Hepatitis C treatment pipeline

1 July 2010. Related: Pipeline report, Hepatitis coinfection.

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).

Introduction

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.

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

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 naive 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

Sources:

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 naive 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

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

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

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

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

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

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: http://www.clinicaltrials.gov (accessed 4 June 2010).

HCV Advocate offers conference reporting, news, fact sheets, an up-to-date HCV pipeline chart, and other resources at http://www.hcvadvocate.org (accessed on 6th June 2010).

HIVandHepatitis.com provides news and conference reports at http://www.hivandhepatitis.com (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 http://www.natap.org (accessed 6 June 2010).

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