSS; however, only eight cases that were reported to NNDSS were not reported to EIP (Table 2). Considering EIP as the reference, sensitivity and positive predictive value of NNDSS were 78% (94 of 120) and 92% (94 of 102), respectively.

Complete information on both the date of acute hepatitis C diagnosis and date of case reporting to the state health department was available for 39 cases (4%) in NNDSS and 72 cases (60%) in EIP sites. The mean duration between diagnosis and reporting of the cases to the state health department was 30 days (range: 0--298 days) in NNDSS, with 74% and 77% of the cases being reported within 7 days and 1 month of diagnosis, respectively. Among EIP sites, the mean duration between diagnosis and reporting of the cases to the state health department was 19 days (range: 0--350 days), with 80% and 94% of the cases being reported within 7 days and 1 month of diagnosis, respectively.

Reported by

RM Klevens, DDS, Div of Viral Hepatitis, National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention; RA Tohme, MD, EIS Officer, CDC.

Editorial Note

The findings in this report show that the quality of data from NNDSS is not on par with data reported from EIP surveillance sites. Clinical and risk factor information for a substantial proportion of the cases was missing from NNDSS. As shown in previous studies, NNDSS had a substantial proportion of cases with missing data on race and ethnicity (4,5). Hepatitis C disproportionately affects non-Hispanic blacks compared with persons of other races (1). Therefore, surveillance data should include race and ethnicity information to reduce disparities through targeted prevention programs (4). In addition, because of limited resources, several states are not able to handle the volume of laboratory case reports received, which affects timeliness of reporting. In 2009, a total of 27 jurisdictions had backlogs of HCV data, with an average of 6,200 reports that needed to be entered (3). Accurate, timely, and complete surveillance data are needed to identify and respond to outbreaks in a timely fashion, to guide and evaluate prevention strategies, and to allow for the early initiation of treatment, leading to an ultimate decrease in health-care costs.

Health departments using EIP enhanced surveillance have shown its effectiveness in identifying clusters or outbreaks of hepatitis C infection. For example, the New York State Department of Health detected a cluster of 20 hepatitis C infections among young injection-drug users by conducting enhanced surveillance of HCV infections reported among persons aged <30 years (6). Similarly, EIP enhanced surveillance of acute hepatitis C infections allowed the identification of health-care--associated acute hepatitis C outbreaks.

Early identification of acute hepatitis C infection is essential to prevent chronic infections and subsequent liver cancer and associated health-care costs. In fact, early treatment of hepatitis C prevents chronic disease in more than 90% of persons treated during the acute phase of the infection (7,8) and more than doubles the chance of achieving a sustained virologic response (absence of HCV RNA 24 weeks after discontinuation of therapy reflecting absence of viremia and normal liver function), compared with that achievable by treating chronic hepatitis C infection (9). The rate of achieving a sustained virologic response is inversely associated with time from acute HCV infection diagnosis (9). In addition, early treatment contributes to lower health-care costs compared with later treatment (8). 

The findings in this report are subject to at least four limitations. First, the data for timeliness calculation were missing from the majority of NNDSS cases, and this might have led to an overestimation of timeliness in NNDSS. Second, estimates of timeliness would have been improved if CDC had been able to assess the duration between diagnosis and reporting to the local rather than the state health department. However, this information was not available from NETSS. Third, the states where enhanced reporting of acute hepatitis C was implemented were not selected at random; consequently, the observed differences between the performances of the NNDSS and EIP surveillance systems might not all be attributable to differences between the surveillance systems themselves. Finally, this report could not assess the proportion of missed diagnoses of acute HCV infections at the provider level, which would contribute to underreporting of cases to both NNDSS and EIP.

The comparison of NNDSS (a passive surveillance system) with EIP (an enhanced surveillance system) indicates that accuracy and timeliness of reporting for acute HCV infections were improved through enhanced surveillance. Expanding enhanced surveillance for acute hepatitis C to the national level would detect an estimated additional 22% of acute hepatitis C cases. However, because of budget constraints, enhanced surveillance for acute HCV infections is not implemented nationwide.

The Institute of Medicine report recommended a surveillance system comparable to that of human immunodeficiency virus (HIV) surveillance (3). HCV and HIV infections are similar in that many of the cases are asymptomatic and early identification and initiation of treatment would prevent transmission, complications, and deaths. However, although HIV case ascertainment requires a single laboratory test, ascertainment of a single case of acute HCV infection requires an average of four laboratory reports (10).

Based on the findings described in this report, additional resources for acute hepatitis C surveillance could enhance substantially the quality of the data on which prevention interventions are based, and in turn, could reduce morbidity and mortality associated with HCV infection. Nonetheless, a cost-benefit analysis to assess the usefulness of implementing EIP enhanced surveillance for acute hepatitis C at the national level is needed.


This report is based, in part, on contributions by state and territorial health departments and EIP sites conducting enhanced hepatitis surveillance.


  1. Armstrong GL, Wasley AM, Simard EP, McQuillan GM, Kuhnert WL, Alter MJ. The prevalence of hepatitis C virus infection in the United States, 1999 through 2002. Ann Intern Med 2006;144:705--14.
  2. Wong JB, McQuillan GM, McHutchinson JG, Poynard T. Estimating future hepatitis C morbidity, mortality, and costs in the United States. Am J Public Health 2000;90:1562--9.
  3. Institute of Medicine. Hepatitis and liver cancer: a national strategy for prevention and control of hepatitis B and C. Colvin HM, Mitchell, AE, eds. Washington, DC: National Academies Press; 2010.
  4. Buehler JW, Stroup DF, Klaucke DN, Berkelman RL. The reporting of race and ethnicity in the national notifiable diseases surveillance system. Public Health Rep 1989;104:457--65.
  5. CDC. Reporting of race and ethnicity in the national notifiable diseases surveillance system, 1990. MMWR 1992;41:653--7.
  6. CDC. Use of enhanced surveillance for hepatitis C virus infection to detect a cluster among young injection drug users---New York, November 2004--April 2007. MMWR 2008;57:517--21.
  7. Jaeckel E, Cornberg M, Wedemeyer H, et al. Treatment of acute hepatitis C with interferon alfa-2b. N Engl J Med 2001;345:1452--7.
  8. Dintsios CM, Haverkamp A, Wiegand J, et al. Economic evaluation of early monotherapy versus delayed monotherapy or combination therapy in patients with acute hepatitis C in Germany. Eur J Gastroenterol Hepatol 2010;22:278--88.
  9. Corey KE, Mendez-Navarro J, Gorospe EC, Zheng H, Chung RT. Early treatment improves outcomes in acute hepatitis C virus infection: a meta-analysis. J Viral Hepatitis 2010;17:201--7.
  10. Klevens RM, Miller J, Vonderwahl C, Speers S, et al. Population-based surveillance for hepatitis C virus, United States, 2006--2007. Emerg Infect Dis 2009;15:1499--502.

What is already known on this topic?
Hepatitis C is a major public health problem in the United States and contributes to increased health-care costs. Complete and timely surveillance data for hepatitis C infections lead to a timely identification and response to outbreaks, help guide and evaluate prevention strategies, and enable early initiation of treatment, leading to an ultimate decrease in health-care costs. 

What is added by this report?
Reporting of acute hepatitis C in routine national surveillance missed approximately 22% of cases reported by sites funded through the Emerging Infections Program. In addition, 60% of the cases in the National Notifiable Diseases Surveillance System lacked information about hepatitis C risk factors.

What are the implications for public health practice?
Availability of a nationwide enhanced acute hepatitis C surveillance system improves case detection as well as completeness and timeliness of acute hepatitis C data. This is essential for a timely public health action and early initiation of treatment, both of which contribute to the prevention of advanced liver disease and a decrease in associated health-care costs.

Early treatment for HIV/HCV coinfections.

Hepatitis C treatment pipeline

Tracy Swan
Dedicated to Dr. Roy Arad

Although curable, hepatitis C virus (HCV) has been described by the World Health Organization (WHO) as a “viral time bomb” due to both its prevalence (3% of the world’s population, or 170 million people, have been infected) and potential for causing serious, life-threatening complications (WHO 2010). Up to 130 million people have chronic hepatitis C, and 20 to 30% of them—between 13 and 19.5 million people—will develop cirrhosis if untreated or unsuccessfully treated. People with cirrhosis are at risk for liver cancer (hepatocellular carcinoma; HCC) and liver failure. In fact, more than 365,000 people die each year from these HCV complications (Perz 2006).

Worldwide, an estimated 4–5 million people are coinfected with HIV and hepatitis C (Alter 2006). They need more effective and tolerable HCV treatment. In places where people have access to antiretroviral therapy, end-stage liver disease from HCV coinfection has become a leading cause of death among HIV-positive people (Weber 2006). This is because HIV accelerates HCV progression and increases the likelihood of complications: HIV doubles the risk of cirrhosis, and immunodeficiency increases the risk of HCC (Clifford 2008; Graham 2001). Unfortunately, HCV treatment with the current standard of care (SOC) is less effective for coinfected people than their HCV monoinfected counterparts (Carrat 2004; Chung 2004; Torriani 2004).


Approximately half of the people who undergo hepatitis C treatment are cured. In the near future more people with hepatitis C will be cured, some in half the time required now. Scientific advances and keen pharmaceutical interest have led to a flurry of HCV drug development; more than thirty drugs have entered clinical trials. Sales of HCV drugs, which have been plummeting in the U.S., are expected to increase from $2.3 billion to $4.5 billion by 2017 as new drugs enter the marketplace. The U.S. ($1.9 billion), and the E.U. ($1.7 billion) will be major consumers (Datamonitor 2009).

Oral drugs (known as direct-acting antivirals, or DAAs) that specifically target certain steps in the hepatitis C virus life cycle are in late-stage development. In 2011, the U.S. Food and Drug Administration (FDA) approval of two HCV protease inhibitors, boceprevir and telaprevir, is expected. But pegylated interferon (also known as peginterferon) and ribavirin—the current standard of care for hepatitis C—will remain as the therapeutic backbone for the first few generations of HCV drugs.

Peginterferon and ribavirin work by killing infected cells (immunologic effect) and protecting new cells from hepatitis C by preventing HCV replication (antiviral effect). Nobody knows whether a combination of DAAs will cure HCV by preventing the virus from reproducing (an approach that has been successful for treating, but not eradicating, HIV). Peginterferon (or another therapy that stimulates the immune response to HCV) may still be required to cure HCV.

Everyone would like to be rid of interferon. It is a huge barrier to HCV treatment access, uptake, and completion because of its cost (~$25,000 per year), medical contraindications, and many side effects. Even when HCV treatment is readily available at no cost, tolerability is a problem: only one out of 56 people who received HCV treatment through the Veteran’s Administration completed their regimen (Butt 2009).

Hopefully, DAA combinations will become the standard of care. By 2013, results from a trio of groundbreaking trials will be available. These studies combine two DAAs, with or without peginterferon and ribavirin. Study populations and drugs differ (in treatment-naive people, a protease inhibitor/non-nucleoside polymerase inhibitor combination; in prior null responders, a protease inhibitor plus an NS5a inhibitor), but if successful, these trials will provide initial proof-of-concept for peginterferon-free regimens.

In the meantime, results from the first phase III study of a DAA (telaprevir, an HCV protease inhibitor) plus SOC were reported in May 2010, and others are nearing completion. Several ongoing triple therapy trials—adding a single DAA to SOC—are exploring treatment strategies and duration, and evaluating early predictors of successful treatment. Quad trials—two DAAs plus SOC—will soon be underway as well.

The biggest limitation to DAAs is the emergence or development of drug resistance. Drug resistance means that an organism—such as HCV—is able to grow or reproduce despite presence of levels of a drug that would normally stop it from doing so. HCV makes billions of copies of itself each day. They are not identical; some individual virus particles (virions) have structural changes (mutations). Some mutations may allow the virus to escape from drug pressure, leading to drug resistance. In fact, resistance to one or more DAA classes has already been detected in people who have never used these drugs (Kuntzen 2008; Legrand-Abravanel 2009).

HCV treatment strategies must continue to evolve in order to forestall drug resistance and meet the needs of different populations. Some people cannot use peginterferon and ribavirin, and it is ineffective for ~50%, leaving many unsuccessfully treated people (see box: Terms for HCV Treatment Response by Population and Time Point). But adding a single DAA to SOC will not work for all treatment-experienced people.

So far, it is clear that adding a DAA to SOC therapy is most likely to work for people who relapsed or experienced viral breakthrough. Adding a single drug is less likely to work for people who have HCV that is not responsive to peginterferon, as is the case with treatment nonresponders and null responders. Using two or more DAAs may be effective and lower the risk of drug resistance for non- and null responders, but more research is needed to determine retreatment strategies for these groups.

Terms for HCV treatment response by population and time point

Relapse means that HCV became—and remained—undetectable during treatment, but reappeared within weeks to months after finishing it.
Viral breakthrough means that HCV reemerged after becoming undetectable during treatment.
Non-response means that the hepatitis C viral load drops by two logs (99%) but does not ever become undetectable during treatment.
Null response means that hepatitis C viral load drops by less than one log (10%) after four weeks of treatment, and drops by less than two logs (99%) drop after 12 weeks of treatment.
Time point
Very rapid virological response (vRVR) is a new term, used to indicate that HCV RNA has become undetectable after 14 days of treatment.
Rapid virological response (RVR) means that HCV cannot be detected in the blood after four weeks of treatment. RVR is a significant milestone in response-guided therapy because it predicts sustained virological response (see below) in ~90% of cases—regardless of HIV status, but a person can still be cured in the absence of RVR.
Sustained virological response (SVR) means that no HCV is detectable in a person’s bloodstream six months after completion of treatment. SVR is durable, and linked to reductions in liver-related morbidity and mortailty; HCV is cured.
Extended rapid virlogic response (eRVR) is a newly coined term indicating that HCV RNA has becomes undetectable after 4 weeks of treatment and remains undetectable at week 12.
Partial early virological response (pEVR) means that HCV RNA has dropped by at least two logs (99%).
Complete early virological response (cEVR) means that HCV RNA is undetectable after 12 weeks of treatment. SVR is more likely for people who have a cEVR than people who have a pEVR. Although an early virological response cannot predict who will be cured, it does indicate who will not be cured if they remain on treatment. Since SVR is extremely unlikely in people who don’t have a pEVR or cEVR, HCV treatment is usually discontinued at this point. Sometimes this is called an early stopping rule.
End-of-treatment response (EOT) means that HCV viral load is undetectable at the end of HCV treatment.
SVR-12 means that HCV remains undetectable 12 weeks after completion of treatment. Although it has not been prospectively validated (meaning that researchers have found this to be true by looking back at trial results rather than planning in advance to see if it is true), SVR-12 is a good predictor of SVR because relapse usually occurs within a few weeks after treatment completion.

HCV treatment: population-specific issues

Hopefully, DAAs will be safe and effective for HIV/HCV coinfected people, since SOC is less effective for HIV/HCV coinfected people than for people with HCV monoinfection (see Table 1: HCV Treatment Outcomes, by Population). Coinfected people usually have higher HCV viral loads (HCV RNA) than people with HCV alone. A less effective backbone and a high hepatitis C viral load increase the risk for drug resistance, so coinfected people may require treatment with more than one DAA. But DAAs may interact with some antiretroviral agents, complicating treatment of both viruses. Coinfected people and their medical providers are awaiting results from a pair of ongoing DAA studies in HIV/HCV coinfected people.

The safety and efficacy of DAAs have yet to be explored—or have not been adequately explored—in other key populations. No studies have been initiated in transplant candidates and recipients, despite the urgent need for such studies. Only a small proportion of people with cirrhosis have been enrolled in DAA trials to date. Enrollment of African Americans, Latinos, and Latinas has been inadequate. Although they constitute the highest-prevalence population, people who use drugs are usually excluded from clinical trials, even when they are ready and willing to participate.

Table 1. HCV Treatment Outcomes, by Population

Treatment with peginterferon plus ribavirin (weight-based or flat dosing) for 24–72 weeks; HCV genotype 1 unless indicated

International Registration Trials: HCV Monoinfection (reference)
Study and Date Source Population SVR
Fried, 2002; Manns 2001 Clinical trial HCV genotype 1 42–44%
International Trials: HIV/HCV Coinfection
Study and Date Source Population SVR
Carrat 2004 (Europe) Chung, 2004 (U.S.)
Laguno, 2004 (Europe)
Torriani 2004 (international)
Clinical trial HIV/HCV genotype 1 Carrat: 21% Chung: 14%
Laguno: 38%
Torriani: 29%
Clinical Practice: U.S. and Non-U.S.
Study and Date Source Population SVR
Borroni 2008 Non-U.S. clinical practice (Italy) HCV genotype 1 46%
Feuerstadt 2009 U.S.-based faculty practice (FP) and clinic (C) HCV genotype 1 56% Hispanic, 27% African American, 9% Caucasian, 8% other Overall: 14% FP: 27%
C: 15%
Gheorghe 2007 Non-U.S. clinical practice (Romania) HCV genotype 1 55.9%
Jacobson 2007 U.S. clinical trial (community and academic setting) Genotype 1; fixed-dose ribavirin (FDR) vs. weight-based ribavirin (WBR) FDR: 28.9% (overall) vs. 10.1% (African American) WBR: 34% (overall) vs. 20.7% (African American)
Lee 2006 Non-U.S. clinical practice (Canada) Cirrhosis vs. noncirrhotic, HCV genotype 1 34% (cirrhotic) vs. 41% (noncirrhotic)
African Americans: Clinical Trials and Clinical Practice
Study and Date Source Population SVR
Conjeevaram 2006 Clinical trial African American, HCV genotype 1 28% (vs. 52% among Caucasians)
Jeffers 2004 Clinical trial African American, HCV genotype 1 26% (vs. 39% among Caucasians)
Muir 2004 Clinical trial African American, HCV genotype 1 19% (vs. 52% among Caucasians)
Satapathy 2010 Clinical practice, retrospective review African American, HCV genotype 1 16.1%
Srivastava 2005 Clinical practice African American, HCV genotype 1 19% (vs. 24% among Caucasians)
Latino Populations: Clinical Trials and Clinical Practice
Study and Date Source Population SVR
Rodriguez-Torres 2009 Clinical trial Latino, HCV genotype 1 34% (vs. 49% among Caucasians)
Satapathy 2010 Clinical practice, retrospective review Latino, HCV genotype 1 13.7%
Yu 2009 Clinical practice, retrospective review Latino and Caucasian, HCV genotypes 2 and 3 65.9% (vs. 87.3% among Caucasians)
Asian Population: Clinical Trial
Study and Date Source Population SVR
Liu 2008 Clinical trial Asian, HCV genotype 1 76% (after 48 weeks of treatment)
Prior Relapse/Nonresponse to Standard or Peginterferon plus RBV
Study and Date Source Population SVR
Berg 2006 Clinical trial Relapse after 24 weeks of peginterferon/RBV 51% (retreated for 48 weeks)
Sagir 2007 Clinical practice Nonresponders to standard interferon/ribavirin 4%
Scotto 2008 Clinical trial Nonresponders to standard interferon/ribavirin ~19%
Yoshida 2009 Clinical practice HCV genotype 1, prior relapse/nonresponse to peginterferon plus RBV 65% (prior relapse) 17% (prior nonresponse)
People with Cirrhosis
Study and Date Source Population SVR
Lee 2006 Clinical practice People with bridging fibrosis and cirrhosis (stages F3 and F4) 34%
Di Marco 2007 Clinical trial People with cirrhosis and portal hypertension (low-dose peginterferon and low-dose ribavirin) 11.3%
Iacobellis 2007 Open-label, single-arm study People with decompensated cirrhosis; 24 weeks of treatment (low-dose peginterferon; standard-dose ribavirin) 7%
Iacobellis 2009 Open-label, single-arm study People with decompensated cirrhosis; 48 weeks of treatment (standard-dose peginterferon and ribavirin) 16%
Transplant Recipients
Study and Date Source Population SVR
Hanouneh 2008 Clinical practice Transplant recipients; full-dose peginterferon and ribavirin 23%
Lodato 2008 Clinical trial; response-guided, open-label study Transplant recipients; 48 weeks of low-dose peginterferon and standard-dose ribavirin 26%
Zimmermann 2007 Open-label study Transplant recipients, genotype not specified 19%
Injection Drug Users (IDUs)
Study and Date Source Population SVR
Bruggmann 2008 Clinical Practice Active IDU; HCV genotype not specified 69.3% (versus 59.8% among control group of non-users)
Hellard 2009 Meta-analysis Active IDUs; genotype not specified Median 54% Range 18.1 to 94.1%

HCV treatment access

Patent protection of peginterferon extends until 2016 (Peg-Intron®) or 2017 (Pegasys®) in the United States. The high cost of peginterferon drastically limits access to HCV treatment; it is unavailable to most of the world’s 130 million chronically infected people. According to Viral Hepatitis: Global Policy, a 2010 report from the World Hepatitis Alliance, over 80% of low income countries want assistance to improve access to HCV (and hepatitis B) treatment.

Lack of access to HCV treatment is unacceptable. Pharmaceutical companies can remedy this situation. They have an opportunity to save millions of lives while generating unanticipated revenue and goodwill. Global access to peginterferon and DAAs can—and ought to be—facilitated by these and other measures:
  • adopting a high-volume, low-profit strategy for low and middle income countries
  • registering HCV treatments in all countries
  • granting licenses to generic manufacturers supplying low- and middle-income countries.

Moving forward: HCV drug development

Making sense of the flood of data from HCV trials is difficult. New acronyms appear after each scientific meeting (see box: Terms for HCV Treatment Response by Population and Time Point); HCV treatment duration and strategy vary according to the characteristics of each drug and the populations it is studied in; and trial designs are becoming more complex. Interim reporting (at 4 and 12 weeks) and incomplete data (from press releases, posters, and brief presentations at conferences) add to the confusion. For example, in May 2010, Vertex issued a press release with results from ADVANCE, an international phase III trial of triple combination therapy (telaprevir plus SOC) in treatment-naive people with HCV genotype 1. They reported an overall SVR of 75% (after 12 weeks of a telaprevir-based regimen plus SOC) without specifying treatment duration. A closer look at the data revealed that SVR for short-course treatment (24 versus 48 weeks) dropped to ~52%, still a significant improvement over SOC.

Ongoing studies are exploring DAA combination studies, shorter-course treatment, and response-guided therapy. Boehringer-Ingelheim, Bristol-Myers Squibb (BMS), Gilead, and Vertex have launched multidrug studies; these are proceeding in parallel with trials adding a single DAA to standard of care. Abbott, Anadys, Idenix, Merck, and Pharmasset have drugs from different classes in clinical development, but have yet to announce combination studies.

A tantalizing glimpse of an interferon-free future comes from Roche/Genentech’s pioneering INFORM-1, a two-week proof-of-concept study combining danoprevir, an HCV protease inhibitor, with RG7128, an HCV polymerase inhibitor. The two drug combination worked well in treatment-naive and treatment-experienced study participants with HCV genotype 1. INFORM-3, a longer combination study, has been delayed by a serious safety issue—elevated liver enzyme levels in some people who got the highest dose (900 mg) of danoprevir (in a different trial); this was resolved when the drug was stopped. Results from a study of ritonavir-boosted danoprevir (meaning that another drug, ritonavir, is used to keep danoprevir in the bloodstream longer to make it more effective, with a lower pill burden and frequency of dosing) will determine the optimal dose for future studies.

Meanwhile, four studies combining DAAs (with or without peginterferon and ribavirin) have begun.
  • Boehringer Ingelheim has opened a two-part, peginterferon-sparing study exploring different dosing, and duration of BI 201335 (an HCV protease inhibitor) with different durations of BI 207127 (a non-nucleoside polymerase inhibitor), with or without ribavirin in treatment naïve people with HCV genotype 1.
  • BMS has launched a study combining an HCV protease inhibitor (BMS-650032) with a first-in-class NS5a inhibitor (BMS-790052) with or without SOC, in prior null responders with HCV genotype 1.
  • Gilead has opened a 28-day, two-arm study of GS-9256 (an HCV protease inhibitor plus GS-9190 (a non-nucleoside polymerase inhibitor), with and without ribavirin, followed by SOC in treatment-naive people with HCV genotype 1.
  • Vertex is combining telaprevir (an HCV protease inhibitor) with VX-222 (an HCV polymerase inhibitor) in treatment-naive people with HCV genotype 1. Depending on randomization and early treatment response, participants will receive dual DAAs (followed by SOC if indicated) or quad therapy (DAAs plus SOC).

Characteristics of the class: HCV protease inhibitors

HCV-specific protease inhibitors will be the first DAA class available. This family of drugs has been used for more than a decade to treat HIV (in combination with other antiretroviral drugs). Protease inhibitors block cleaving of viral proteins (which would otherwise be reassembled into new virus particles) in the same way that inserting something between the blades of a scissor prevents them from cutting.

The first generation, Merck/Schering Plough’s boceprevir and Vertex/Tibotec’s telaprevir, are in phase III; barring unforeseen circumstances, approval is expected in early 2011. Although treatment strategies and durations differ (see Table 2: Dueling HCV Protease Inhibitors), adding one of these drugs to SOC has significantly boosted SVR among people with HCV genotype 1.

Table 2. Dueling HCV Protease Inhibitors
Drug Dosing/Pill Burden SVR in Treatment-naive People* Duration of Treatment Strategy Drawbacks
Boceprevir 3 times daily, 12 pills/day 54-56% (triple therapy and lead-in, respectively) 67-75% (triple therapy and lead-in, respectively)
63-66% (lead-in, response-guided therapy or set duration therapy )
24–48 weeks 44–48 weeks
28–48 weeks
Triple therapy, or after a 4-week lead-in with SOC4-week lead-in followed by triple therapy, either response-guided or set duration Anemia; epoetin alfa used by ~50% in phase II; long treatment duration **lack of data in treatment experienced people due to protocol amendments in phase  II; phase III data in treatment experienced people limited to top-line results from a press release
Telaprevir Q8hrs (every eight hours); or possibly Q12hrs (every 12 hours) 6 pills/day (Q8H regimen) 52–61% after 24 weeks

72% (response-guided therapy; this SVR is among people with undetectable HCV RNA at W 4 and W 12)
*A 24-week regimen was also effective for treatment-experienced people: overall: 51%
prior non-responders (31%); prior viral breakthrough (57%); prior relapse (69%)
8–12 weeks of triple therapy followed by 12–16 weeks of SOC alone (24 weeks total) 24-48 weeks Triple therapy followed by SOC Triple therapy followed by SOC Rash (which can be severe), anemia, itchy skin, nausea, vomiting, diarrhea
Kwo P, Lawitz E McCone C, et al. (abstract 4)  HCV SPRINT-1 final results: SVR 24 from a phase  2 study of boceprevir plus PegIFN alpha-2b/ribavirin in treatment naïve subjects with genotype-1 chronic HCV. 44th Annual Meeting of the European Association for the Study of the Liver. 22-26 April, 2009. Copenhagen, Denmark.
McHutchison JG, Everson GT, Gordon SC, et al. Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection. N Engl J Med 2009; April 30; 360:1827–1838.
Merck. Press Release. August 4, 2010.
Vertex Pharmaceuticals. Press releases. May 25 and August 10, 2010.
Adherence to these drugs will be crucial, since resistance to an HCV protease inhibitor—or to the entire class (cross-resistance)—can develop or emerge within days. Adherence to the first generation of HCV protease inhibitors is likely to be challenging: ribavirin is taken twice daily; boceprevir and telaprevir need to be taken three times a day—although a study comparing twice-daily to thrice-daily dosing of telaprevir reported that efficacy was equivalent (Marcellin 2009). Pill count ranges from 6 (telaprevir) to 12 (boceprevir) per day, not including ribavirin.

Known side effects of HCV protease inhibitors include anemia, rash, anal itching and hemorrhoids, fatigue, nausea, vomiting, diarrhea, dysgeusia (bad taste in the mouth or changes in taste), headaches, dizziness, jaundice, and elevated alanine aminotransferase (ALT) and bilirubin.

Table 3. HCV Protease Inhibitors in Development
Agent/Sponsor Status Comments
Phase I/II; HCV genotype 1, treatment-naive Currently being studied with low-dose ritonavir
Phase Ib; HCV genotype 1, treatment-naive and treatment-experienced Once-daily dosing will be explored in future trials
BI 201355
Boehringer Ingleheim
Phase II; HCV genotype 1, treatment-naive and treatment-experienced May be a once-daily drug
Bristol-Myers Squibb
Phase II; HCV genotypes 1 and 4, treatment-naive Genotype 4 and people with cirrhosis added in phase IIb
Phase III; HCV genotype 1, treatment-naive and treatment-experienced Used 3 times daily; large pill burden (12/day); anemia is common side effect; likely to be approved by 2011
CTS 1027
Phase II; HCV genotype 1, null responders 24-week study with SOC
ITMN-191/RG 7227
Phase II; HCV genotype 1 Has been studied with RG 7128, a nucleoside polymerase inhibitor; dose-limiting liver toxicity was resolved with ritonavir boosting
GS 9256
Gilead Sciences
Phase II Being studied in combination with GS 9190, a non-nucleoside HCV polymerase inhibitor
GS 9451
Gilead Sciences
Phase I No other information available.
MK 5172
Phase I; HCV genotypes 1 and 3, males only Demonstrated activity against resis-tant virus in lab studies and chimps
IDX 320
Phase I; healthy volunteers No other information available.
TMC 435350
Phase IIa; HCV genotype 1, treatment-naive and treatment-experienced Favorable dosing (possibly once daily); preliminary data suggests efficacy in treatment experienced
Phase III; HCV genotypes 1, 2, 3, and 4, treatment-naive and treatment-experienced Approval expected by 2011
Vaniprevir (MK 7009)
Phase II; HCV genotype 1, treatment-experienced A phase II trial in treatment-naive people with HCV genotype 1 is slated to open in August 2010
VX 985
Phase I

Characteristics of the class: HCV polymerase inhibitors

Nucleoside, nucleotide, and non-nucleoside polymerase inhibitors have been part of combination HIV treatment for years. Now, analogues of those drugs, made specifically for HCV, are in development. Nucleoside and nucleotide polymerase inhibitors are imperfect copies of nucleotides that insert themselves into hepatitis C RNA. Since they are faulty, other nucleotides cannot attach themselves; in other words, nucleoside and nucleotide polymerase inhibitors cause viral dead ends. Non-nucleoside polymerase inhibitors interfere with HCV replication by binding to the hepatitis C polymerase and preventing viral replication—it’s as if the virus is a car trying to park in a space that just got too small for it.

Some nucleoside/nucleotide polymerase inhibitors have already been discontinued for toxicity, but other candidates in this promising class are moving forward. If these are safe, effective, and tolerable, nucleoside/nucleotide polymerase inhibitors are likely to become the backbone of HCV treatment, since they are active across genotypes and have a high genetic barrier to resistance (meaning that resistance to this family of drugs is less likely to develop than resistance to protease inhibitors and non-nucleoside polymerase inhibitors).

So far, the hepatitis C non-nucleoside polymerase inhibitors in development are active only against HCV genotype 1, and resistance develops quickly. In fact, mutations that confer resistance to non-nucleoside polymerase inhibitors have already been detected in people who have never taken these drugs (Dryer 2009).
It may be possible to combine non-nucleoside polymerase inhibitors, since the HCV polymerase has at least four binding sites.

Side effects reported in trials of nucleoside/tide and non-nucleoside polymerase inhibitors include nausea, vomiting, diarrhea, fever, weakness, flatulence, chills, headache, fatigue, and rash.

Table 4. HCV Polymerase Inhibitors in Development
Non-nucleoside Polymerase Inhibitors
Agent/Sponsor Status Comments
Phases I /II; HCV genotype 1, healthy volunteers and treatment-naive
Phases I /II; HCV genotype 1, healthy volunteers and treatment-naive
ANA 598
Phase II; HCV genotype 1, treatment-naive Twice-daily dosing
Boehringer Ingelheim
Phase I; HCV genotype 1, treatment-naive and treatment experienced Dosing is q.8 h
BMS 791325
Bristol-Myers Squibb
Phase I/II
GS 9190
Gilead Sciences
Phase II; HCV genotype 1, treatment-naive Being studied with SOC and in a combination trial with GS 9256, an HCV protease inhibitor
IDX 375
Phase I; healthy volunteers Possibly once- or twice-daily dosing
Phase II; HCV genotype 1, treatment-naive
Phase II; HCV genotype 1, treatment-naive VX-222 is being studied in combination with telaprevir, an HCV protease inhibitor
Phase II; HCV genotype 1, treatment-naive
Nucleoside/Nucleotide Polymerase Inhibitors
Agent/Sponsor Status Comments
IDX 184 (nucleotide)
Phase IIa; HCV genotype 1, treatment-naive Once-daily dosing
PSI 7977 (nucleotide) Pharmasset Phase IIa; HCV genotype 1, treatment-naive Once-daily dosing
RG 7128 (nucleoside) Roche/Genentech/Pharmasset Phase II; HCV genotypes 1 and 4, treatment-naive; also studied in 20 prior nonresponders with HCV genotypes 2 and 3 Twice-daily dosing

Characteristics of the class: NS5a inhibitors

NS5a inhibitors may have cross-genotype activity, can be used in combination with DAAs from other classes, and are likely to be effective in people who have developed resistance to other DAA classes.

BMS’s first-in-class NS5a inhibitor demonstrated impressive potency after a single 100mg dose.

Longer-term data on this drug, although promising, are limited to 12 weeks.

Side effect profile is unclear so far, aside from reports of headache.

Table 5. NS5a Inhibitors in Development
Non-nucleoside Polymerase Inhibitors
Agent/Sponsor Status Comments
Arrows Therapeutics
Phase I
BMS 790052
Bristol-Myers Squibb
Phase II; HCV genotype 1, treatment-naive and treatment-experienced Studied in treatment-naive people (including people with cirrhosis) with SOC; also being studied in combination with BMS 650032 (protease inhibitor), plus or minus SOC, in null responders
BMS 824393 Phase II (slated to open in July 2010); HCV genotype 1, treatment-naive Study not open as of 4 August 2010
Phase I/II; HCV genotype 1 Also studied as a treatment for liver cancer
Phase I; healthy volunteers

HCV antivirals

Several antiviral agents, including cyclophilin inhibitors, silymarin, an NS4b inhibitor, an HCV entry inhibitor, a serine C-palmitoyltransferase inhibitor, are in development; more detail is available in TAG’s upcoming Hepatitis C Pipeline Report.


Nitazoxanide (Alinia®), was approved in 2002, to treat diarrhea from two intestinal parasites (Cryptosporidium parvum and Giardia lambia). Since then, it has been studied as a treatment for HCV genotypes 1 and 4 with SOC. Initially, nitazoxanide generated significant excitement, but SVR rates have been unimpressive so far, with the exception of a small Egyptian study in people with HCV genotype 4 (See Table 6: Nitazoxanide and SVR).

Nitazoxanide (NTZ) monotherapy is being studied to prevent post-transplant HCV recurrence, and in combination with SOC in HIV/HCV coinfected people who have genotype 1 and have never been treated for hepatitis C.

Table 6. Nitozoxanide and SVR
Study Population SVR Comments
12 weeks of NTZ, followed by 36 weeks of SOC or 12 weeks of NTZ, followed by 36 weeks of peginterferon vs. SOC
HCV genotype 4 61% NTZ + PEG
79% NTZ + SOC
50% SOC
In genotype 4, SVR ranges from 43 to 70% with SOC
4 weeks of NTZ or placebo, followed by 48 weeks of triple therapy (SOC+ NTZ or placebo)
HCV genotype 1, 80%
null responders and nonresponders
7% (NTZ+ SOC) vs. 0%
(SOC + placebo)
Missing data on response to prior treatment in 20%
4 weeks of NTZ or placebo, followed by 48 weeks of triple therapy (SOC+ NTZ or placebo)
HCV genotype 1,
treatment -naive
44% (NTZ + SOC) 32%
(placebo + SOC)

Sources: Antaki 2009; Bacon 2010; Rossignol 2009; Shiffman 2010.

Novel interferons

Although the future of interferon is unclear, some sponsors have gambled on development of novel formulations. These novel formulations offer more convenient dosing, and—perhaps—fewer side effects. Development of delivery devices, such as external pumps or implants, is also underway.

Table 7. Novel Interferon Formulations in Development
Agent/Sponsor Status Comments
Human Genome Sciences/
Phase III; HCV genotypes 1, 2, and 3, treatment-naive and treatment-experienced Dosed every two weeks; efficacy equivalent to peginterferon. The future of albuferon is unclear; European regulatory authorities have delayed its approval, although FDA filing is expected in 2010
Locteron interferon
Biolex Therapeutics
Phase IIb; HCV genotype 1, treatment-naive Dosed every two weeks; may have more favorable side effect profile than peginterferon
PEG Interferon Lambda
Bristol-Myers Squibb/
  Phase II; HCV genotypes 1, 2, 3, and 4, treatment-naive, with the exception of DAA monotherapy for 2 weeks So far, side effect profile has been favorable; possibly because PEG-IFN Lambda binds to a unique receptor with less distribution throughout the body than the interferon alfa receptor
Other strategies to stimulate and enhance HCV-specific immune responses are being explored, including therapeutic vaccines, monoclonal antibodies, toll-like receptor agonists and interleukin-7. More detail will be available in TAG’s upcoming Hepatitis C Pipeline Report.

TAG research recommendations

Study drugs in clinically relevant populations prior to approval, such as African Americans and Latinos/-as, people with cirrhosis, current and former injection drug users, people with a history of psychiatric disorders, and HIV/HCV coinfected persons.

Often, response rates from HCV clinical trials do not apply to “real-life” populations. HCV treatment safety, efficacy, and tolerability must be characterized in high-prevalence populations, particularly those less responsive to SOC; those at risk for rapid progression of liver disease; and those usually excluded from clinical trials. So far, enrollment of African Americans and Latinos/-as in HCV treatment trials has been disappointing, hovering at approximately 10% (Kwo 2009; McHutchison 2009).

TAG continues to track and document enrollment of African Americans and Latinos/-as in clinical trials, and pushes for sufficient enrollment of members of these populations in HCV clinical trials (Chou 2009).

Numerous studies have reported that drug users can be safely and effectively treated with SOC (Bruggmann 2008; Dore 2010; Harris 2010; Hellard 2009). Once they are given access to ongoing mental health care (including medication, if indicated), people with psychiatric disorders can be safely treated (Martin-Santos 2008; Schaefer 2003). Since depression, mood swings, hypomania, and mania are known side effects of interferon, it is sensible for clinical trials to offer a baseline psychiatric assessment, regular screening for neuropsychiatric side effects, and mental health care during clinical trials to avert treatment discontinuation.

TAG works with other activists, regulatory authorities, researchers, the pharmaceutical industry, harm reduction organisations, and clinicians to advocate for trials in representative populations.
HIV accelerates HCV progression, and SOC is less effective for coinfected people than those with HCV monoinfection (see Table 1:HCV Treatment Outcomes, by Population – printed online and in full PDF report). Hepatitis C–associated end-stage liver disease has become a leading cause of death among HIV-positive people in the United States and Western Europe, where HIV treatment is widely available (Weber 2006). Drug interactions between DAAs and HIV drugs may limit use of specific drugs in coinfected people; this must be fully characterised early in development to facilitate HCV treatment trials—and ultimately-safe and effective use of DAAs in coinfected people.

TAG has co-organised three multi-stakeholder meetings on HCV drug development for HIV/HCV coinfected people with the European AIDS Community Advisory Board (ECAB). These meetings paved the way for preapproval HCV treatment trials in HIV/HCV coinfected people by asking that “Trials of novel HCV therapies in HIV/HCV coinfected people should begin before approval is granted for their use in HCV monoinfection, once results from Phase 2B studies are known, and there are indications from earlier toxicology, pharmacokinetic and drug-drug interaction studies that the specific agent, or agents under investigation will not have the potential for significant dru-drug interactions, or other toxicities relevant to HIV.” (Sitges Declaration 2007).

TAG has co-organized three multi-stakeholder meetings on HCV drug development for HIV/HCV coinfected people with the European AIDS Community Advisory Board (ECAB). These meetings paved the way for preapproval HCV treatment trials in HIV/HCV coinfected people by asking that “Trials of novel HCV therapies in HIV/HCV coinfected people should begin before approval is granted for their use in HCV monoinfection, once results from Phase 2B studies are known, and there are indications from earlier toxicology, pharmacokinetic and drug-drug interaction studies that the specific agent, or agents under investigation will not have the potential for significant drug-drug interactions, or other toxicities relevant to HIV.” (Sitges Declaration, 2007). The consensus built at these meetings and continuing pressure from activists has paid off: HCV treatment trials in HIV/HCV coinfected people are now being launched in parallel with phase III. Trials of boceprevir and telaprevir in HIV/HCV coinfected people are underway.

Develop mechanisms to provide early access to DAA combination therapy for people who are ineligible for clinical trials, and cannot wait for their approval.

It is unacceptable that people with the most urgent need lack access to potentially life-saving therapies. Although preapproval access to single or multiple DAAs poses medical, administrative, and regulatory challenges, it has been accomplished in HIV and is certainly feasible for HCV. Regulators, industry, physicians, and community members need to address and surmount barriers to early access.

In Spring 2010, TAG asked regulators and sponsors attending an FDA meeting on preapproval access to DAAs to develop a framework so that sponsors could provide potentially life-saving drugs to high-risk populations without endangering drug development programs.

Study drugs in liver transplant candidates and recipients as soon as it is safe to do so.

Hepatitis C is the leading indication for liver transplantation, accounting for more than 35% of all liver transplants in the United States (Thuluvath 2010). Survival after transplantation is significantly worsened by recurrent HCV, which is difficult to treat; SOC is often ineffective in or intolerable for transplant candidates and recipients (see Table 1: HCV Treatment Outcomes, by Population).

Despite their desperate need for better HCV treatment, clinical trials of new HCV drugs in transplant candidates and recipients are generally last on the list, lagging until drugs have already been approved. HCV clinical trials in transplant candidates and recipients should be launched prior to approval, and should allow use of other experimental agents—an approach used successfully in HIV research.

Clear regulatory guidance is needed to prod sponsors into launching studies in transplant candidates and recipients, as well as in other high-risk populations. For example, panelists at a 2006 FDA meeting on development of novel agents for HCV treatment recommended that “approval of an effective agent in compensated subjects should not be adversely affected by poor outcomes observed in separate studies of decompensated liver disease” (Sherman 2007).

TAG continues to work with patients, activist groups, academic, and community-based researchers, regulatory agencies, and the pharmaceutical industry to ensure that new HCV drugs and treatment strategies are studied in people with the greatest need, as soon as it is safe to do so.

In addition, TAG advocates for:
  • Prioritizing access to single or multiple DAAs for trial participants in the control arm of clinical trials, and those who did not achieve SVR. Crossover or rollover study designs provide access to an experimental drug for people in the control arm. This approach should be broadened to include study participants unsuccessfully treated with single or multiple DAAs, providing that virtual monotherapy (a multidrug regimen containing only one active agent) can be avoided. A cross-company registry of treatment-experienced trial participants should be established, and these participants should be prioritized for enrollment into trials of DAAs from novel classes.
  • Continued characterization of resistance to all classes of DAAs. Further characterization of resistance mutations is needed to optimize HCV treatment with DAAs, although the clinical utility of resistance testing is not clear at present. Further assessment of clinical implications of HCV drug resistance is needed. One way to assess the impact of drug resistance would be to retreat people who acquired drug resistance in monotherapy trials with the same drug, plus SOC.
  • Development of second- and third-line drugs effective against commonly occurring resistance mutations. Adding a single DAA increases the likelihood of SVR for treatment-experienced people, but is not 100% effective. In fact, ~60% of prior nonresponders did not achieve SVR after retreatment with telaprevir plus SOC in Vertex’s PROVE-3 trial (McHutchison 2010). Thus, an increasing population of people resistant to at least one drug, or one class of drugs, is likely. Cross-resistance to HCV protease inhibitors has already been reported. Sponsors should prioritize drugs with a unique resistance profile and a high genetic barrier over “me-too” drugs.
  • Development of drugs with activity against all HCV genotypes. There are at least six HCV genotypes. Most new HCV drugs were designed to be effective against HCV genotype 1, because it is difficult to cure with peginterferon and ribavirin, and it is predominant in the United States, Western Europe, and Japan (major pharmaceutical markets). But some people, such as current and former injection drug users and recipients of blood and blood products in the early to mid-1980s, are infected with more than one HCV genotype, and may require drugs with cross-genotype coverage (Preston.1995; Silva 2010).
    As more people with genotype 1 are cured, and immigration patterns shift, global distribution of HCV genotypes will change. It will not be possible to eradicate HCV without safe and effective drugs for all genotypes.
  • Full characterization of predictors and indicators of response and nonresponse to HCV treatment across populations. Stopping rules may change as HCV treatment evolves. Reliable predictors of response will motivate people to continue their HCV treatment, and facilitate reimbursement for response-guided therapy. In turn, accurate indicators of nonresponse will lower the risk of resistance, spare people from side effects, and save money.
  • Establishment of a system for HCV treatment strategy trials, to facilitate cross-company collaboration. It is time to scale up HCV research. The opportunity to address key clinical questions in the next five to seven years must not be squandered. Sponsors prioritize getting their drugs to market, and the current landscape is highly competitive. But HCV treatment is complex, and a dedicated research network could advance crucial areas—exploration of multi-experimental agent trials, population-specific questions, and development of treatment strategies—that are likely to languish without a public/private research network. This has been a fruitful approach in HIV disease, where policy makers have allocated funds and sponsors have contributed drugs and diagnostics.
    In the meantime, regulators, researchers, sponsors, and community members need to continue the dialogue on launching cross-company collaborations.
  • Studying DAAs for HCV Prophylaxis. There is no postexposure prophylactic strategy for hepatitis C, regardless of exposure type. HCV transmission from occupational exposures ranges from 0.2% to 10% (Corey 2009). Clearly, research on efficacy of DAAs for postexposure prophylaxis for occupational and nonoccupational exposures is warranted.
TAG works with activist partners domestically and internationally to advocate for access to HCV treatment for all who need it.

Additional resources

Information about clinical trials is available at: (accessed 4 June 2010).

HCV Advocate offers conference reporting, news, fact sheets, an up-to-date HCV pipeline chart, and other resources at (accessed on 6th June 2010). provides news and conference reports at (accessed 6 June 2010).

The National AIDS Treatment Advocacy Project provides comprehensive coverage of HCV, HIV, and HBV research, access, treatment, and policy issues at (accessed 6 June 2010).


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