March 21, 2012

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Clinical Infectious Diseases Advance Access published March 19, 2012

Nathan Ford,1,2 Kasha Singh,4 Graham S Cooke,3,5 Edward J Mills,7 Tido von Schoen-Angerer,1 Adeeba Kamarulzaman,8
and Philipp du Cros6

1Me'decins Sans Frontie`res, Geneva, Switzerland; 2Centre for Infectious Disease Epidemiology and Research, University of Cape Town, and 3Africa
Centre for Health and Population Studies, University of KwaZulu-Natal, South Africa; 4Centre for Clinical Microbiology, University College London,
5Faculty of Medicine, Imperial College London, and 6Me'decins Sans Frontieres, Manson Unit, London, United Kingdom; 7Faculty of Health Sciences,
University of Ottawa, Canada; and 8Department of Medicine, Center of Excellence for Research in AIDS, University of Malaya, Kuala Lumpur, Malaysia

Abstract

The need to improve access to care and treatment for chronic hepatitis C virus (HCV) infection in resource-limited settings is receiving increasing attention. Key priorities for scaling up HCV treatment and care include reducing the cost of current and future treatment; simplifying the package of care; identifying opportunities to shift specific tasks to nonspecialists to overcome human resource constraints; service integration with human immunodeficiency virus (HIV) clinics, prison health services, and needle syringe and oral substitution therapy programs; improving surveillance, monitoring, and research; encouraging patient and community engagement; focusing specifically on the needs of vulnerable groups; and increasing financial and political commitment. Many of these obstacles have been addressed in rolling out treatment for human immunodeficiency virus during the last decade, and a number of lessons can be drawn to help improve access to HCV care.

Hepatitis C virus (HCV) infection is a growing public health concern, with an estimated 170 million persons infected globally and 350 000 deaths each year due to hepatitis C-related liver disease [1]. In 2010 the World Health Assembly adopted a resolution promoting integrated and cost-effective approaches to the prevention, control, and management of viral hepatitis and noted in particular the need to address hepatitis in the context of the human immunodeficiency virus (HIV) epidemic [2]. A number of countries in resource-limited settings are providing treatment of HCV infection through dedicated services with reasonable success [3]. Generally, however, access to care remains limited, particularly in poorer regions such as India and sub-Saharan Africa [4].

Challenges to increasing access to treatment of HCV infection in resource-limited settings include the high cost and perceived complexity of treatment, side effects that hamper adherence, long treatment duration, and insufficient political commitment. Early efforts to increase access to antiretroviral therapy (ART) for HIV/AIDS in resource-limited settings were impeded by similar challenges. We reflect on the experience of scaling up access to ART during the last decade and draw lessons for improving access to treatment and care for persons with HCV.

A decade ago, treatment for persons living with HIV/AIDS was unavailable in most developing countries, and there was debate about whether treatment should be considered given the considerable challenges faced [5]. Yet despite these early concerns, >6.6 million persons are now receiving ART in the developing world [6]. Several critical issues had to be confronted before large-scale HIV treatment programs could be established. These are summarized in Table 1 and discussed below.

REDUCING THE COST OF TREATMENT

Until mid-2000, ART cost about US $10 000 per patient per year, and cost-effectiveness studies concluded that treatment should not be prioritized [7]. This equation shifted as generic competition drove down the cost of treatment. This was largely achieved thanks to significant political support by a global alliance of civil society groups, and in particular persons living with HIV/AIDS and health providers, nongovernmental organizations, and academics who worked together as a global coalition for the rights of those with HIV/AIDS to access treatment [5]. In 2001 a generics manufacturer announced that triple therapy could be manufactured for less than a dollar a day. This created a dynamic of global market competition that drove down the price of standard triple therapy from US $10 000 per patient per year to almost US $60. Today, >80% of ART used in low-income and middle-income countries is manufactured by Indian generics firms [8].

Treatment of HCV infection is currently expensive in developing countries. Generic forms of ribavirin are available, but pegylated interferon is patented in a number of low- and middle-income countries, and overall costs of treatment are high: a recent survey of 5 Asian countries reported that public sector prices for a 48-week course of combination therapy range from US $12 000 (Vietnam) to US $18 500 (Indonesia) [9]. Several alternative sources of pegylated interferon have recently been developed that have helped drive down the cost of treatment. In Egypt, for example, a locally manufactured biosimilar of pegylated interferon is produced [10], and market competition has supported a 6-fold reduction in the price of both originator and generic products: a 48-week treatment course of pegylated interferon and ribavirin currently costs less than US $2000 in Egypt. Although comparative safety and efficacy data are limited for generic pegylated interferon products, this nevertheless demonstrates that substantial price reductions are possible.

The World Health Organization (WHO) prequalification scheme has played a critical role in the availability of affordable antiretrovirals. This scheme is used by donors, implementing organizations and many national programs to assure the quality of generically produced antiretroviral drugs [11]. Similarly, quality assurance of antivirals for HCV would give confidence to donors, patients, and implementing organizations and would allow developing countries to fast-track registration of generic and biosimilar sources of antivirals for HCV. Existing biosimilars of pegylated interferon are registered in only a few countries and have not been quality assessed by WHO, although guidance for the evaluation of biosimilars has been published elsewhere [12].

Access to the newest generation of HCV medicines will be critical, because these drugs have the potential to significantly simplify treatment regimens and improve outcomes, offering particular advantages for use in settings with limited facilities [13, 14]. This will likely require concerted public and political mobilization to pressure originator companies to reduce prices and stimulate generic competition.

SIMPLIFYING THE MODEL OF CARE

HIV/AIDS care in developed countries is highly specialized. Treatment initiation decisions are informed by CD4 count and viral load, and treatment regimens are individualized according to genotypic resistance pattern, clinical response, side effects, and patient preference. More than 30 different antiretroviral drugs are currently approved, allowing for frequent medication adjustments.

In resource-limited settings, access to laboratory tests and choice of medication are limited. Guidelines for the management of HIV/AIDS in resource-limited settings developed by the WHO have helped to simplify management by specifying only a limited selection of once- or twice-daily regimens for first- and second-line therapy and recommending a limited set of laboratory tests that are desirable but not essential [15]. The development of antiretroviral agents as fixed-dose combination tablets has greatly helped to standardize and simplify patient care. In addition, low-technology innovative solutions to provision of essential tests have also been pursued, such as dried blood spots for viral load testing [16].

Similar simplification is required to support HCV management in poorly resourced settings. Current guidelines for treatment of HCV infection are from developed country tertiary care settings; include a variety of tests to initiate and guide care, such as regular viral load monitoring; and involve a range of antiviral and supplementary medications. Research to determine the need for each test will be important to make HCV treatment feasible and cost-effective in resource-limited settings.

Recent innovations enabling noninvasive assessment of liver fibrosis have important possible applications in HCV management decisions in resource-limited settings. These range from those employing the use of widely available blood tests, such as aspartate transaminase (AST) to platelet ratio (APRI) and potentially portable new technologies, such as transient elastography (eg, FibroScan) [17]. These tests generally perform well in distinguishing mild liver fibrosis from advanced fibrosis and cirrhosis, but clinical decisions for treatment often require the diagnosis of intermediate stages of fibrosis and this limits the usefulness of such tests [18]. Findings of a large European study suggest that the FibroScan technique might be more useful than blood markers [19]. Small, portable FibroScan units make the approach more feasible in resource-poor settings, but problems with unreliable readings in inexperienced hands and maintenance of equipment create significant challenges.

The necessity of other investigations in the treatment of HCV infection, in particular HCV viral load monitoring and genotype tests, is an important consideration in planning implementation of HCV treatment programs in resource-limited and isolated settings. Increasing access to viral load technology is becoming a priority within HIV/AIDS programs, and this could serve to benefit HCV programs [20]. Given the paucity of clinical findings in HCV infection before end-stage disease with hepatic decompensation, the availability of investigations may prove to be a larger hurdle for HCV programs than it has been in the case of HIV. Finally, the relative benefit of interleukin 28B testing, which is increasingly used to help predict treatment response in Western settings, needs careful consideration [21].

HCV program development can also learn from simplification approaches to scaling up treatment for multidrug-resistant tuberculosis. Multidrug-resistant tuberculosis care requires frequent injections, multiple medications, and long durations of treatment. Through models of care that provide psychosocial support and early recognition and management of adverse effects and through the decentralized provision of care, good programmatic outcomes have been achieved [22].

In the treatment of HIV infection, the introduction of less toxic drugs and simplified, fixed-dose combinations has been associated with improved adherence [23]. The arsenal of HCV drugs is rapidly changing, and with recent data on newer oral antiviral agents [24], interferon-free treatment for HCV now seems achievable, offering the possibility of injection-free treatment [25]. Mechanisms for accelerated access to simplified treatment of HCV infection should be prioritized.

The simplification agenda for HCV management will need to take into account the different capacities of different settings. Just as guidelines for ART specify a number of diagnostic tests that, although not essential, are nevertheless highly desirable [15], so recommendations for HCV management will need to strike a balance between what can be done today and what should be the standard for tomorrow.

TASK SHIFTING TO OVERCOME HUMAN RESOURCE SHORTAGES

In developed countries, HIV/AIDS has conventionally been managed by specialist physicians. However, health systems in resource-poor settings where the burden of HIV/AIDS is greatest face a critical shortage of the most basic essential health staff, with some high-burden countries having a 100-fold fewer doctors per population compared with the United Kingdom or United States [26]. To address this challenge, the WHO published guidelines for task shifting, outlining a range of tasks that could, with adequate training and supervision, be delegated to nonphysician clinicians [27]. Randomized trials and cohort studies have subsequently validated the safety and effectiveness of task shifting for the provision of ART [28].

The decentralization of HCV management to lower levels of the health system has been assessed in the United States as a way to improve access to care. Outcomes of HCV treatment provided at community settings with specialist supervision via videoconference were found to be comparable to care provided at a dedicated HCV clinic in a tertiary center [29]. This strategy will help to ensure that care is not limited by a lack of specialists and the need to travel to tertiary level centers. Operational research should be conducted to assess the potential for different models of patient support and define the appropriate skills mix for resource-limited settings.

SERVICE INTEGRATION

The provision of ART as a vertical (disease-specific) program was an important early starting point in the AIDS response, allowing for rapid establishment of services. As programs expanded, integration of HIV/AIDS services into the broader health system has become a priority [30]. Primary care services in general, and clinics for antenatal care, tuberculosis, and sexually transmitted infections in particular, have proved to be important entry points for the diagnosis and treatment of HIV, and integration of services has had an important influence on patient outcomes [31].

Similarly, for HCV services to reach larger numbers of persons in a sustainable way, efforts will need to be made to link HCV prevention and treatment services and integrate treatment and care with other health services in which persons at risk are likely to be identified and where provision of quality of care is possible: needle syringe and oral substitution therapy programs, HIV clinics, and prison health services. The first step would be to increase access to HCV diagnostics in such services.

Integration of HIV management into general health services has had mixed results, providing both positive and negative lessons for HCV care [32]. The resulting literature provides an important resource for HCV management programs. For example, a recent review of integration of HIV and tuberculosis highlights some of the ways in which vertical approaches have led to inefficient and ineffective programming for both diseases [33].

SURVEILLANCE, EVALUATION, AND RESEARCH

During the past decade, significant improvements in HIV disease surveillance have informed service provision and directed research. In contrast, there is a dearth of epidemiological information regarding HCV infection rates in most parts of the world [4]. Improved epidemiological information will be critical in expanding HCV services, and many of the approaches developed to collect information about HIV incidence and transmission could be adapted for use in HCV. Increased information regarding the global scale and burden of the epidemic in different settings will increase awareness of the epidemic. Increased testing for HCV infection will be an important component of accurate disease surveillance and is also critical to treatment and prevention efforts [34]. This is particularly important because the development of appropriate treatment strategies will require accurate information regarding genotype prevalence in different countries.

The use of simplified reporting systems with standardized indicators in ART programs has allowed regular monitoring and the strategic direction of resources to improve service provision through operational research [35]. In the development of treatment programs for HCV infection, building in methods of data collection and recording to allow regular and routine program review will help facilitate ongoing service feedback and improvement and will also help generate evidence around the relative benefits and cost-effectiveness of different program strategies.

The research and development agenda for HCV needs to take better account of the specificities of resource-limited countries. For HIV, factors such as heat stability of medications, minimal monitoring of drug regimens, and simplified drug dosing are important for simplifying care [36]. The consideration of such factors in the process of drug development for HCV could greatly facilitate the adoption of treatments in resource-constrained settings.

PATIENT AND COMMUNITY ENGAGEMENT

In the scale-up of treatment for HIV infection, lack of patient knowledge and stigma are understood to influence uptake of testing and adherence to treatment. Efforts to tackle HIV thus need to address both access to diagnosis and care, as well as community education and stigma reduction components [37]. Similarly, persons with HCV infection are often not aware of their diagnosis or lack access to information about the benefits of treatment [38-41]. Efforts to scale up HCV treatment must tackle community education and stigma issues, especially among intravenous drug users.

Initially, there was considerable concern about the challenge of achieving adequate adherence to ART in resource-limited settings, but reported rates of early adherence in sub-Saharan Africa were found to be better than in North America [42]. Adherence counseling by patient experts or community health workers has been demonstrated to be one of the most effective ways of supporting patient adherence [43], while at the same time relieving the burden on health workers. More recent reviews have documented substantial attrition between diagnosis and initiation of ART, highlighting the need to develop supportive models of care that start at the point of diagnosis [44].

The treatment of HCV infection, like ART for HIV infection, is associated with a range of adverse effects, many of which are nonsevere but can lead to poor treatment adherence. A recent meta-analysis of HCV program outcomes in low- and middle-income settings found relatively low rates of defaulting from care (4%) and low frequency of adverse events leading to treatment discontinuation (4%) [3]. Nevertheless, adherence support interventions for HCV treatment need to be better defined, particularly as a proportion of patients who will be eligible for treatment may be asymptomatic. Treatment literacy programs to increase patientsÕ understanding of HCV disease and treatment, together with dedicated peer support to assist with adherence and social issues, will likely be an effective way to ensure that patients are supported during the course of their treatment. Community engagement in other areas of the care pathway such as testing and screening have proved effective in scaling up access to HIV care [45] and should also be explored for HCV.

The engagement of persons living with HIV has been acknowledged as one of the most important achievements in the AIDS response [46]. Persons living with HIV/AIDS have also played a critical political role through activism to pressure price reductions for antiretroviral drugs, increased funding, and acceleration of research and development [47]. Similar activism is beginning to take shape for HCV and will be critical to making treatment more widely available [48].

ADDRESSING THE NEEDS OF VULNERABLE GROUPS

From the outset, efforts to scale up ART in developing countries have included a specific focus on such populations who, because of oppression and vulnerability [49], have been systematically excluded from access to treatment and care. International reports mapping progress toward universal access to prevention and treatment dedicate specific sections to population groups, such as sex workers, injection drug users, men who have sex with men, and prisoners [50], and international funding mechanisms provide specific funding for programs addressing the needs of vulnerable groups.

Given the high burden of HCV infection among injection drug users [51], increased transmission risk in prisoners, and the substantial overlap between the HIV and HCV epidemics, national and international efforts to support improved access to HCV prevention, treatment, and care should benefit from the positive experiences of expanding ART to vulnerable groups.

FINANCIAL AND POLITICAL COMMITMENT

The dramatic reduction in the cost of treatment was essential to shifting the cost-effectiveness equation in favor of the widespread provision of ART. In addition to increased bilateral funding from a number of Western governments, several international funding streams were established to support ART scale-up, notably the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM), and the US President's Emergency Plan for AIDS Relief [52].

To support an international effort to increase access to treatment and care for HCV infection, dedicated funding will be required to support the expansion of access to diagnostics and treatment and the promotion of operational research to develop adapted models of care. The GFATM is already providing some, albeit limited, funding for HCV treatment for individuals coinfected with HCV and HIV, and other donors, such as UNITAID, should explore how they can support HCV care [53]. However, recent reductions in donor contributions to GFATM threaten to limit the number of programs that can be supported [54]. Political commitment from the national governments of countries most affected by HIV/AIDS has also been an essential driver of the global response to HIV and will be critical in enabling the provision of HCV treatment and care in institutions under the management of correctional services.

CONCLUSIONS

Expanding access to hepatitis treatment in resource-limited settings will require a dedicated effort to overcome practical and political challenges. This also applies to care and treatment for persons with hepatitis B virus infection [55], for which many of the lessons outlined in this article apply. Perhaps the most important lessons from the scaling up of ART during the last decade is that this will not happen without clear political commitment, and the engagement of civil society to hold policy makers and drug manufacturers to account. Recent demonstrations by activists in India to call for reduced drug prices for hepatitis treatment could be the first step toward reducing the present inequality where hepatitis treatment and care are, for the most part, available only to patients who are fortunate enough to live in the developed world.

Source

ScienceDaily (Mar. 20, 2012) — Mount Sinai School of Medicine researchers have discovered that marijuana-like chemicals trigger receptors on human immune cells that can directly inhibit a type of human immunodeficiency virus (HIV) found in late-stage AIDS, according to new findings published online in the journal PLoS ONE.

Medical marijuana is prescribed to treat pain, debilitating weight loss and appetite suppression, side effects that are common in advanced AIDS. This is the first study to reveal how the marijuana receptors found on immune cells -- called cannabinoid receptors CB1 and CB2 -- can influence the spread of the virus. Understanding the effect of these receptors on the virus could help scientists develop new drugs to slow the progression of AIDS.

"We knew that cannabinoid drugs like marijuana can have a therapeutic effect in AIDS patients, but did not understand how they influence the spread of the virus itself," said study author Cristina Costantino, PhD, Postdoctoral Fellow in the Department of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine. "We wanted to explore cannabinoid receptors as a target for pharmaceutical interventions that treat the symptoms of late-stage AIDS and prevent further progression of the disease without the undesirable side effects of medical marijuana."

HIV infects active immune cells that carry the viral receptor CD4, which makes these cells unable to fight off the infection. In order to spread, the virus requires that "resting" immune cells be activated. In advanced AIDS, HIV mutates so it can infect these resting cells, gaining entry into the cell by using a signaling receptor called CXCR4. By treating the cells with a cannabinoid agonist that triggers CB2, Dr. Costantino and the Mount Sinai team found that CB2 blocked the signaling process, and suppressed infection in resting immune cells.

Triggering CB1 causes the drug high associated with marijuana, making it undesirable for physicians to prescribe. The researchers wanted to explore therapies that would target CB2 only. The Mount Sinai team infected healthy immune cells with HIV, then treated them with a chemical that triggers CB2 called an agonist. They found that the drug reduced the infection of the remaining cells.

"Developing a drug that triggers only CB2 as an adjunctive treatment to standard antiviral medication may help alleviate the symptoms of late-stage AIDS and prevent the virus from spreading," said Dr. Costantino. Because HIV does not use CXCR4 to enhance immune cell infection in the early stages of infection, CB2 agonists appear to be an effective antiviral drug only in late-stage disease.

As a result of this discovery, the research team led by Benjamin Chen, MD, PhD, Associate Professor of Infectious Diseases, and Lakshmi Devi, PhD, Professor of Pharmacology and Systems Therapeutics at Mount Sinai School of Medicine, plans to develop a mouse model of late-stage AIDS in order to test the efficacy of a drug that triggers CB2 in vivo. In 2009 Dr. Chen was part of a team that captured on video for the first time the transfer of HIV from infected T-cells to uninfected T-cells.

Funding for this study was provided to Drs. Chen and Devi by the National Institutes of Health in Bethesda, Maryland. Dr. Costantino is supported by a National Institutes of Health Clinical and Translational Science Award grant awarded to Mount Sinai School of Medicine.


Story Source:

The above story is reprinted from materials provided by Mount Sinai Medical Center, via Newswise.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.


Journal Reference:

  1. Cristina Maria Costantino, Achla Gupta, Alice W. Yewdall, Benjamin M. Dale, Lakshmi A. Devi, Benjamin K. Chen Cristina Maria Costantino. Cannabinoid Receptor 2-Mediated Attenuation of CXCR4-Tropic HIV Infection in Primary CD4 T Cells. PLoS ONE, 20 Mar 2012 DOI: 10.1371/journal.pone.0033961

Source

Act Now: End Federal Funding Ban on Syringe Exchange Programs

capitolblog

March 21, 2012 | Andrea Levario

As we told you back in December, House Republicans turned their backs on sound science when they reintroduced and passed legislation reinstating the ban on federal funding for syringe exchange programs (SEP). Today, HRC is joining with our partners in the HIV/AIDS community in a National Call to Action on Syringe Exchange.

Injection drug use (IDU) has directly and indirectly accounted for 36 percent of AIDS cases in the U.S. and 68 percent of current hepatitis C infections. By providing clean, sterile syringes in exchange for used ones, SEPs directly reduce the transmission of HIV, hepatitis, and other blood-borne infections frequently spread through sharing syringes. These programs are often one of a wide range of social services offered by organizations along with HIV testing and education, rehabilitation, and treatment for drug addiction. In 2008, the Centers for Disease Control and Prevention concluded that the incidence of HIV among intravenous drug users had decreased by 80 percent in the U.S. over a 20 year period in part due to SEPs. Currently, more than 32 states and the District of Columbia operate SEPs.

In 2009, understanding the importance of this scientifically-proven prevention tool, lawmakers removed the funding ban. But last year, ideology prevailed over science, and the fight against HIV/AIDS took a small step backward. President Obama - who has made strides to end the HIV/AIDS epidemic by announcing and implementing a prevention-based National HIV/AIDS Strategy - included lifting the federal funding ban among his FY 2013 budget priorities.

Help us lift the ban! Call your Senators today and urge them to support scientifically-based prevention programs, and to lift the ban on federal funding for syringe exchange programs. Senators can be reached through the Capitol Switchboard at (202) 224-3121. Tell the operator your state and you will be directed accordingly.

HRC Political Intern Andrew Zapfel contributed to this post.

Source

By Adam Feuerstein 03/21/12 - 07:19 AM EDT

BARCELONA (TheStreet) -- Yesterday, I used the words "misguided," "unfair" and "unworkable" to describe a plan by the European Association for the Study of Liver (EASL) to selectively disclose hepatitis C research abstracts ahead of its important and closely followed conference next month.

I'd like to amend my description of EASL today to include "confused" and "incompetent" because the medical research society can't seem to get straight which date it plans to selectively distribute those research abstracts.

On Tuesday, EASL sent an email to a registered attendee of its International Liver Congress, taking place April 18-22 in Barcelona, explaining that the online posting of research abstracts would be delayed until March 27 due to technical difficulties. Abstracts were originally scheduled for release on March 22.

"Please be advised that there has been a delay with the posting of the abstracts online," EASL's email states. "This year EASL have a new programme in place which will allow only paid registrants and EASL Members access to the abstracts. We have been informed that the programme is still being tested and that it should be ready for posting online on Tuesday, 27 March."

Several sell-side analysts spoke independently to EASL officials Tuesdays and were also told that the release of research abstracts was being delayed until March 27.

But when I asked EASL spokesperson Jacqui Sisto to confirm and further explain the abstract posting delay, she denied it:

"I do not know the source of your information, but it is incorrect. EASL will release the abstracts on March 22 as planned," said Sisto in an email sent Wednesday morning.

Hopefully, EASL will get its act together soon and let us all know when research abstracts will be posted. These abstracts are important because they contain potentially stock-moving clinical data pertaining to new hepatitis C drugs.

EASL's International Liver Congress is the must-follow medical meeting of the spring. Gilead Sciences(GILD_), Bristol-Myers Squibb(BMY_), Abbott(ABT_), Idenix Pharmaceuticals(IDIX_), Vertex Pharmaceuticals(VRTX_) and Merck(MRK_) are among the companies rolling out new clinical data on experimental hepatitis C therapies.

As far as I know, EASL still has no plans to alter its plan to distribute these important research abstracts only to EASL members or registered attendee of the EASL meeting -- a group which includes hedge fund and mutual fund portfolio managers and sell-side analysts, all of whom can pay for early access.

EASL's research abstracts will not be made available to the public. That means a select group of investors will have access to potentially stock-moving clinical data while a majority of investors will be kept in the dark.

Journalists registered to cover the EASL meeting will also be granted early access to hepatitis C research abstracts but they are still barred by EASL's restrictive embargo rules from writing about any new data until the start of the April meeting.

At EASL, amateur hour continues.

--Written by Adam Feuerstein in Boston.

Source


EASL Gives Wall Street's Privileged Investors Sneaky Preview to Key Hep C Data

87753812

By Adam Feuerstein 03/20/12 - 10:45 AM EDT

Update: After this column was published, EASL announced a delay in the release of research abstracts for the International Liver Congress to Tues. March 27.

BARCELONA (TheStreet) -- Investing in hepatitis C drug stocks is a suckers bet this week because the European Association for the Study of the Liver, better known as EASL, has rigged the game so that Wall Street's privileged investors get a sneak peek at new clinical data ahead of an important and closely followed conference next month.

EASL's International Liver Congress, taking place April 18-22 in Barcelona, is the must-follow medical meeting of the spring. Gilead Sciences(GILD_), Bristol-Myers Squibb(BMY_), Abbott(ABT_), Idenix Pharmaceuticals(IDIX_), Vertex Pharmaceuticals(VRTX_) and Merck(MRK_) are among the companies rolling out new clinical data on experimental hepatitis C therapies.

But if you want an advance look at potentially market-moving hepatitis C drug data, you'll have to be an EASL member or a registered attendee of the EASL meeting -- a group which includes hedge fund and mutual fund portfolio managers and sell-side analysts, all of whom can pay for early access.

EASL plans to selectively distribute hepatitis C drug research abstracts to these folks on Thursday. The same documents will not be made available to the public. That means a select group of investors will have access to potentially stock-moving clinical data while a majority of investors will be kept in the dark.

Journalists registered to cover the EASL meeting will also be granted early access to hepatitis C research abstracts but they are barred by EASL's restrictive embargo rules from writing about any new data until the start of the April meeting.

EASL's abstract distribution policy is misguided, unfair and quite frankly unworkable. Smarter medical and scientific groups like the American Society of Clinical Oncology (ASCO) realized years ago that trying to compartmentalize research abstracts was futile. Information cannot be selectivity disclosed and expected not to leak, especially information that will weigh on the market valuations of biotech and drug firms involved in new hepatitis C drug research.

That's why most medical and scientific groups made research abstracts freely available to everyone in advance of major conferences.

Jacqui Sisto, an EASL spokesperson, explained via email that selective disclosure of research abstracts "ensures the integrity of the International Liver Congress." Really? EASL appears to be corrupting its most important meeting, not making it more honest.

EASL's integrity will not be bolstered when analysts and select investors begin madly downloading and discussing new hepatitis C data on Thursday -- taking advantage of the fact that most of the investing public won't have access to the same information.

It's like insider trading -- only perfectly legal, aided and abetted by EASL!

For those investors not fortunate enough to be allowed inside the velvet ropes of EASL's research abstract release party on Thursday, here's a company-by-company summary of the hepatitis C data expected to garner the most attention by Wall Street:

Gilead Sciences:

Data from two separate but similar studies (ELECTRON and QUANTUM), both involving the two-drug combination of GS-7977 plus ribavirin in treatment-naive genotype 1 patients.

Gilead has said results from the QUANTUM study could be announced in a press release early in the second quarter i.e. before the start of the EASL meeting. Investors are sure to scour the EASL web site Thursday for any early patient data that may give a hint about the later '7977 results. Much is riding on the outcomes from these treatment-naive patient studies because '7977's potency was cast in doubt due to poor results in so-called "null responder" patients.

Bristol-Myers Squibb:

Interim results from a phase II study combining Bristol's NS5a inhibitor daclatasavir (BMS-52) with Gilead's GS-7977 in genotypes 1, 2, and 3 is the most highly anticipated data presentation at the EASL meeting this year. The study is important because it will be one of the first glimpses at the Hep C-killing potency of these two classes of direct-acting antivirals combined into a single, all-oral therapy.

If this study is successful, Bristol is expected to swap out GS-7977 for its newly acquired nuke INX-189, gained from the Inhibitex acquisition. Gilead may also capitalize on the study by combining GS-7977 with its own NS5a inhibitor.

Abbott:

Data from a phase II study of its own all-oral Hep C regimen consisting of protease inhibitor ABT-450, a ritonavir booster and the non-nuke polymerase inhibitor ABT-333. The study enrolled treatment naive genotype 1 patients as well as treatment-experienced non-responders.

Merck:

The potential for additional data on its pan-genotypic protease inhibitor MK-5172.

Idenix Pharmaceuticals:

An update on the phase IIb study of nuke IDX-184 plus early data on NS5a inhibitor IDX719.

--Written by Adam Feuerstein in Boston.

Source

It Is Time to Change the Paradigm for Hepatitis C Virus Testing

Clin Infect Dis. (2012) doi: 10.1093/cid/cis047 First published online: March 14, 2012

Sylvie Deuffic-Burban1,2 and Yazdan Yazdanpanah1,3,4

+ Author Affiliations

  1. 1Inserm ATIP-AVENIR ”Modélisation, aide à la décision et coût-efficacité en maladies infectieuses,” Lille
  2. 2Université Lille Nord de France
  3. 3Université Paris-Diderot
  4. 4Service de Maladies infectieuses et tropicales, Hôpital Bichat Claude Bernard, Paris, France
  1. Correspondence: Sylvie Deuffic-Burban, PhD, Inserm ATIP-AVENIR, U995, Parc Eurasanté, 152 rue du Docteur Yersin, 59120 Loos, France (sylvie.burban@neuf.fr).

ARTICLE

In the United States, 2.7–3.9 million persons (1.2%–1.8% of the population) are chronically infected with hepatitis C virus (HCV) [1], and 49%–75% of them are unaware of their HCV status [2, 3]. In some European countries, the HCV prevalence is similar or even higher, and the proportion of persons unaware of their infection is identical. For example, in Spain, approximately 2% of the population is chronically infected with HCV [4], and 65% are unaware of their infection [5]. In Italy, where the prevalence rate is twice as high [6, 7], 55% of HCV-infected persons are unaware of their infection [8]. Because of the asymptomatic nature of chronic hepatitis C, most people infected with HCV are not aware that they have been infected until symptoms of cirrhosis or hepatocellular carcinoma appear, possibly years later. Prevention of these complications requires treatment before patients reach advanced stages of the disease, at which time treatment efficacy is significantly lower than at earlier stages of the disease. The recently marketed direct-acting antiviral drugs can significantly increase the rate of sustained virological response in treatment-naive patients with HCV genotype 1, the most prevalent circulating strain in North America and Western Europe: 70%–75% in patients with moderate fibrosis (fibrosis score ≤ F2) and 50%–60% in those with advanced fibrosis (F3–F4) [914]. HCV-infected patients should therefore be screened at earlier stages of the disease to benefit from a treatment of enhanced efficacy. Moreover, previous mathematical modeling work suggested that HCV antiviral treatment could prevent HCV transmission among injection drug users [15]. The recent availability of new, less aggressive approaches for determining liver fibrosis and suitability for treatment and, more important, of new and considerably more efficacious HCV combinations, underscores the importance of early screening of hepatitis C.

Current US guidelines recommend screening for a history of risk of exposure to HCV virus and testing selected individuals having an identifiable risk factor [16, 17]. Most European countries apply similar screening policies [1822]. However, the high proportion of HCV-infected patients unaware of their infection underscores the limits of this approach and the need to reconsider HCV testing strategies.

Why does a risk-factor-based HCV screening strategy not work? Probably because, as with the human immunodeficiency virus (HIV) setting, patients report their risk status inaccurately, while providers lack the time and expertise necessary to conduct risk evaluation [23]; moreover, targeting can cause anxiety during the patient–provider discussion. When rethinking new HCV screening strategies, we might first consider training clinicians and developing tools, such as behavioral and clinical instruments, to better identify those at high risk of HCV infection. Recommendations and proposals for HCV screening could be expanded to one-time screening of regions or birth cohorts with a high prevalence of HCV. Finally, one-time HCV screening could be considered for the entire adult population.

In this issue of Clinical Infectious Diseases, Coffin et al compare the effectiveness and cost-effectiveness of adding one-time chronic hepatitis C screening of the US population aged 20–69 years to the current risk factor–based approach and also considering one-time screening of only those born between 1945 and 1965 (who have the highest prevalence of hepatitis C) [24]. For this purpose, the authors use a decision-analytic model and available knowledge on the natural history of a disease and treatment efficacy to compare benefits and costs of various interventions and identify those that are most cost effective. When experimentation is not feasible, mathematical modeling, which would extend the time horizon of the usual epidemiological tools (ie, observational cohorts and randomized controlled trials) and evaluate more strategies than possible in a single trial, might be a valuable tool for evaluating alternative interventions and establishing priorities for health interventions. In their study, Coffin et al demonstrate that the addition of one-time screening of the general adult US population for chronic hepatitis C would be cost effective compared with the current practice of screening only high-risk individuals under various scenarios. They also emphasize the fact that screening only high-risk birth cohorts may be more cost effective than screening the general population. The study by Coffin et al is novel because it is one of the rare studies evaluating the cost-effectiveness of one-time HCV testing in adults.

Two other analyses recently evaluated the cost-effectiveness of different HCV screening strategies in the United States, but they both considered only one-time screening of high-risk birth cohorts [25, 26]. Both studies indicated that this strategy was likely to provide substantial health benefits by reducing lifetime cases of advanced liver disease and HCV-related deaths. It would also be cost effective for conventional willingness-to-pay thresholds and should therefore be considered in place of a risk-based screening strategy alone [25].

In light of the results by Coffin et al, should we recommend one-time HCV testing in adults, or should we rather consider one-time screening of high-risk birth cohorts? The results the study by Coffin et al, which require confirmation in other developed-country settings, seem to assign priority to one-time HCV testing of adults from a cost-effectiveness point of view. One-time HCV testing in the general population would be of interest because it could be performed at the same time as HIV testing, which is now recommended in the United States and France [27, 28]. However, issues other than safety, efficacy, and “added value” should be evaluated when considering implementation of new strategies including affordability [29]. In addition to evaluating the cost-effectiveness of new interventions, it is important to assess the financial consequences of introducing a new technology in a specific setting over the short-to-medium term (ie, a budget-impact analysis). Such an analysis, which may favor one-time screening of high-risk birth cohorts because it targets a smaller number of patients, will provide additional information for decision making in a context in which financial resources are scarce.

In the near future, we will probably move toward new HCV testing strategies that expand current recommendations. New strategies should be implemented promptly. Indeed, as stated by Coffin et al, given the peak of the HCV epidemic in the United States, the cost of the public health burden of hepatitis C will substantially increase in the near future, and the window of time available for intervening is limited [24]. By targeting either birth cohorts or the general population, these screening strategies can only be successful if efforts are implemented to increase acceptability of screening by patients and clinicians and improve linkage to care.

Note

Potential conflicts of interest.

S. D.-B. has received unrestricted grants from Roche, Janssen Pharmaceuticals, and Schering-Plough and consultancy honoraria from Merck and GlaxoSmithKline. Y. Y. has received travel grants and honoraria for presentations at workshops and consultancy honoraria from Abbott, Bristol-Myers Squibb, Gilead, Merck, Roche, Tibotec, and ViiV Healthcare.

All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Received December 30, 2011.  Accepted January 6, 2012.

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