Larger belly linked to memory problems in people with HIV

Public release date: 13-Feb-2012

Contact: Rachel Seroka
rseroka@aan.com
651-695-2738
American Academy of Neurology

ST. PAUL, Minn. – A larger waistline may be linked to an increased risk of decreased mental functioning in people infected with the AIDS virus HIV, according to research published in the February 14, 2012, print issue of Neurology®, the medical journal of the American Academy of Neurology.

"Interestingly, bigger waistlines were linked to decreased mental functioning more than was general obesity," said study author J. Allen McCutchan, MD, MSc, of the University of California, San Diego. "This is important because certain anti-HIV drugs cause weight gain in the center of the body that is most dramatic in the abdomen, neck, chest and breasts."

The study was performed in 130 HIV positive people from six clinics. Participants were around the age of 46 with HIV infection for an average of 13 years. Most participants were taking combinations of anti-HIV drugs called antiretroviral therapy. Impaired mental functions such as poor memory and concentration, called neurocognitive impairment (NCI), was diagnosed in 40 percent of study participants.

People with NCI had waist circumferences of an average of 39 inches, compared to 35 inches for those without memory difficulties. NCI was also linked to older age, a longer time living with HIV and diabetes in people older than 55 years. For example, five times as many people with memory problems also had diabetes compared to those with no memory problems (15 percent compared to 3 percent).

"Avoiding those HIV drugs that cause larger waistlines might protect or help to reverse NCI," said McCutchan. "We don't know if central obesity is causing NCI directly or is just a marker for exposure to a more direct cause such as anti-HIV drugs. People with HIV should talk to their doctors before considering changes in their anti-HIV medications."

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The study was supported by the National Institutes of Health.

To learn more about cognitive impairment, visit http://www.aan.com/patients.

The American Academy of Neurology, an association of more than 25,000 neurologists and neuroscience professionals, is dedicated to promoting the highest quality patient-centered neurologic care. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson's disease and epilepsy.

For more information about the American Academy of Neurology, visit http://www.aan.com or find us on Facebook, Twitter, Google+ and YouTube.

Media Contacts:
Rachel Seroka, rseroka@aan.com, (651) 695-2738
Angela Babb, APR, ababb@aan.com, (651) 695-2789

Source

Hepatitis Testing Day – May 19

CDC’s Know More Hepatitis campaign was officially announced on World Hepatitis Day, July 28th, 2011 at a special White House event to release the U.S. Department of Health & Human Services’ Combating the Silent Epidemic of Viral Hepatitis: Action Plan for the Prevention, Care & Treatment of Viral Hepatitis. The plan calls for a national education campaign to educate people about viral hepatitis and encourage people to get tested. As part of this educational initiative, May 19th has been designated as a national “Hepatitis Testing Day” in the United States.

The CDC will use the first ever Hepatitis Testing Day on May 19, 2012 as an opportunity to remind health care providers and the public who should be tested for chronic viral hepatitis. Millions of Americans have chronic viral hepatitis; most of them do not know they are infected.

Resources

HHS Plan

Combating the Silent Epidemic of Viral Hepatitis: Action Plan for the Prevention, Care & Treatment of Viral Hepatitis
http://www.hhs.gov/ash/initiatives/hepatitis/actionplan_viralhepatitis2011.pdf  [PDF - 84 pages]

Chronic Hepatitis B

Resources for Health Professionals
http://www.cdc.gov/hepatitis/HBV/TestingChronic.htm

Patient information about testing
http://www.cdc.gov/hepatitis/HBV/PDFs/HepBAtRisk.pdf   [PDF - 2 pages]

Chronic Hepatitis C

Resources for Health Professionals
http://www.cdc.gov/hepatitis/HCV/Management.htm

Patient information about testing
http://www.cdc.gov/hepatitis/HCV/PDFs/HepCTesting-Diagnosis.pdf   [PDF - 2 pages]

Twitter

Twitter: Follow CDC’s Division of Viral Hepatitis @cdchep.
Share information on Twitter about how you’re taking action for Hepatitis Testing Day, use the hashtag #HTD.

Theme Contest

Theme – submit your ideas for this year’s theme to hepatitis@cdc.gov.

Know More Hepatitis Campaign

Learn more about CDC’s upcoming campaign at
http://www.cdc.gov/hepatitis/KnowMoreHepatitis.htm

Source

Antiviral strategies in hepatitis C virus infection

J Hepatol. 2012;56 Suppl:S88-S100.

Sarrazin C, Hézode C, Zeuzem S, Pawlotsky JM.

Klinikum der J.W. Goethe-Universität, Medizinische Klinik 1, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.

Abstract

Resolution of the three-dimensional structures of several hepatitis C virus (HCV) proteins, together with the development of replicative cell culture systems, has led to the identification of a number of potential targets for direct-acting antiviral (DAA) agents. Numerous families of drugs that potently inhibit the HCV lifecycle in vitro have been identified, and some of these molecules have reached early to late clinical development. Two NS3/4A protease inhibitors, telaprevir and boceprevir, were approved in Europe and the United States in 2011 in combination with pegylated interferon (IFN)-α and ribavirin for the treatment of chronic hepatitis C related to HCV genotype 1, in both treatment-naïve and treatment-experienced patients. Sustained virological response rates in the range of 6675% and 5966% (2988% if the response to the first course of therapy is taken into account) have been achieved in these two patient populations, respectively, with treatment durations of 24 to 48 weeks. A number of other DAAs are at the clinical developmental stage in combination with pegylated IFN-α and ribavirin or with other DAAs in IFN-free regimens, with or without ribavirin. They include second-wave, first-generation, and second-generation NS3/4A protease inhibitors, nucleoside/nucleotide analogue inhibitors and non-nucleoside inhibitorsof HCVRNA-dependent RNA polymerase, inhibitors of nonstructural protein 5A (NS5A) and host-targeted compounds, such as cyclophilin inhibitors and silibinin. The proof of concept that IFN-free regimens may lead to HCV eradication has recently been brought. However, new drugs may be associated with troublesome side effects and drugdrug interactions, and the ideal IFN-free DAA combination remains to be found.

Source

A Phase 1, Randomized, Placebo-Controlled, Three-Day, Dose-Ranging Study of GS-5885, an NS5A Inhibitor, in Patients with Genotype 1 Hepatitis C.

J Hepatol. 2012 Feb 4. [Epub ahead of print]

Lawitz EJ, Gruener D, Hill JM, Marbury T, Moorehead L, Mathias A, Cheng G, Link JO, Wong KA, Mo H, McHutchison JG, Brainard DM.

Alamo Medical Research, San Antonio, Texas.

Abstract

BACKGROUND & AIMS: GS-5885 is an inhibitor of the hepatitis C virus (HCV) NS5A protein and exhibits potent suppression of genotype 1 HCV replicons. The safety, tolerability, pharmacokinetics, antiviral activity, and resistance profile of once-daily GS-5885 doses of 1-90 mg were evaluated in patients with chronic genotype 1 HCV.

METHODS: Genotype 1 HCV-infected patients were randomized to 3 days of once-daily (QD) dosing with placebo (n=12) or GS-5885 1 mg (n=10), 3 mg (n=10), 10 mg (n=20), 30 mg (n=10), or 90 mg (n=10). Plasma samples for pharmacokinetics, HCV RNA, and NS5A sequencing were collected through Day 14.

RESULTS: GS-5885 was well tolerated and resulted in median maximal reductions in HCV RNA ranging from 2.3 log(10) IU/mL (1 mg QD) to 3.3 log(10) IU/mL (10 mg QD in genotype 1b and 30 mg QD). E(max) modeling indicated GS-5885 30 mg was associated with >95% of maximal antiviral response to HCV genotype 1a. HCV RNA reductions were generally more sustained among patients with genotype 1b versus 1a. Three of 60 patients had a reduced response and harbored NS5A-resistant virus at baseline. NS5A sequencing identified residues 30 and 31 in genotype 1a, and 93 in genotype 1b as the predominant sites of mutation following GS-5885 dosing. Plasma pharmacokinetics were consistent with QD dosing.

CONCLUSIONS: During 3 days of monotherapy, low doses of GS-5885 demonstrated significant antiviral activity in genotype 1a and 1b HCV-infected patients. GS-5885 is currently being evaluated in combination direct antiviral regimens with and without peginterferon.

Source

New research reveals how protein protects cells from HIV infection

Public release date: 12-Feb-2012

Contact: Jessica Guenzel
jessica.guenzel@nyumc.org
212-404-3591
NYU Langone Medical Center / New York University School of Medicine

Finding offers potential new drug targets aimed at slowing progression of disease

NEW YORK -- A novel discovery by researchers at NYU Langone Medical Center and colleagues reveals a mechanism by which the immune system tries to halt the spread of HIV. Harnessing this mechanism may open up new paths for therapeutic research aimed at slowing the virus' progression to AIDS. The study appears online ahead of print today in Nature Immunology.

"A lot of research on viruses, especially HIV, is aimed at trying to understand what the body's mechanisms of resistance are and then to understand how the virus has gotten around these mechanisms," said co-lead investigator Nathaniel R. Landau, PhD, a professor of microbiology at the Joan and Joel Smilow Research Center at NYU School of Medicine.

The research focused on a protein called SAMHD1. Recent studies have found that immune cells, called dendritic cells, containing the protein are resistant to infection by HIV. Since the discovery, scientists have sought to understand how SAMHD1 works to protect these cells, with hopes that science might find a way to synthetically apply that protection to other cells.

Dr. Landau and his team are now able to provide an answer:

When a virus, like HIV, infects a cell, it hijacks the cell's molecular material to replicate. That molecular material is in the form of deoxynucleotide triphosphates (dNTPs), which are the building blocks for DNA. Once the virus replicates, the resulting DNA molecule contains all the genes of the virus and instructs the cell to make more virus.

Researchers wanted to understand how cells containing the SAMHD1 protein are protected from such hijacking. They found that SAMHD1 protects the cell from viruses by destroying the pool of dNTPs, leaving the virus without any building blocks to make its genetic information – a process researchers call nucleotide pool depletion. "SAMHD1 essentially starves the virus," Dr. Landau said. "The virus enters the cell and then nothing happens. It has nothing to build and replicate with, so no DNA is made."

As a result, the most common form of HIV does not readily infect these cells. Instead, the virus has evolved to replicate mainly in a different kind of cell, called CD4 T-cells, which do not contain SAMHD1 and therefore have a healthy pool of dNTPs. Dr. Landau explained that the virus has evolved in such a way that it may deliberately avoid trying to infect immune cells with SAMHD1 to avoid alerting the greater immune system to activate a variety of antiviral mechanisms to attack the virus. Viruses that are related to HIV, like HIV-2 and SIV, have developed a protein called viral protein X (VPX) that directly attacks SAMHD1. This allows the virus to infect dendritic cells, an important type of immune cell.

"Viruses are remarkably clever about evading our immune defenses," Dr. Landau said. "They can evolve quickly and have developed ways to get around the systems we naturally have in place to protect us. It's a bit of evolutionary warfare and the viruses, unfortunately, usually win. We want to understand how the enemy fights so that we can outsmart it in the end."

Understanding the mechanism by which SAMHD1 provides protection to cells may provide a new idea about how to stop or slow the virus' ability to spread, Dr. Landau explained. Potential future research efforts, for example, might focus on finding a way to increase the amount of SAMHD1 in cells where it does not exist, or to reduce the amount of dNTPs in cells vulnerable to infection.

"Over the past few years, a number of these natural resistance mechanisms have been identified, specifically in HIV, but some have potential applications to other viruses, as well," he said. "This is a very exciting time in HIV research. Many of the virus' secrets are being revealed through molecular biology, and we're learning a tremendous amount about how our immune system works through the study of HIV."

###

Funded in part by the National Institutes of Health and the American Foundation for AIDS Research, the study was conducted in collaboration with researchers at several institutions, including the University of Rochester Medical Center and The Cochin Institute, in Paris.

About NYU School of Medicine:

NYU School of Medicine is one of the nation's preeminent academic institutions dedicated to achieving world class medical educational excellence. For 170 years, NYU School of Medicine has trained thousands of physicians and scientists who have helped to shape the course of medical history and enrich the lives of countless people. An integral part of NYU Langone Medical Center, the School of Medicine at its core is committed to improving the human condition through medical education, scientific research and direct patient care. The School also maintains academic affiliations with area hospitals, including Bellevue Hospital, one of the nation's finest municipal hospitals where its students, residents and faculty provide the clinical and emergency care to New York City's diverse population, which enhances the scope and quality of their medical education and training. Additional information about the NYU School of Medicine is available at http://school.med.nyu.edu/

Source

Management of treatment failure in chronic hepatitis B

J Hepatol. 2012;56 Suppl:S112-22.

Zoulim F, Locarnini S.

INSERM, U1052, Cancer Research Center of Lyon, 69003 Lyon, France; Université de Lyon, 69003 Lyon, France; Hospices Civils de Lyon, Hepatology Department, 69004 Lyon, France; Institut Universitaire de France.

Abstract

Antiviral therapy of chronic hepatitis B remains a clinical challenge. The primary goal of therapy is to prevent liver disease progression. Because of the mechanism of viral persistence in infected hepatocytes, long-term antiviral therapy is needed in the majority of patients. Incomplete viral suppression and emergence of drug resistance is a major concern. The correct choice of a first-line potent therapy to achieve sustained long-term suppression of viral replication provides the best chance of preventing treatment failure and drug resistance. Clinical studies have demonstrated that drugs with a high barrier to resistance, such as entecavir and tenofovir, have significantly lower rates of resistance when compared with those with a low barrier to resistance such as lamivudine, adefovir, or telbivudine. Management of treatment failure requires a precise clinical and accurate virologic monitoring as well as an early treatment intervention with appropriate complementary drugs with respect to their cross-resistance profile. Long-term surveillance for treatment efficacy and possible emergence of drug resistance is necessary for those patients who have been sequentially treated with multiple antivirals. Finally, the identification of novel treatment targets remains a major research challenge to improve the efficacy of current antiviral therapy.

Source

Interferon and Ribavirin Control HCV Genotype 6

From Reuters Health Information

By David Douglas

NEW YORK (Reuters Health) Feb 08 - Pegylated interferon and ribavirin are effective against chronic infection with hepatitis C virus (HCV) genotype 6, a recent study shows.

"This large randomized study provides new information on treatment of genotype 6 patients, particularly on shortening duration of therapy in select patients (and) thus limiting costs of an expensive treatment," said Dr. K. Rajender Reddy of the University of Pennsylvania, Philadelphia in an email to Reuters Health.

Genotype 6 (which now includes genotypes 7, 8 and 9) is endemic in Southeast Asia, where it accounts for up to 47% of HCV infections. Once problematic mainly in that part of the world, "in the changing era of increasing migration of populations, it has been recently reported in the United States, as well as in China, Taiwan, and Hong Kong," Dr. Reddy and colleagues wrote in a paper online January 17 in the Journal of Hepatology.

The interferon/ribavirin combination is the standard treatment for HCV, but genotype is considered to be a strong predictor of sustained virological response (SVR) and little is known about response and optimal treatment duration with genotype 6, the investigators say.

The new trial included 105 treatment-na�ve HCV genotype 6 patients in Vietnam who were randomized to 24 or 48 weeks of treatment with pegylated interferon alfa-2a 180 mcg per week and ribavirin 15 mg/kg per day.

The study was not funded, and the patients had to pay for their care. Six dropped out for economic reasons and another seven were lost to follow-up.

Even so, on intention-to-treat analysis the SVR was 60% in the 24-week group and 71% in the 48-week group. The difference was not significant. Corresponding biochemical responses were 63% and 77%.

Rates of virological relapse were 7% with the shorter course of treatment and 5% with the longer course.

Overall, SVR was most likely in those with a rapid virological response. In the 24-week group, 75% of such patients achieved SVR. In the 48-week group, the proportion was 86%.

Rates of hematologic and general adverse events were similar between the two groups, except the rate of anemia was lower with shorter treatment (31% vs 57%).

According to the paper, "24 weeks of therapy in younger patients, with low viral load and rapid virological response appeared equally effective as 48 weeks of therapy and this is likely to have a major economic impact on HCV therapy, in such subpopulations."

In fact, Dr. Reddy noted that the efficacy of shorter-duration therapy is scientifically worth pursuing in larger trials, but given the lack of support for the current study, "challenges are in funding."

"While new drugs are being developed for non-genotype 6 hepatitis C infections," he concluded, "pegylated interferon and ribavirin will remain the standard of care for the foreseeable future for genotype 6 infections."

Source: http://bit.ly/zJBkoU

J Hepatol 2012.

Source

Hershey AIDS Discrimination: AHF Launches Valentine's 'A Day without Kisses' Boycott

PRESS RELEASE

Feb. 10, 2012, 5:00 p.m. EST

AIDS advocates call on public with e-letter campaign and call for Valentine boycott of Hershey chocolates over Milton Hershey School's rejection of a 13-year-old boy due to his HIV-positive status

LOS ANGELES, Feb 10, 2012 (BUSINESS WIRE) -- --Advocates for the "Hershey: A Day without Kisses" demand that Hershey -- which funds the school -- denounce the discrimination and permit the boy's enrollment

AIDS Healthcare Foundation (AHF) announced today that it is spearheading a nationwide 'Hershey: A Day without Kisses' Valentine Day's boycott of the Hershey Company over the Milton Hershey School's AIDS discrimination. The Milton Hershey School -- a prestigious boarding school for low-income scholarship students funded by the Hershey Company -- recently rejected a 13-year-old boy for admission citing his HIV-positive status as the reason, misguidedly calling him a "direct threat to the health and safety of others." The group formally launched its action via Facebook, Twitter and other online media today as part of its ongoing 'No Kisses for Hershey' campaign. AHF and AIDS advocates are now calling on the public to forgo buying all Hershey candy and chocolates this Valentine's Day.

On Tuesday, February 14th, AHF and AIDS advocates in Los Angeles will also host a press conference and teleconference about its call on the public to forgo buying Hershey candy and chocolates this Valentine's Day. The group formally launched its action via Facebook, Twitter and other online media today as part of its ongoing 'No Kisses for Hershey' campaign.

The group previously launched the website www.EndHIVStigma.org where the public can learn more about the case, learn the facts about HIV/AIDS and send e-letters to three Hershey Company board members who also sit on the board of the Milton Hershey School Trust, urging them to denounce the discrimination and facilitate the boy's admission into the school.

"We are asking the public to join us in telling Hershey that this Valentine's Day will be 'A Day without Kisses' for them as Hershey continues on its path of discrimination and ignorance as displayed by the Hershey School's recent rejection of an otherwise qualified student due to his HIV-positive status," said Michael Weinstein, President of AIDS Healthcare Foundation in a statement from Africa. "Ultimately, it is the Hershey Company itself, as the main funder of the school, that must answer for the decision not to admit the boy -- a decision fueled by prejudice and fear. Hershey must denounce this illegal and repugnant discrimination and enroll the boy at the school. In the meanwhile, we plan to use the power of pocketbook to shame Hershey by asking fair-minded members of the chocolate-buying public not to buy Hershey this Valentine's Day."

Shortly after news broke just before World AIDS Day, December 1, 2011, about the school's rejection of the HIV-positive boy, AIDS Healthcare Foundation hosted a press conference in Washington, D.C., to announce the launch of a campaign against HIV/AIDS discrimination at Hershey School in Pennsylvania and in support of the federal discrimination lawsuit filed on behalf of a 13-year-old boy who was rejected for admission at Hershey explicitly due to his HIV-positive status. At the event, AHF announced its willingness to contribute up to $50,000 to support a lawsuit filed by AIDS Law Project of Pennsylvania on behalf of the boy and expressed its moral outrage at the case.

According to the Associated Press (claim:Hershey School Rejects HIV-Positive Pa. Boy)(claim:By Peter Jackson)(claim:12/1/11): "A private boarding school connected with the Hershey chocolate company says it was trying to protect other students when it denied admission to a Philadelphia-area teenager because he is HIV-positive. The AIDS Law Project of Pennsylvania filed a lawsuit on behalf of the unidentified boy in U.S. District Court in Philadelphia on Wednesday, claiming the Milton Hershey School for disadvantaged students violated the Americans with Disabilities Act. School officials acknowledged that the 13-year-old boy was denied admission because of his medical condition. They said they believed it was necessary to protect the health and safety of the 1,850 others enrolled in the residential institution, which serves children in pre-kindergarten to 12th grade and where students live in homes with 10 to 12 others."

"The ignorance displayed by the Hershey School's leadership is unacceptable and demonstrates just how much work there is still to be done to dismantle the fear and misinformation that still surrounds this disease more than 25 years after Ryan White," added AHF's Weinstein.

Ryan White was an American teenager from Kokomo, Indiana who, in the mid-1980s, was expelled from middle school because he was HIV-positive. A lengthy legal battle with the school ensued and White became a galvanizing force in educating the country about HIV & AIDS at a time when misinformation about the disease was widespread. After his death in 1990, the U.S. Congress passed a major piece of legislation named in his honor, the Ryan White CARE Act, which provides funding for HIV/AIDS programs for low-income American.

"It is unfortunate that Hershey has shown such a shocking lack of knowledge of basic facts about HIV and how it is spread, and are instead reacting with ignorance and prejudice," said Tom Myers, General Counsel and Chief of Public Affairs for AIDS Healthcare Foundation. "This is an excellent opportunity to educate the public about HIV, including the fact that people who are living with HIV/AIDS do not pose a significant risk to others and generally do not require any special medical attention that cannot be obtained through normal medical visits."

He/she added: "In addition, people should know that recent studies have shown that people with HIV on treatment are up to 96% non-infectious. Because of this, those on treatment are not a threat to health and safety of others. The young man in question does not pose a 'direct threat' to anyone and Hershey should admit him into the school to begin the education that he desires -- and deserves."

AIDS Healthcare Foundation (AHF), the largest global AIDS organization, currently provides medical care and/or services to more than 125,000 individuals in 26 countries worldwide in the US, Africa, Latin America/Caribbean, the Asia/Pacific Region and Eastern Europe. To learn more about AHF, please visit our website: www.aidshealth.org , find us on Facebook: www.facebook.com/aidshealth and follow us on Twitter: @aidshealthcare.

        
WHAT:    PRESS CONFERENCE -- update on HERSHEY COMPANY VALENTINE BOYCOTT targets AIDS discrimination at Milton Hershey School

WHEN:    Tuesday, February 14th, 10:00 a.m(Pacific)

WHERE:   AIDS Healthcare Foundation Headquarters
6255 Sunset Blvd., Suite 2100 (cross street:Argyle) Hollywood, CA 90028
 
www.EndHIVStigma.org            

NOTE:    TELECON to follow 10:30 a.m. -- Dial in +1-877-411-9748 participant code #7931503

Making History: Eliminating Viral Hepatitis Disparities in the African American Community

February 10, 2012

By J. Nadine Gracia, MD, MSCE, Acting Director, Office of Minority Health, U.S. Department of Health and Human Services

Dr. J. Nadine Gracia

During February’s observance of African American History Month, please join us in working to end the unfortunate history of viral hepatitis’ disproportionate impact on the African American community. This Administration is working hard to reduce and eliminate health disparities and achieve health equity.

Unfortunately, viral hepatitis is a health problem that is often overlooked by the public as well as healthcare providers. This, despite the fact that viral hepatitis is a leading infectious cause of death, claiming the lives of 12,000–15,000 Americans each year. As many as 5.3 million Americans are living with viral hepatitis, though most do not know that they are infected. This places them at greater risk for severe, even fatal, complications from the disease and increases the likelihood that they will spread the virus to others.

What Is Hepatitis?
“Hepatitis” means inflammation of the liver. It is most often caused by a virus. In the U.S., the most common types are hepatitis A, hepatitis B, and hepatitis C. All of these viruses cause acute, or short-term, viral hepatitis. But the hepatitis B and C viruses (HBV and HCV) can also cause chronic hepatitis, in which the infection is prolonged, sometimes lifelong. Chronic hepatitis can lead to cirrhosis, liver failure, and liver cancer. In fact, viral hepatitis is the leading cause of liver cancer and the most common reason for liver transplantation.

Viral Hepatitis Disparities
Within the African American community, significant hepatitis-related health disparities exist. For example:

Hepatitis B

• Hepatitis B can be prevented by a vaccine; however, African American children have lower HBV vaccination rates than non-Hispanic white children.
• Since 2004, rates of hepatitis B have remained steady among all racial/ethnic populations. However, new infections of hepatitis B remain the highest among African Americans, with 2.3 cases per 100,000 people.

Hepatitis C

• African Americans are twice as likely to be infected with hepatitis C when compared with the general U.S. population and chronic liver disease, often hepatitis C-related, is a leading cause of death among African Americans ages 45-64.
• While African Americans represent only 12% of the U.S. population, they make up about 22% of the chronic hepatitis C cases. In fact, African Americans have a substantially higher rate of chronic hepatitis C infection than do Caucasians and other ethnic groups.

Viral Hepatitis Action Plan
My Federal colleagues and I are committed to ensuring that new cases of viral hepatitis are prevented and that persons who are already infected are tested; informed about their infection; and provided with counseling, care, and treatment. In fact, last year we issued Combating the Silent Epidemic of Viral Hepatitis: Action Plan for the Prevention, Care & Treatment of Viral Hepatitis (PDF 672KB), which outlined robust and dynamic steps that are now underway across the government to increase viral hepatitis awareness and knowledge among health care providers and communities, and improve access to quality prevention, care, and treatment services for viral hepatitis. (Read more about the Action Plan.)

In addition, the Viral Hepatitis Action Plan is both supported by and complements several other initiatives unfolding within HHS and across the Federal government, including the:

• The National HIV/AIDS Strategy, which helps us address the significant rates of HIV-HCV coinfection;
• The National Prevention Strategy, which calls for us to enhance early detection of HIV, viral hepatitis, and other sexually transmitted infections and improve linkage to care;
• The U.S. National Vaccine Plan, which will help us reduce the incidence of vaccine-preventable hepatitis A and B;
• The HHS Action Plan to Reduce Racial and Ethnic Health Disparities; and
• The infectious disease and immunization objectives of Healthy People 2020, which specifically seek to reduce new hepatitis A, B, and C infections and increase viral hepatitis awareness among infected persons.

Your Help Is Essential
These are all part of our response to the silent epidemic of viral hepatitis. But we need your help, too. So, during African American History Month, please help by learning more about viral hepatitis, educating family and friends about this silent killer in the African American community, and encouraging conversations with healthcare providers about vaccinations for hepatitis A and B and screening for hepatitis C for those who may have been exposed.

Together, we can make viral hepatitis history.

Source

Tenofovir: Q&A for Patients and Providers

February 10, 2012

Scientists at the San Francisco VA Medical Center and the University of California, San Francisco have published a study showing that one of the most effective and commonly prescribed antiretroviral medications for HIV/AIDS, tenofovir, is associated with a significant risk of kidney damage and chronic kidney disease that increases over time. See accompanying news release, Tenofovir, Leading HIV Medication, Linked with Risk of Kidney Damage.

What is the new finding about HIV/AIDS drugs and associated kidney problems?

Tenofovir, an anti-retroviral drug used to treat HIV, was associated with an increased risk of kidney disease in an observational study of 10,841 HIV-infected veterans who were new users of antiretroviral therapy between 1997 and 2007. The study found that tenofovir is associated with an elevated risk of kidney disease, even in persons without pre-existing risk factors for kidney disease, and that this toxicity to the kidney may not be reversible.

The study showed that for each year that a person uses tenofovir, there is a 34 percent higher risk of developing protein in the urine, which is an important sign of kidney damage; an 11% higher risk of rapidly declining kidney function, and a 33% higher risk of developing chronic kidney disease. These risks are all independent of the other factors that cause kidney disease, such as age, diabetes, hypertension, smoking, hepatitis C infection and HIV-related factors.

How much extra risk is this?

Overall in the study, the differences in risk between users and non-users of tenofovir each year were: 13% vs. 8% for protein in urine, which is an important marker of kidney damage 9% vs. 5% for rapidly declining kidney function; and 2% vs. 1% for developing chronic kidney disease. However, these numbers are based on the average risks in the study population, and patients with more risk factors for kidney disease would be put at proportionately higher risk when they use tenofovir.

Which drugs are we talking about?

In the study, the risk appeared to be unique to tenofovir. Other antiretroviral drugs showed weaker or inconsistent associations with kidney disease events, and none was associated with higher risk for even two of these three adverse kidney disease outcomes.

Should I stop taking these drugs if I am already taking them now?

This decision should be made on an individual basis, in consultation with your physician. The decision should involve weighing the risks/benefits and discussion of alternative treatment options. Tenofovir is an important component of effective antiretroviral therapy that you may need to control your viral load. If you remain on tenofovir, you may need more frequent monitoring of your kidney function and your level of urine protein. You are likely at increased risk of kidney disease if you have diabetes, high blood pressure, cardiovascular disease or hepatitis C. African Americans, Hispanics, Pacific Islanders, Native Americans and older adults are also at increased risk.

What are the symptoms of kidney problems? Should I be taking tests to monitor my kidney function?

Most people do not have any symptoms until their kidney disease is advanced. So, kidney disease is typically detected by screening tests of blood and urine.

Moving forward, what questions should I ask my doctors?

You should ask your doctor about whether you need routine monitoring of blood and urine samples to measure the following: serum creatinine, proteinuria, and microalbuminuria. You should also ask your doctor to calculate your estimated glomerular filtration rate (eGFR). You may want to have a discussion about alternative treatment options.

What about the prophylactic use of these drugs to prevent HIV progression and transmission?

A study of HIV pre-exposure prophylaxis (PrEP) using once-daily oral tenofovir was presented at the XVIII International Conference on AIDS (AIDS 2010), which included 323 men. This study found no indication of significant safety issues, including kidney problems or bone loss. However, this study may not have been large enough to detect increases in risk for kidney disease.

Where can I get more information?

You may get more information from HIV/AIDS websites such as Project Inform or HIV InSite. You can also contact your doctor if you have additional questions about your anti-retroviral medications or risk for kidney disease.

Source

How Reliable is Hepatitis B Vaccination in People Celiac Disease?

By Jefferson Adams Published 02/10/2012

Celiac.com 02/10/2012 - The HBV vaccine is usually effective against common hepatitis B virus (HBV) infection, with just 4-10% of vaccine recipients failing to respond to standard immunization. Some studies suggest that people with celiac disease may have high levels of resistance to the HBV vaccine, compared to the general population.

A team of researchers recently took a look at the issue of HBV vaccine reliability in people with celiac disease.

The study team included Mohammad Rostami Nejad, Kamran Rostami, and Mohammad Reza Zali. They are variously affiliated with the Research Center for Gastroenterology and Liver Disease at Shahid Beheshti University of Medical Sciences in Tehran, Iran, and with Acute Medicine at Dudley Group of Hospital in Dudley, UK. Together, they reviewed data from previous studies.

The ability to respond to recombinant HBV vaccine is associated with certain gene sites. At those sites, certain HLA haplotypes, such as B8, DR3, and DQ2 are common genetic markers among non-responders.

Since HLA genotypes play an important role in unresponsiveness to the HBV vaccine, and since 90-95% of people with celiac disease have HLA-DQ2, celiac disease may be a factor in this failure to respond to the HBV vaccine.

For one study, Ertekin et al., a research team gave HBV vaccinations, according to a standard immunization schedule, to 52 children with celiac disease, and another twenty matched for age and sex.

The average age of the celiac disease patients was 10.7 ± 4 years (range, 4-18 years). Anti-HBs titers were positive in 32 (61.5%) patients and negative in 20 (38.5%) patients, while they were positive in 18 (90%) of the children in the control group (P < 0.05).

The review team found statistically significant differences between negative anti-HBs titers, clinical presentation of CD, and dietary compliance in patients with CD (P < 0.05).
In all, 32 of the 52 children with celiac disease responded favorably to HBV vaccination. This was a substantially lower percentage that the 18 of 20 control subjects responded (P < 0.05).

Ertekin et al. concluded that a significantly higher percentage of children with celiac disease failed to respond to hepatitis B vaccination, as compared with the control group.

They concluded that response to the HBV vaccine in children with celiac disease should be investigated, and a different immunization schedule should be developed for them. They suggested that celiac children who follow a gluten-free diet may have a better immune response to the HBV vaccine.

The data fits with previous studies that confirm the findings that children with celiac disease fail to respond to the HBV vaccine at significantly higher rates than do healthy children.

In fact, the researchers point out a similar study on adults, Noh et al., revealed that, of 23 adults with celiac disease who had completed a full course of HBV vaccination, 19 tested positive for HBsAb and 13 failed to acquire proper long-term immunity.

Another study, by Stachowski et al., further cemented this connection between HLA and non-responsiveness to HBV vaccine. In that study, 34 out of 153 patients with end-stage renal disease failed to respond to HBV vaccine, and HLA-DQ2 was found almost exclusively in the non-responder group.

Long stretches of time between vaccination and antibody testing might be one reason even celiac disease patients who follow a gluten-free diet have significantly reduced post-vaccination levels of HBV antibody. Therefore, current guidelines recommend revaccinating celiac patients once they have established a reliable gluten-free diet.

This study was not designed to assess the presence of HLA-DQ2 and HLA-DQ8 in the groups. Therefore, future studies assessing HLA haplotypes in celiac disease should seek to describe the role of HLA typing in response to HBV vaccination.

The evidence indicates that early diagnosis of celiac disease, and treatment with a gluten-free diet may increase the overall percentage of patients responding favorably to the HBV vaccine.

Treatment of celiac disease with a strict, gluten-free diet seems to play a positive role in the development of antibody memory.

The review team points out that the high prevalence of celiac disease in the general population and a lack of response to HBV vaccine in untreated patients, invites routine assessment in patients with celiac disease receiving the HBV vaccine.

Lastly, the review team notes that non-responsiveness to HBV vaccine may indicate undiagnosed celiac disease or noncompliance with gluten-free diet.

SOURCE:
Hepat Mon. 2011 August 1; 11(8): 597–598.
doi: 10.5812/kowsar.1735143X.761

Source

New Molecule Has Potential to Help Treat Genetic Diseases and HIV

Chemists at The University of Texas at Austin have synthesized a molecule that can entangle itself in a specific sequence of DNA and stay attached for 16 days, longer than any other molecule reported.

Feb. 10, 2012

AUSTIN, Texas — Chemists at The University of Texas at Austin have created a molecule that's so good at tangling itself inside the double helix of a DNA sequence that it can stay there for up to 16 days before the DNA liberates itself, much longer than any other molecule reported.

It's an important step along the path to someday creating drugs that can go after rogue DNA directly. Such drugs would be revolutionary in the treatment of genetic diseases, cancer or retroviruses such as HIV, which incorporate viral DNA directly into the body's DNA.

"If you think of DNA as a spiral staircase," says Brent Iverson, professor of chemistry and chair of the department of chemistry and biochemistry, "imagine sliding something between the steps. That's what our molecule does. It can be visualized as binding to DNA in the same way a snake might climb a ladder. It goes back and forth through the central staircase with sections of it between the steps. Once in, it takes a long time to get loose."

Iverson says the goal is to be able to directly turn on or off a particular sequence of genes.

"Take HIV, for example," he says. "We want to be able to track it to wherever it is in the chromosome and just sit on it and keep it quiet. Right now we treat HIV at a much later stage with drugs such as the protease inhibitors, but at the end of the day, the HIV DNA is still there. This would be a way to silence that stuff at its source."

Iverson, whose results were published in September in Nature Chemistry, strongly cautions that there are numerous obstacles to overcome before such treatments could become available.

The hypothetical drug would have to be able to get into cells and hunt down a long and specific DNA sequence in the right region of our genome. It would have to be able to bind to that sequence and stay there long enough to be therapeutically meaningful.

"Those are the big hurdles, but we jumped over two of them," says Iverson. "I'll give presentations in which I begin by asking: Can DNA be a highly specific drug target? When I start, a lot of the scientists in the audience think it's a ridiculous question. By the time I'm done, and I've shown them what we can do, it's not so ridiculous anymore."

In order to synthesize their binding molecule, Iverson and his colleagues begin with the base molecule naphthalenetetracarboxylic diimide (NDI). It's a molecule that Iverson's lab has been studying for more than a decade.

They then piece NDI units together like a chain of tinker toys.

"It's pretty simple for us to make," says Amy Rhoden Smith, a doctoral student in Iverson's lab and co-author on the paper. "We are able to grow the chain of NDIs from special resin beads. We run reactions right on the beads, attach pieces in the proper order and keep growing the molecules until we are ready to cleave them off. It's mostly automated at this point."

Rhoden Smith says that the modular nature of these NDI chains, and the ease of assembly, should help enormously as they work toward developing molecules that bind to longer and more biologically significant DNA sequences.

"The larger molecule is composed of little pieces that bind to short segments of DNA, kind of like the way Legos fit together," she says. "The little pieces can bind different sequences, and we can put them together in different ways. We can put the Legos in a different arrangement. Then we scan for sequences that they'll bind."

Iverson and Rhoden Smith's co-authors on the paper were Maha Zewail-Foote, a visiting scientist in Iverson's lab who's now an associate professor and chairman of chemistry at Southwestern University in Georgetown; Garen Holman, another former doctoral student of Iverson's who did most of the experimental work before obtaining his Ph.D.; and Kenneth Johnson, the Roger J. Williams Centennial Professor in Biochemistry at The University of Texas at Austin.

For more information, contact: Daniel Oppenheimer, College of Natural Sciences, 512 232 0682; Brent Iverson, 512-471-5053

Source

FDA sets draft rules for biotech drug copies

By Deena Beasley

Thu Feb 9, 2012 4:46pm EST

(Reuters) - The Food and Drug Administration's long-awaited guidelines for the sale of lower-cost versions of biotechnology drugs leave open the possibility that some products might not need to be tested in humans.

The proposed rules, issued on Thursday, require studies showing that the generic copies are "highly similar" to the originals, but there are several ways that might be proven.

Because of their complexity, generic copies of biotech drugs - first introduced in the 1980s - are known as "biosimilars."

"We're trying to send the signal that it's not one-size-fits-all. It's product-by-product," Rachel Sherman, director of the FDA's office of medical policy, said during a conference call with reporters.

The worldwide market for copies of biotech medicines will grow to $3.7 billion by 2015, from just $243 million in 2010, as more than 30 branded biologics with sales of $51 billion lose patent exclusivity, according to market analysis firm Datamonitor.

The FDA rules would set "an abbreviated pathway" to approval that would consider factors including a product's complexity, formulation and stability, the agency said.

The proposal "reads largely as we expected, although a few points read as slightly more friendly to the generics industry," ISI Group analyst Mark Schoenebaum said in a note to clients.

The FDA said it would decide on the "extent and scope of animal and clinical studies" needed for approval once it has considered other analytical data. The agency said it has yet to receive an application for a biosimilar drug, but nine applications have been filed for clinical trials.

Manufacturers will have the option of asking the FDA to deem their copies "interchangeable" with a brand-name drug, but the `agency said that would require additional clinical studies.

Makers of branded biotech drugs have argued that full-scale human trials need to be conducted before a rival version of an existing biologic drug should be allowed on the market.

Despite such qualms, biotech drug makers including Amgen Inc, Merck & Co and Biogen Idec are working to produce rival versions of biotech drugs made by competitors.

"While the documents provide a roadmap, they are sufficiently vague as to give FDA leeway for case by case assessments of each proposed biosimilar along their respective development paths," said Wells Fargo analyst Brian Abrahams.

The Congressional Budget Office has estimated that the United States could save $25 billion from the use of biosimilars over 10 years.

European regulators have already approved cheaper versions of some biotech drugs.

The FDA said advances in science and manufacturing may facilitate fingerprint-like analysis of therapeutic protein products, which may allow for a more selective approach to any animal or human studies.

Unlike conventional, easy-to-replicate, chemical-based drug compounds, biotech drugs are derived from living organisms, such as proteins, and are often produced using recombinant DNA technologies.

Once a traditional pill loses patent protection, there is a quick regulatory pathway for generic drugmakers to sell much cheaper versions of the branded medicine. Similar U.S. guidelines for biotech drugs have been under negotiation for several years.

Biosimilar drugs are expected to sell at discounts of 25 to 45 percent to branded rivals, compared with generic versions of traditional pills that often sell for one-tenth the price of the branded product.

Under the U.S. healthcare reform law passed in 2010, brand-name biotech drugs - ranging from relatively simple molecules like insulin to complex antibodies used to treat cancer - were granted a 12-year period of market exclusivity, after which generic versions can be sold.

Opposing trade groups - the Biotechnology Industry Organization and the Generic Pharmaceutical Association - said they are reviewing the proposed rules.

The generic drugs group said it was pleased with the FDA's action, which it called "an important step in getting these affordable, lifesaving medicines into the hands of doctors and patients."

The FDA will require that biosimilar manufacturers provide a post-marketing safety monitoring program, which in some cases may include long-term clinical studies.

The agency is accepting public comment on the draft guidance documents for the next 60 days.

(Reporting by Deena Beasley in Los Angeles, Additional reporting by Bill Berkrot in New York and Anna Yukhananov in Washington; Editing by Gerald E. McCormick, John Wallace and Matthew Lewis)

Source

New mental health manual is "dangerous" say experts

By Kate Kelland, Health and Science Correspondent

LONDON | Thu Feb 9, 2012 2:24pm EST

LONDON (Reuters) - Millions of healthy people - including shy or defiant children, grieving relatives and people with fetishes - may be wrongly labeled mentally ill by a new international diagnostic manual, specialists said on Thursday.

In a damning analysis of an upcoming revision of the influential Diagnostic and Statistical Manual of Mental Disorders (DSM), psychologists, psychiatrists and other experts said new categories of mental illness identified in the book were at best "silly" and at worst "worrying and dangerous."

"Many people who are shy, bereaved, eccentric, or have unconventional romantic lives will suddenly find themselves labeled as mentally ill," said Peter Kinderman, head of Liverpool University's Institute of Psychology at a briefing in London about widespread concerns over the manual.

"It's not humane, it's not scientific, and it won't help decide what help a person needs."

The DSM is published by the American Psychiatric Association (APA) and has symptoms and other criteria for diagnosing mental disorders. It is used internationally and seen as the diagnostic "bible" for mental health medicine.

No one from the APA was immediately available for comment.

More than 11,000 health professionals have already signed a petition (at dsm5-reform.com) calling for the development of the fifth edition of the manual to be halted and re-thought.

Some diagnoses - for conditions like "oppositional defiant disorder" and "apathy syndrome" - risk devaluing the seriousness of mental illness and medical zing behaviors most people would consider normal or just mildly eccentric, the experts said.

At the other end of the spectrum, the new DSM, due out next year, could give medical diagnoses for serial rapists and sex abusers - under labels like "paraphilic coercive disorder" - and may allow offenders to escape prison by providing what could be seen as an excuse for their behavior, they added.

RADICAL, RECKLESS, AND INHUMANE

Simon Wessely of the Institute of Psychiatry at King's College London said a look back at history should make health experts ask themselves: "Do we need all these labels?"

He said the 1840 Census of the United States included just one category for mental disorder, but by 1917 the APA was already recognizing 59. That rose to 128 in 1959, to 227 in 1980, and again to around 350 disorders in the fastest revisions of DSM in 1994 and 2000.

Allen Frances of Duke University and chair of the committee that oversaw the previous DSM revision, said DSM-5 would "radically and recklessly expand the boundaries of psychiatry" and result in the "lexicalization of normality, individual difference, and criminality."

David Pilgrim of Britain's University of Central Lancashire said it was "hard to avoid the conclusion that DSM-5 will help the interests of the drug companies."

"Madness and misery exist but they come in many shapes and sizes," he said. "We risk treating the experience and conduct of people as if they are botanical specimens waiting to be identified and categorized in rigid boxes.

"That would itself be a form of collective madness for all those complicit in the continuing pseudo-scientific exercise."

Nick Craddock of Cardiff University's department of psychological medicine and neurology, who also spoke at the London briefing, cited depression as a key example of where DSM's broad categories were going wrong.

Whereas in previous editions, a person who had recently lost a loved one and was suffering low moods would be seen as experiencing a normal human reaction to bereavement, the new DSM criteria would ignore the death, look only at the symptoms, and class the person as having a depressive illness.

Other examples of diagnoses cited by experts as problematic included "gambling disorder," "internet addiction disorder" and "oppositional defiant disorder" - a condition in which a child "actively refuses to comply with majority's requests" and "performs deliberate actions to annoy others."

"That basically means children who say 'no' to their parents more than a certain number of times," Kinderman said. "On that criteria, many of us would have to say our children are mentally ill."

(Editing by Andrew Heavens)

Source

The trials of creating a hepatitis C vaccine

Oxford Clinical Trials

New research from the University of Oxford is using cutting-edge science to solve the problems associated with creating a hepatitis C vaccine

Hepatitis C is a problematic disease, for patient and clinician alike. In the UK, up to 500,000 people may be infected with the virus, and globally the World Health Organization believes the figure could be as high as 170 million people. Particularly troubling is the fact that the virus can go unnoticed for years, but during that time is capable of causing considerable liver damage.

But weight of numbers isn’t the only difficulty. In fact, perhaps the biggest barrier to creating an effective hepatitis C vaccine is the fact that the virus changes its appearance, making it hard to find a point to target in order to defeat it. “One of the big issues is the variability of the virus,” explains Dr Ellie Barnes form the Jenner Institute. “In fact, it’s ten times more variable than HIV.”

A team at the Jenner Institute led by Dr Barnes have, however, been working to create a vaccine that manages to target the small part of the virus that never changes. To do that, they captured roughly two thirds of the hepatitis C genome, and then attached it to rare adenoviruses -- essentially, strains of the common cold. By using rare adenoviruses, one of which was derived from chimpanzees, itself a world-first, the team could be sure that patients had never been exposed to them before -- a fundamental requirement for the vaccine to work.

As the team report in Science Translational Medicine, they have so far conducted a phase 1 trial in 41 patients, and the results are promising. In fact, the vaccine has been shown to produce a very strong immune response, which lasted a year, and had no major side-effects.

Prof Paul Klenerman, also of the Jenner Institute said: "The immune responses we've seen are exciting and we are beginning the next stage of trials. While we are hopeful, it could be a long road to any vaccine that protects people against hepatitis C."

The next step is to move the research forward into phase 2 trials, testing whether the vaccine can protect people who are at risk of contracting hepatitis C. In fact, those trials are already under development in the US, funded by the NIHR, and are due to commence in late 2012.

Read more in Science Translational Medicine

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New website: NIH Clinical Research Trials and You

For Immediate Release
Monday, February 6, 2012

Contact:
NIH Office of Communications
301-496-5787

Agency-wide resource provides important information for the public and health care providers

The National Institutes of Health has created a new website, NIH Clinical Research Trials and You to help people learn more about clinical trials, why they matter, and how to participate. From the first cure of a solid tumor with chemotherapy to the use of nitroglycerin in response to heart attacks, clinical research trials — or research studies involving people — have played a vital role in improving health and quality of life for people around the globe.

Clinical trials are essential for identifying and understanding ways to prevent, diagnose, and treat disease. Research has shown that among the greatest challenges to recruitment of volunteers is the lack of general knowledge about what trials involve, where they are carried out, and who may participate.

"The ability to recruit the necessary number of volunteers is vital to carrying out clinical research that leads to health and medical advances," said NIH Director Francis S. Collins, M.D., Ph.D. "This new, centralized resource will make it much easier for the public and health professionals to learn about clinical trials and how people can participate in them."

Visitors to the website will find information about:

• The basics of clinical trial participation
• First hand experiences from actual clinical trial volunteers
• Explanations from researchers
• Links on how to search for a trial or enroll in a research matching program

In addition, health care professionals can read about evidence-based strategies for talking with patients about trials, print audience-tested posters to help promote trials in clinics and offices, and find other educational materials.

NIH supports clinical research trials across the country and throughout the world. NIH’s ongoing effort to raise awareness about clinical research and educate potential clinical trial participants about the option of a clinical trial is vital to developing public support and understanding for how clinical research drives medical discovery and improves health outcomes.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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Low-protein diets for hepatic encephalopathy debunked: let them eat steak

Nutr Clin Pract. 2011 Apr;26(2):155-9.

Cabral CM, Burns DL.

Gastroenterology, Lahey Clinic Medical Center, 41 Mall Road, Burlington, MA 01805, USA. Chad.M.Cabral@Lahey.org

Abstract

Hepatic encephalopathy (HE) is an incompletely understood phenomenon and serves as a poor prognosis in patients with cirrhosis. Confusion from HE can affect the ability to eat adequately. Despite the prevalence of malnutrition in cirrhotic patients in the 1950s, it was reported that bouts of overt HE were controlled with low protein intake. This largely uncontrolled observation led to restriction of protein intake in cirrhotic patients with or without HE and was an accepted standard of care for many decades to follow. Published in 2004, the pivotal article "Normal Protein Diet for Episodic Hepatic Encephalopathy: Results of a Randomized Study" by Cordoba and colleagues was the first controlled study randomizing cirrhotic patients with HE to receive different amounts of dietary protein. At the completion of the study, the authors concluded that a normal-protein diet was safe and did not exacerbate HE. The Cordoba study suggests that low-protein diets should be abandoned. In light of this evidence, nutrition guidelines have proposed that protein restriction should be avoided in patients with HE as protein requirements are increased in cirrhosis. Despite the advice of experts in the field, it has been shown in recent years that some physicians still believe that protein restriction is needed in patients with HE. This belief has not been substantiated in controlled studies, and societal recommendations have changed. There is no real evidence documenting the advantages of protein restriction in HE. On the contrary, Cordoba and colleagues' article has shown that there are disadvantages to restricting protein in HE.

Source

Merck says hepatitis pill hampers HIV Drugs

By Ransdell Pierson

Thu Feb 9, 2012 2:37pm EST

(Reuters) - Merck & Co's recently approved Victrelis treatment for hepatitis C considerably lessens the effectiveness of some widely used medicines against the virus that causes AIDS, Merck and U.S. regulators said in separate reports.

"These drug interactions may be clinically significant for patients infected with both chronic hepatitis C virus and HIV by potentially reducing the effectiveness of these medicines when co-administered," Merck said in a February 6 letter to healthcare professionals.

Victrelis, approved last May, attacks the hepatitis C virus that over decades can lead to cirrhosis and liver failure. A significant percentage of hepatitis patients are also infected with the human immunodeficiency virus, or HIV, which weakens the immune system and is fatal without treatment.

The drug interactions were seen in a study among healthy volunteers who took Victrelis and the widely used HIV treatment Norvir in combination with one of three other anti-HIV pills: Reyataz (atazanavir), Prezista (darunavir) and Kaletra (lopinavir/ritonavir). All of the HIV drugs work by blocking protease, an enzyme the virus requires to replicate.

Victrelis reduced concentrations in the blood of Reyataz, Prezista and Kaletra by an average 49 percent, 59 percent and 43 percent, respectively.

Further, levels of Victrelis itself were reduced by 45 percent among volunteers who took it with Kaletra, and 32 percent among those who took it with a combination of Norvir and Prezista.

ISI Group analyst Mark Schoenebaum said 10 percent to 15 percent of patients with hepatitis C are co-infected with HIV, and the findings could crimp Victrelis sales by as much as 25 percent. But he said the setback would have little impact on Merck's earnings this year or in 2013.

The reduced prospects for Victrelis come even as its sales are being dwarfed by Vertex Pharmaceuticals Inc's Incivek, a rival protease inhibitor that was also approved last May.

The U.S. Food and Drug Administration, in an announcement of the findings that appeared on the agency's website on Wednesday, said patients should not stop taking any of their medicines without talking to healthcare professionals.

Drug interactions had previously been found between Victrelis and another HIV treatment called Sustiva (efavirenz). Sustiva belongs to a family of HIV drugs called non-nucleoside reverse transcriptase inhibitors (NNRTIs).

Merck said it was conducting drug-interaction studies of Victrelis with other HIV drugs. They include Intelence (etravirine), which is also a NNRTI, and Isentress (raltegravir), which belongs to a class of drugs called HIV integrase inhibitors,

Merck shares slid 14 cents to $38.28 in afternoon trading on the New York Stock Exchange.

(Reporting By Ransdell Pierson; editing by John Wallace and Maureen Bavdek)

Source

Also See: Victrelis (boceprevir) and Ritonavir-Boosted Human Immunodeficiency Virus (HIV) Protease Inhibitor Drugs: Drug Safety Communication - Drug Interactions

When Will We Have Interferon-Free Treatment for Hepatitis C?

From Medscape Gastroenterology > Ask the Experts

William F. Balistreri, MD

Authors and Disclosures

Posted: 02/09/2012

Question:

Is it true that we are close to treatment of patients with chronic hepatitis C virus (HCV) infection with an interferon-free regimen?

Response from William F. Balistreri, MD
Professor of Medicine, University of Cincinnati College of Medicine; Staff Physician, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio

A New Era of Therapy

Combination therapy with pegylated interferon (PEG-IFN) and ribavirin long stood as the standard of care for chronic hepatitis C virus (HCV) infection. Although effective in achieving high rates of sustained virologic response (SVR), this combination regimen was associated with troublesome side effects.^[1] Therefore, the development of 2 effective protease inhibitors -- telaprevir and boceprevir -- was hailed as a new era of therapy for patients with HCV genotype 1 infection.^[2] These direct-acting antiviral agents act at specific steps in the viral lifecycle and allow more effective treatment with a shorter duration.

Telaprevir and boceprevir, linear inhibitors of the HCV nonstructural protein 3/4A (NS3/4A) serine protease, were approved by the US Food and Drug Administration for HCV treatment in May 2011. However, the recent American Association for the Study of Liver Diseases (AASLD) recommendations indicate that these direct-acting antiviral agents must be used in combination with PEG-IFN and ribavirin.^[1] This is far from the ideal regimen; because of poor tolerability, many treatment candidates will decide not to pursue treatment or to defer treatment until an IFN-free regimen is available.

An Ideal Strategy for HCV

It is true that an IFN-free regimen is "no longer a dream."^[3] It is now viewed as part of a larger goal: the development and validation of an ideal strategy to treat HCV infection. The long sought-after therapeutic objective is to define a strategy that would be highly effective against allHCV genotypes, simple (oral drugs only, low pill burden, and short duration), and safe and tolerable, with low rates of resistance emergence. The recommended strategy would also assess each potential treatment candidate for interleukin 28B genotype, which is a robust pretreatment predictor of SVR to therapy in patients with genotype 1 chronic HCV infection.^[1]

How close are we? Various compounds, encompassing at least 5 distinct drug classes, are currently under development for the treatment of chronic HCV infection, and the results of trials of several investigational agents were recently published.^[3-5] Many other drug trials were presented at The Liver Meeting 2011: The AASLD 62nd Annual Meeting. These drugs bring us one step closer to the long sought-after ideal: the ability to delete noisome IFN injections from treatment strategies.

Promising Preliminary Results

Let me illustrate by focusing on phase 2 studies presented by 2 groups who reported exciting preliminary results of an investigational agent (PSI-7977) even in the absence of IFN coadministration.^[6,7] PSI-7977, a uridine nucleotide analog polymerase inhibitor, is administered orally once daily and has strong antiviral activity against HCV genotype 1 when used in combination with PEG-IFN and ribavirin. A double-blind placebo-controlled dose-ranging study of PSI-7977 in patients with HCV genotype 1 documented a rapid virologic response (RVR) in 98% of patients, with an end-of-treatment response at 24 weeks in 91%.^[6] The RVR in the placebo group was 19%, and the end-of-treatment response was 50%. Of specific note, all patients with the difficult-to-treat interleukin 28B single-nucleotide polymorphism T/T mutation had an RVR -- all became HCV-negative by week 3, and 100% went on to achieve an SVR.

In another phase 2 study, this investigational compound allowed all patients to achieve an RVR. More than 80% of the treatment group had nondetectable HCV RNA at 2 weeks, and all patients had undetectable levels at 3 weeks.^[7] All patients achieved normalization of serum alanine aminotransferase levels. No serious adverse events were attributable to PSI-7977, and as expected, safety and tolerability were greatest in the IFN-free treatment group.

Thus, PSI-7977 exhibits high-potency antiviral activity against a broad range of HCV genotypes, has a high barrier to resistance, and has a reassuring safety profile. This drug also allowed a shorter duration of therapy for viral clearance. These studies support the continued exploration of this drug and related compounds -- alone, with other direct-acting antiviral agents, or with shorter duration of IFN therapy in patients with all HCV genotypes. Further studies will hopefully confirm the initial excitement and optimism and, of note, will document the spectrum of potential adverse effects.

Getting to IFN-Free Regimens

Within the next 5 years, IFN-free regimens may be a reality and available in the clinic. As Sharma and Lok^[3] stated, "[I]t is possible that some of these regimens will also be ribavirin free. This will be good news for patients who wish to be treated but have to defer treatment because of contraindications to use of PEG-IFN or ribavirin, or out of concerns about their ability to tolerate these medications." The ideal strategy is on the horizon.

References

1. Ghany MG, Nelson DR, Strader DB, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011;54:1433-1444. Abstract
2. Jensen DM. A new era of hepatitis C therapy begins. N Engl J Med. 2011;364:1272-1274. Abstract
3. Sharma P, Lok AS. Interferon-free treatment regimens for hepatitis C: are we there yet? Gastroenterology. 2011;141:1963-1967.
4. Gane EJ, Roberts SK, Stedman CA, et al. Oral combination therapy with a nucleoside polymerase inhibitor (RG7128) and danoprevir for chronic hepatitis C genotype 1 infection (INFORM-1): a randomised, double-blind, placebo-controlled, dose-escalation trial. Lancet. 2010;376:1467-1475. Abstract
5. Zuezem S, Asselah T, Angus P, et al. Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection. Gastroenterology. 2011;141:2047-2055. Abstract
6. Lawitz E, Lalezar JP, Hassanein T, et al. Once-daily PSI-7977 plus PEG/RBV in treatment-naive patients with HCV GT1: robust end of treatment response rates are sustained post-treatment. Program and abstracts of The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting; November 9-13, 2011; Boston, Massachusetts. Abstract 225.
7. Gane EJ, Stedman CA, Hyland RH, et al. Once daily PSI-7977 plus RBV: pegylated interferon-alfa not required for complete rapid viral response in treatment-naive patients with HCV GT2 or GT3. Program and abstracts of The Liver Meeting 2011: American Association for the Study of Liver Diseases (AASLD) 62nd Annual Meeting; November 9-13, 2011; Boston, Massachusetts. Abstract 34.

Source

Tocotrienols Reach Organs, Impart Clinical Benefits

EDISON, NJ— A recently published human study reported orally supplemented tocotrienols (as Tocomin SupraBio®, from Carotech) are distributed to various tissues and vital organs and produce significant clinical benefits. Half of end-stage liver disease patients given the supplement for 12 weeks had a reduced Model for End Stage Liver Disease (MELD) score, while only 20 percent of patients taking tocopherols (the regular vitamin E) had similar score reductions.

The trial was conducted by Chandan K. Sen, Ph.D., and his team from the Ohio State University Medical Center and registered at NIH's ClinicalTirals.gov website. The study was designed to determine the levels of vitamin E isomers in human tissues and vital organs following oral supplementation with Tocomin SupraBio, a patented and bioenhanced natural full spectrum palm tocotrienol softgel.

Among the 80 total study subjects, one group of healthy participants had blood and skin tests and were then given 400 mg/d Tocomin for 12 weeks, while another group of surgical patients provided tissue samples of cardiac muscle, liver, abdominal adipose tissues, and brain tissues, and were randomized to either 400 mg/d tocotrienols (Tocomin) or tocopherols for a mean supplement duration of 20 weeks (range: one to 96 weeks).

The researchers found the healthy subjects had negligible levels of tocotrienols in both blood and skin prior to tocotrienols supplementation; after 12 weeks of supplementation, blood and skin levels of tocotrienols increased. In addition, the observed alpha-tocotrienol concentration in blood was 20-fold higher than the amount required to provide neuroprotection. Further, the adipose tissue in tocotrienol supplemented patients contained approximately 10-times the tocotrienol levels, compared to controls. Tocotrienol supplementation also significantly increased alpha, gamma, and delta-tocotrienol levels in the human brain. According to the researchers, alpha-tocotrienol was transported to human brain at a concentration reported to be neuroprotective in earlier studies. In both heart muscle and liver, alpha, gamma, and delta-tocotrienol levels were significantly higher in tocotrienol supplemented patients as compared to subjects receiving tocopherol alone.

As far as health benefits, the researchers utilized the MELD scoring system, which is clinically used to assess the severity of chronic liver disease—the higher the MELD score, the more severe the condition and increased urgency for liver transplantation. They noted MELD score is a reliable marker for mortality in end-stage liver disease. Over the period of the study the researchers noticed that tocotrienols supplemented end stage liver disease patients experienced a reduction in their MELD scores. Among subjects supplemented with tocopherol alone, only 20 percent (one out of five) experienced reduced MELD score, while 50 percent (seven out of 14) of the tocotrienol supplemented subjects showed MELD score improvement.

In fact, MELD score reduction associated with tocotrienol supplementation was most evident in patients with viral hepatic cirrhosis: four out of six patients (67 percent) with hepatitis C and one single hepatitis B patient had reduced MELD score. Researchers noted standard of care therapy is available for viral hepatitis, but it is poorly tolerated due to its toxicity and side effects.

“It is very exciting to learn from this human study that oral supplementation of bioenhanced palm tocotrienol complex that Tocomin SupraBio, improves accumulation of tocotrienols in the blood, skin, adipose, brain, heart and liver," said WH Leong, VP of Carotech. "The study also shows that Tocomin SupraBio® significantly lowered the MELD score in end stage liver disease patients. and may therefore be an exciting oral supplement with potential to benefit these patients. Tocopherol again did not show the same level of efficacy." He further stated this human study also proved tocotrienols are absorbed and accumulated in vital human organs even in the presence of tocopherol, thereby unequivocally dispelling claims that tocopherol prevents the absorption of tocotrienols.

Editor's Note: For more information on tocotrienols, check out INSIDER's On-Demand webinar entitled, "Partner Series—Natural Vitamin E Tocotrienol in Neuroprotection and Stroke Prevention," as well as the INSIDER Tocotrienols Solution Center , which includes slideshows and video from the recent SupplySide workshop on tocotrienols.

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Victrelis (boceprevir) and Ritonavir-Boosted Human Immunodeficiency Virus (HIV) Protease Inhibitor Drugs: Drug Safety Communication - Drug Interactions

[Posted 02/09/2012]

AUDIENCE: Infectious Disease, Pharmacy

ISSUE: FDA notified healthcare professionals and patients that drug interactions between the hepatitis C virus (HCV) protease inhibitor Victrelis (boceprevir) and certain ritonavir-boosted human immunodeficiency virus (HIV) protease inhibitors (atazanavir, lopinavir, darunavir) can potentially reduce the effectiveness of these medicines when they are used together.

A drug interaction study showed that taking boceprevir (Victrelis) with ritonavir (Norvir) in combination with atazanavir (Reyataz) or darunavir (Prezista), or with Kaletra (lopinavir/ritonavir) reduced the blood levels of the HIV medicines and boceprevir in the body (see Data Summary below). FDA will be updating the Victrelis drug label to include information about these drug interactions.

BACKGROUND: Victrelis is a hepatitis C virus (HCV) protease inhibitor used with the medicines peginterferon alfa and ribavirin to treat chronic (long-lasting) hepatitis C infection in adults. HIV protease inhibitors are a class of anti-viral drugs used to treat HIV infection. Ritonavir is an HIV protease inhibitor used to “boost” other HIV protease inhibitors, increasing their levels in the blood and making them more effective.

RECOMMENDATION: Patients should not stop taking any of their medicines without talking to their healthcare professional. Patients should contact their healthcare professional if they have any questions or concerns.

Healthcare professionals who have started patients infected with both chronic HCV and HIV on Victrelis and antiretroviral therapy containing a ritonavir-boosted protease inhibitor should closely monitor patients for HCV treatment response and for potential HCV and HIV virologic rebound.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[02/09/2012 - Drug Safety Communication - FDA]

[02/06/2012 - Dear Healthcare Professional Letter - Merck]

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Chronic Liver Disease Foundation Issues Statement in Support of Birth-Cohort Screening for Hepatitis C

PRESS RELEASE

Feb. 9, 2012, 12:00 p.m. EST

Recommendations Include Expanded Testing with Rapid Point-of-Care HCV Test

CLARK, N.J., Feb 9, 2012 (GlobeNewswire via COMTEX) -- The Chronic Liver Disease Foundation (CLDF), a leading educational organization dedicated to increasing awareness of the effect of chronic liver disease (CLD) in the United States, issued today a position paper in support of expanding screening for hepatitis C (HCV) in the United States.

The position paper, "Endorsement of Birth-Cohort Approach to Expand Screening for Hepatitis C," outlines the CLDF's recommendations for a more effective strategy to identify patients with HCV infection and link such patients to expert care and treatment.

HCV is the most common blood-borne chronic viral infection in the U.S., with more than four million Americans currently infected with the HCV virus. Of these, up to 75 percent are unaware of their infection. Individuals born between the years of 1945 and 1965 have an HCV prevalence level four times higher than those born outside the birth cohort.

While the CDC currently recommends HCV screening only for individuals found to be at risk for the HCV infection, it is currently evaluating the potential benefits of using a birth-cohort based approach to HCV screening to help increase identification of HCV-positive patients.

The CLDF issued the following recommendations in support of the expansion of HCV screening efforts:

• Routine screening for HCV among persons born between 1945 and 1965
• Use of the OraQuick HCV rapid point-of-care test to expand testing opportunities and facilitate immediate care
• Educational programs aimed at primary care providers to increase awareness of HCV risk factors
• Testing for HCV in primary care setting with established linkages to HCV
• Creative ways to increase access to HCV testing and care for injection-drug users and other underserved populations.

"Today, more than 4 million Americans are infected with hepatitis C and the vast majority does not know it," said Dr. Willis C. Maddrey, President of the Chronic Liver Disease Foundation. "Hepatitis C is a leading cause of chronic liver disease, cirrhosis and liver cancer. However, new therapies are now available that can effectively treat a high percentage of people with HCV infection, making expanded and accessible testing for HCV -- particularly among those born between 1945 and 1965 -- a critical step in fighting this epidemic." 

About the Chronic Liver Disease Foundation

Established in 2001, the Chronic Liver Disease Foundation is a nonprofit 501(c)(3) educational organization dedicated to providing hepatology related continuing medical education, news and information to healthcare professionals across the US. The CLDF is led by a Board of Trustees comprised of nationally renowned liver disease specialists. Furthermore, the CLDF believes that educational programs should be developed by the specialists who are actively involved in the research, treatment and management of a disease. As such, the CLDF has developed a network of 75 Centers of Educational Expertise and multiple Advisory Boards who are actively involved in program creation related to specific disease topics which include: hemochromatosis, hepatic encephalopathy, hepatitis B, hepatitis C, hepatocellular carcinoma, HIV co-infection, liver transplantation and NASH/NAFLD. The CLDF's educational opportunities are offered in a variety of formats including an interactive web site, live meetings, teleconferences, print pieces, webcasts and other electronic mediums. For more information, please visit www.chronicliverdisease.org .

This news release was distributed by GlobeNewswire, www.globenewswire.com 

SOURCE: Chronic Liver Disease Foundation

        CONTACT: CLDF Media Contact:
        mediarelations@chronicliverdisease.org 
        888-565-5321
        
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