Simeprevir data from COSMOS study in Hepatitis C patients will be presented as late-breaking presentation at AASLD

Stockholm, Sweden — Medivir AB (OMX: MVIR) announced that data from the phase IIa COSMOS study (Combination Of SiMeprevir and sOfosbuvir in HCV genotype 1 infected patientS) of the investigational protease inhibitor simeprevir (TMC435) administered once daily with Gilead’s investigational nucleotide inhibitor sofosbuvir (GS-7977), with and without ribavirin, in genotype 1 chronic hepatitis C adult patients with compensated liver disease has been accepted as a late-breaking oral presentation at the upcoming Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). AASLD will take place November 1 to 5 in Washington, D.C.

The COSMOS data will be presented during the late-breaking oral session on Monday, November 4, 2:45-4:30 p.m. (EST) in Hall E:
SVR results of a once-daily regimen of simeprevir (TMC435) plus sofosbuvir (GS-7977) with or without ribavirin in cirrhotic and non-cirrhotic HCV genotype 1 treatment-naïve and prior null responder patients: The COSMOS study.

• Lead Author: Ira M. Jacobson, Weill Cornell Medical College, New York, USA

Full session details and data presentation listings for the 2013 AASLD Annual Meeting can be found at http://www.aasld.org/livermeeting.

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR
Mobile: +46 708 537 292.

About Simeprevir
Simeprevir is an investigational NS3/4A protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, for the treatment of genotype 1 and genotype 4 chronic hepatitis C in adult patients with compensated liver disease, including all stages of liver fibrosis. Simeprevir works by blocking the protease enzyme that enables the hepatitis C virus to replicate in host cells.

Janssen is responsible for the global clinical development of simeprevir and has acquired exclusive, worldwide marketing rights, except for in the Nordic countries. Medivir will retain marketing rights for simeprevir in these countries.

Simeprevir was approved in Japan in September 2013 for the treatment of genotype 1 hepatitis C. In the U.S., the New Drug Application (NDA) filed by Janssen for simeprevir administered once daily in combination with pegylated interferon and ribavirin for the treatment of genotype 1 chronic hepatitis C in adult patients was granted Priority Review designation by the Food and Drug Administration (FDA) in May. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April seeking approval of simeprevir for the treatment of genotype 1 or genotype 4 chronic hepatitis C.

To date, more than 3,700 patients have been treated with simeprevir in clinical trials. Simeprevir is also being studied in several interferon-free regimens using selected combinations of direct-acting antiviral agents with different mechanisms of action.

For additional information about simeprevir clinical trials, please visit www.clinicaltrials.gov.

About Sofosbuvir
Sofosbuvir (formerly referred to as GS-7977) is a once-daily nucleotide analog polymerase inhibitor for the treatment of HCV infection being developed by Gilead Sciences, Inc. Sofosbuvir is being evaluated as part of multiple therapeutic regimens, including programs with RBV alone and in combination with peg-IFN and RBV.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases.
Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

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Oversight Reduces HIV Prescription Errors

Laird Harrison

Oct 05, 2013

SAN FRANCISCO — Better record keeping, education, and vigilance by infectious disease clinicians and pharmacists can reduce the rate of prescription errors for HIV-infected patients hospitalized for other reasons, new research shows.

Such reforms significantly reduced the rate of prescribing errors from 50% to 34% at the Cleveland Clinic(P = .008), said Elizabeth Neuner, PharmD, an infectious diseases clinical pharmacist. "They allow more effective prescribing."

Dr. Neuner presented the research to reporters attending a news conference here at IDWeek 2013.

Antiretroviral drug regimens for HIV are typically complicated and can be difficult for patients to follow, she noted.

When HIV-infected patients are hospitalized for non-HIV conditions, hospital providers who are unfamiliar with the complexities of HIV therapy can make errors. The consequences include adverse effects, a loss of viral protection, and drug interactions, she told Medscape Medical News.

"We wanted to take a more focused look at those patients because they are at such high risk for medication errors," she said.

To reduce these errors, the Cleveland Clinic implemented a program that involved education, modification of the electronic drug file to help guide the accurate prescribing of medications, a daily medication profile review by a pharmacist specializing in HIV, and the involvement of an infectious disease physician.

In their study, Dr. Neuner and her team evaluated 162 HIV-infected patients hospitalized for another reason before the program was implemented and 110 patients hospitalized after it started.

Table. Prescribing Errors Before and After Program Implementation

Outcome	Preprogram	Postprogram	P Value
Errors resolved	36%	74%	.001
Time to resolve errors	180 hours	23 hours	.002
Cases with errors	50%	34%	.008

The researchers found that infectious disease specialists provided valuable input. Errors were corrected more often when patients were evaluated by a specialist than when they were not (68% vs 32%; P = .002).

For example, the specialists corrected inaccurate antiretroviral medications and dosages, adjusted regimens in which a new medication, such as for heart problems or diabetes, was interacting with an antiretroviral medication, and revised therapy to address a new problem, such as kidney injury.

In some cases, physicians opted not to correct the error because the patient was doing well on the therapy and the benefits outweighed the risks.

Michael Horberg, MD, national director for HIV/AIDS at Kaiser Permanente Medical Group in Rockville, Maryland, pointed out that Kaiser hospitals are using a similar system to prevent errors.

"When these patients come in, they sometimes remember to bring their medications, and they sometimes don't," he told Medscape Medical News. "If we can't get hold of their primary care physician, we're at a loss. In such cases, the roles of the infectious disease clinician and pharmacist are increasingly critical to quality of care and quality outcomes."

Dr. Horberg and Dr. Neuner have disclosed no relevant financial relationships.

IDWeek 2013. Abstract 176. Presented October 3, 2013.

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Early Metabolic and Hepatic Lipid Gene Expression Changes in Chronic Hepatitis C Patients Treated with an Interferon-free Regimen

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

1830. Early Metabolic and Hepatic Lipid Gene Expression Changes in Chronic Hepatitis C Patients Treated with an Interferon-free Regimen

Session: Oral Abstract Session: Hepatitis C

Saturday, October 5, 2013: 3:15 PM

Room: The Moscone Center: 250-262

Background: Hepatitis C (HCV) modulates the intrahepatic VLDL synthetic pathway as part of its natural life cycle. Chronic HCV (CHC) infection is associated with an altered metabolic state including dyslipidemia and insulin resistance, contributing to disease progression and reduced response to therapy. The interactions between HCV replication and host lipid pathways are incompletely understood.

Methods: Sixty CHC genotype-1, treatment-naive patients were treated with 24 weeks of the HCV NS5B inhibitor sofosbuvir in combination with low or full dose ribavirin. Serum lipids and hemoglobin A1C (HbA1c) were measured at various time points. Targeted quantitative RT-PCR for lipid and glucose metabolism related genes was performed on paired liver biopsy specimens obtained from 7 patients before and at end-of treatment (EOT). 

Results: Of 55 patients who completed the study, 38 patients achieved a sustained virologic response (SVR₂₄) and 17 patients relapsed after EOT.  Between baseline and week 4 of therapy, LDL significantly increased (91 ± 4 to 104 ± 5 mg/dl, p=.0027) and triglycerides decreased (137 ± 10 to 98 ± 8 mg/dl, p<.0001) which persisted through EOT. Compared to patients who achieved SVR₂₄, LDL was significantly lower in patients who eventually relapsed both at baseline (97 ± 5 vs 78 ± 7 mg/dl; p=0.031) and at week 48 (109 ± 6 vs 82 ± 7mg/dl; p=0.005), while there was no difference during or at EOT (Fig 1A). Triglycerides differed by treatment outcome only after EOT (Fig 1B). No changes in HDL were observed. HbA1C decreased significantly (5.58 to 5.45) in the 39 patients with paired values obtained at baseline and 24 weeks after EOT (p=0.0033) and this was independent of treatment outcome (Figure 1C). Intrahepatic gene expression of lipid transport genes (APOB, APOC3, APOL3) was significantly up-regulated, while lipid assembly and signaling genes (LEPR, MTTP) were down-regulated at EOT in 7 patients with paired liver biopsies (all achieved SVR₂₄).    

Conclusion: Our data demonstrate changes in lipid metabolism pathways and glucose homeostasis in CHC genotype-1 infection following interferon-free antiviral therapy.  The early changes in LDL and triglycerides associated with treatment implicate a direct effect of viral clearance on lipid homeostasis.    

Eric Meissner, MD, PhD¹, Anu Osinusi, MD, MPH^1,2, Jing Qin, PhD³, Yu-Jin Lee, BA³, Susanna Naggie, MD⁴, Keyur Patel, MD⁴, John Mchutchison, MD⁵, Henry Masur, MD, FIDSA⁶ and Shyam Kottilil, MD, PhD¹, (1)NIAID/NIH, Bethesda, MD, (2)Clinical Research Directorate/Cmrp, Saic-Frederick, Inc., Frederick, MD, (3)Niaid/NIH, Bethesda, MD, (4)Duke University Medical Center, Durham, NC, (5)Gilead Sciences, Foster City, CA, (6)National Institutes of Health - Dept of Critical Care, Bethesda, MD

Disclosures:

E. Meissner, None

A. Osinusi, None

J. Qin, None

Y. J. Lee, None

S. Naggie, Gilead Sciences: Grant Investigator and Scientific Advisor, Consulting fee and Grant recipient

K. Patel, Gilead Sciences: Consultant and Scientific Advisor, Consulting fee

J. Mchutchison, Gilead Sciences: Employee and Shareholder, Salary

H. Masur, None

S. Kottilil, None

Source

Hepatitis C education crucial to cut high infection rate in Middle East and North Africa

Jennifer Bell

October 6, 2013 Updated: October 6, 2013 21:13:00

DUBAI // The Middle East and North Africa region has one of the highest rates of hepatitis C in the world, experts have revealed.

About nine million people in the region are believed to be infected with the potentially lethal virus, which can lead to cirrhosis of the liver or liver cancer.

In the UAE alone, about 14 in every 100,000 people will become infected at some point in their lives.

The figures were revealed during a conference in Dubai that brought together more than 200 doctors to discuss the virus, the best ways to manage it and the medical breakthroughs that may help to reduce its growing prevalence.

According to the World Health Organisation, about 150 million people globally are chronically infected with hepatitis C, and more than 350,000 people die from related liver diseases each year.

“Despite the progress and medical breakthroughs that have taken place over the last decade, hepatitis C transmission rates in the Mena region are still among the highest in the world,” said Ramsey Morad from the healthcare company MSD, which organised the conference.

“Education is crucial if we are truly to start addressing this epidemic.”

In the UAE, the virus is most prevalent in Abu Dhabi, according to MSD, and least common in Ajman.

Mazen Altaruti, the managing director of MSD Gulf, described the virus, which is mainly transmitted through blood-to-blood contact, as a “silent killer” as most patients show no symptoms until it has caused irreversible liver damage.

jbell@thenational.ae

Source

Also See: Media academy held to support prevention and treatment of hepatitis C in Middle East

Rates and Causes of Mortality among People in Care with Hepatitis C Virus Infection — Chronic Hepatitis Cohort Study (CHeCS), 2006–2010

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

1774. Rates and Causes of Mortality among People in Care with Hepatitis C Virus Infection — Chronic Hepatitis Cohort Study (CHeCS), 2006–2010

Session: Poster Abstract Session: Viral Infections; Pathogenesis and Epidemiology

Saturday, October 5, 2013

Room: The Moscone Center: Poster Hall C

Posters Mahajan- IDSA- 9-2013.pdf (397.6 kB)

Background: To examine the association of hepatitis C virus (HCV) infection with all-cause and liver-related mortality, we analyzed data from a prospective observational cohort study in four health care systems in the United States.

Methods: We examined electronic health records of adults with at least one health system encounter from January 2006 through December 2010 from four integrated health care systems, and created a cohort of confirmed HCV-infected patients [Chronic Hepatitis Cohort Study (CHeCS)]. Cohort patients who died during 2006-2010 were analyzed.   All-cause and disease-specific death rates were calculated based upon US census data from 2006-2010.  Total number of deaths came from Multiple Cause of Death (MCOD) data based on 12 million death certificates for U.S. residents for the same time period.

Results: Of 2,143,369 adult patients with an encounter with the four CHeCS sites during 2006-2010, 11,703 (0.5%) had diagnosed chronic HCV infection. Of these, 1,590 (14%) died during 2006–2010; 75% of whom were born between 1945-1965, 50% were white, and 68% were men. Primary cause of death (498 of 1590) was liver disease unrelated to alcohol. Despite confirmed chronic HCV infection in those who died, only 19%had HCV infection listed as an underlying cause of death, and only 32% among those who died of primary liver cancer.   Mean age of death for HCV patients (59 years) was 15 years younger than in those without HCV infection from national data.  The age-adjusted mortality rate for liver disease in CHeCS was twelve times higher than the MCOD rate. 

Conclusion:    HCV infection was not listed as a cause of mortality in approximately 80% of confirmed HCV-infected persons; currently only 15,000 deaths have HCV infection listed on the death certificate.  Our data suggests that the national mortality rate of those with HCV could be as high as 75,000 persons per year, with over 60% of current deaths in our HCV-infected cohort directly attributable to liver disease.  Whether ascribed to liver-related causes or not, mortality in HCV-infected persons was 15 years younger compared with the national average in non-HCV infected persons.

Reena Mahajan, MD, MHS¹, Jian Xing, PhD¹, Stephen Liu, MPH¹, Kathleen Ly, MPH¹, Anne C. Moorman, BSN, MPH¹, Lora Rupp, MSE, MBA², Fujie Xu, MD, PhD¹, Scott Holmberg, MD, MPH¹ and for the Chronic Hepatitis Cohort Study (CHeCS) Investigators, (1)Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, (2)Center for Health Services Research, Henry Ford Health System, Detroit, MI 

Disclosures:

R. Mahajan, None

J. Xing, None

S. Liu, None

K. Ly, None

A. C. Moorman, None

L. Rupp, None

F. Xu, None

S. Holmberg, None

Source

Rapid Hepatitis C Virus Testing: An Innovative Pilot Study for Testing and Linking High Risk Populations from a Mobile Healthcare Clinic

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

1756. Rapid Hepatitis C Virus Testing: An Innovative Pilot Study for Testing and Linking High Risk Populations from a Mobile Healthcare Clinic

Session: Poster Abstract Session: Viral Infections; Pathogenesis and Epidemiology

Saturday, October 5, 2013

Room: The Moscone Center: Poster Hall C

Posters IDSA.2013.#41989.Morano.pdf (1.4 MB)

Background: After recent release of effective HCV treatments, CDC guidelines aim to increase HCV testing and linkage to treatment for certain high-risk populations. This approach has not, however, been empirically tested using rapid HCV testing strategies.

Methods: An innovative rapid HCV testing campaign was deployed from a mobile medical clinic (MMC) in New Haven, CT using routine medical intake information. Clients could select rapid versus traditional phlebotomy testing.  Traditional testing included phlebotomy for other medical co-morbidities, including syphilis, hepatitis B, and chronic medical conditions.  Independent correlates of: 1) type of HCV testing strategy; and 2) reactive HCV antibody results were assessed. Linkage to HCV care was defined as completing one follow-up clinical visit in person with confirmatory HCV testing.

Results: All of 190 clients approached from March 2012 to March 2013 accepted HCV testing; 154 (81.1%) chose rapid HCV testing. Overall, 17 (8.9%) were HCV+, with 13 (8.4%) in the rapid and 4 (11.1%) in the traditional group.  Generally, participants were mean age 35.9 years, previously incarcerated (51.1%), had >15 lifetime sexual partners (81.6%), were US-born (84.7%), had used illicit drugs (75.3%), and previously tattooed (64.2%).  Of the 60 (31.6%) people who inject drugs (PWID), only 9 (15.0%) were within the “baby boomer” cohort.

Independent correlates of choosing rapid HCV testing over phlebotomy were non-PWID (AOR 25.0; p=0.027) and less than 15 lifetime sexual partners (marginal effect 0.17; p=0.003). Independent correlates of being HCV+ were being non-Hispanic White (AOR 15.2; p=0.002), reported sex with a known HCV+ partner (AOR 33.0; p<0.001), and increasing age (AOR 1.08; p=0.003). Among the 17 HCV+ patients, only 7 (53.8%) were within the “baby boomer” cohort, and 12 (70.6%) were successfully linked to HCV care.  

Conclusion: The majority of individuals prefer rapid HCV testing, yet higher risk individuals opted for traditional phlebotomy testing, perhaps to identify other comorbid conditions. Rapid testing, however, identified the majority of new HCV infections, using an innovative MMC model which successfully engaged individuals who might otherwise not have been tested in traditional healthcare settings. Risk-based testing thus necessarily augments the “baby boomer” HCV screening age category.

Jamie Morano, MD, MPH¹, Alexei Zelenev, PhD², Andrea Lombard, RN, BSN, MPH, CIC³, Britton Gibson, MPH², Ruthanne Marcus, MPH⁴ and Frederick Altice, MD⁵, (1)Department of Infectious Diseases, Yale University School of Medicine, Yale Clinical Research, Yale University AIDS Program, Center for Interdisciplinary Research on AIDS, New Haven, CT, (2)Yale University School of Medicine, Yale University AIDS Program, New Haven, CT, (3)Viral Hepatitis Section, Connecticut Department of Public Health, Hartford, CT, (4)Yale Clinical Research, Yale University AIDS Program, Yale School of Public Health, New Haven, CT, (5)Yale University School of Medicine, Yale School of Public Health, Director, Yale University AIDS Program, Yale Clinical and Community Research, Yale Center for Interdisciplinary Research on AIDS, New Haven, CT

Disclosures:

J. Morano, Vertex Pharmaceuticals Circle of Care Hepatitis C Grant: Grant Investigator, Research grant and Research support

A. Zelenev, None

A. Lombard, None

B. Gibson, Vertex Pharmaceuticals: Collaborator, Salary

R. Marcus, None

F. Altice, Vertex Pharmaceuticals Circle of Care Hepatitis C Grant: Investigator, Research grant and Supporting Mobile Clinic Work for HCV Testing; No Drug Support Given

Source

Daclatasvir + Sofosbuvir Effective in Prior Telaprevir or Boceprevir Failures

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

1357. Sustained Virologic Response With Daclatasvir Plus Sofosbuvir ± Ribavirin (RBV) In Chronic HCV Genotype (GT) 1-Infected Patients Who Previously Failed Telaprevir (TVR) Or Boceprevir (BOC)

Session: Poster Abstract Session: Clinical Trials

Saturday, October 5, 2013

Room: The Moscone Center: Poster Hall C

Background: Daclatasvir (DCV) plus sofosbuvir (SOF) ±RBV achieved high rates of sustained virologic response in HCV GT1-3-infected previously untreated patients (arms A-H). Additional arms (I, J) evaluated the efficacy of DCV+SOF ±RBV in patients who failed TVR or BOC.

Methods: A total of 41 GT1 non-cirrhotic patients with previous breakthrough (n=15), relapse (n=13), or nonresponse (n=14) to pegIFN/RBV+TVR (n=33) or BOC (n=9) (1 patient received both) were randomized 1:1 to DCV+SOF with or without RBV for 24 weeks. Patients who discontinued TVR or BOC due to adverse events were excluded. DCV and SOF were dosed orally at 60mg QD and 400mg QD, respectively. RBV was dosed BID at 1000-1200 mg/d. The primary end point was HCV RNA<25 IU/mL at 12 weeks post-treatment (SVR₁₂).

Results: Most patients had HCV GT1a (83%), were IL28B non-CC (98%), and had estimated METAVIR stage ≥F2 (83%). Mean HCV RNA was ≥6 log IU/mL. HCV RNA <25 IU/mL was achieved in 40/41 patients by week 4 and in all patients by end of treatment. None had breakthrough or relapse and all patients with available data (40/41) achieved SVR₁₂ (Table). The most common adverse events (>30% total) were fatigue and headache. There were no grade 3-4 hematologic or hepatic laboratory abnormalities. 

Conclusion : The all-oral, once-daily combination of DCV+SOF with or without RBV for 24 weeks achieved SVR₁₂ in 98% of non-cirrhotic GT1 prior TVR/BOC treatment failures. These data provide proof-of-concept that the combination of two potent direct-acting antivirals with different viral targets is effective in patients who failed pegIFN/RBV + a protease inhibitor.

HCV RNA < 25 IU/mL, mITT	I DCV + SOF x 24 weeks (n = 21)	J DCV + SOF  + RBV x 24 weeks (n = 20)
Week 4	21 (100)	19 (95)a
End Of Treatment  (Week 24)	21 (100)	20 (100)
SVR4	21 (100)	20 (100)
SVR12	21 (100)	19 (95)b
a 1 missing; b 1 missing—patient had HCV RNA undetectable at post-treatment  week4 and post-treatment week 24 (preliminary)

Mark Sulkowski, MD¹, David Gardiner², Maribel Rodriguez-Torres, MD³, K. Rajender Reddy, MD⁴, Tarek Hassanein, MD⁵, Ira Jacobson, MD⁶, Eric Lawitz⁷, Anna S.F. Lok, MD, FRCP⁸, Federico Hinestrosa⁹, Paul J. Thuluvath¹⁰, Howard Schwartz¹¹, David Nelson¹², Gregory T. Everson¹³, Timothy Eley, PhD¹⁴, Megan Wind-Rotolo¹⁵, Shu-Pang Huang¹⁵, Min Gao¹⁶, Fiona Mcphee¹⁶, Dennis Hernandez¹⁶, Diane Sherman², Robert Hindes¹⁷, William Symonds, PharmD¹⁸, Claudio Pasquinelli¹⁴, Dennis Grasela, PharmD, PhD¹⁹ and AI444040 Study Group, (1)John Hopkins University School of Medicine, Baltimore, MD, (2)Bristol-Myers Squibb, Pennington, NJ, (3)Gastroenterology, Fundacion de Investigacion, Rio Piedras, PR, (4)Univ. of Pennsylvania, Philadelphia, PA, (5)230 Prospect Place, Suite 220, Southern California Liver Centers, Coronado, CA, (6)Weill Medical College of Cornell University, New York, NY, (7)Texas Liver Insititute, University of Texas Health Science Center, San Antonio, TX, (8)Internal Medicine, University of Michigan, Ann Arbor, MI, (9)Orlando Immunology Center, Orlando, FL, (10)Mercy Medical Center, Baltimore, MD, (11)Miami Research Associates, South Miami, FL, (12)University of Florida, Gainesville, FL, (13)University of Colorado Denver, Aurora, CO, (14)Bristol-Myers Squibb, Hopewell, NJ, (15)Bristol-Myers Squibb, Princeton, NJ, (16)Bristol-Myers Squibb, Wallingford, CT, (17)Consultant, Foster City, CA, (18)Gilead Sciences, Foster City, CA, (19)Bristol Myers-Squibb, Hopewell, NJ

Disclosures:

M. Sulkowski, AbbVie: Investigator and Scientific Advisor, Consulting fee and Research grant
BIPI: Investigator, Research Contractor and Scientific Advisor, Consulting fee and Research grant
BMS: Investigator and Scientific Advisor, Consulting fee and Research grant
Gilead : Investigator and Scientific Advisor, Consulting fee and Research grant
Janssen: Consultant, Investigator and Scientific Advisor, Consulting fee and Research grant
Merck : Investigator and Scientific Advisor, Research grant
Pfizer: Steering Committe, Consulting fee
Vertex: Investigator and Scientific Advisor, Consulting fee and Research grant

D. Gardiner, Bristol-Myers Squibb: Employee, Salary

M. Rodriguez-Torres, Bristol-Myers Squibb: Investigator, Research support

K. R. Reddy, Bristol-Myers Squibb: Investigator, Research support

T. Hassanein, Bristol-Myers Squibb: Investigator, Research support

I. Jacobson, Bristol-Myers Squibb: Investigator, Research support

E. Lawitz, Bristol-Myers Squibb: Investigator, Research support

A. S. F. Lok, Bristol-Myers Squibb: Investigator, Research support

F. Hinestrosa, Bristol-Myers Squibb: Investigator, Research support

P. J. Thuluvath, Bristol-Myers Squibb: Investigator, Research support

H. Schwartz, Bristol-Myers Squibb: Investigator, Research support

D. Nelson, Bristol-Myers Squibb: Investigator, Research support

G. T. Everson, Bristol-Myers Squibb: Investigator, Research support

T. Eley, Bristol-Myers Squibb: Employee, Salary

M. Wind-Rotolo, Bristol-Myers Squibb: Employee, Salary

S. P. Huang, Shu-Pang Huang: Employee, Salary

M. Gao, Bristol-Myers Squibb: Employee, Salary

F. Mcphee, Bristol-Myers Squibb: Employee, Salary

D. Hernandez, Bristol-Myers Squibb: Employee, Salary

D. Sherman, Bristol-Myers Squibb: Employee, Salary

R. Hindes, Bristol-Myers Squibb: Research Contractor, Research support

W. Symonds, Gilead Sciences: Employee, Salary

C. Pasquinelli, Bristol-Myers Squibb: Employee, Salary

D. Grasela, Bristol-Myers Squibb: Employee, Salary

Source

Media academy held to support prevention and treatment of hepatitis C in Middle East

United Arab Emirates: 1 hour, 21 minutes ago

As part of their ongoing commitment to reducing the growing epidemic that hepatitis C (HCV) has become in the Middle East, MSD hosted the HCV Middle East summit, which brought together more than 200 doctors from across the region to discuss the virus, the best ways to manage it and the medical breakthroughs that may help to reduce the virus's growing prevalence.

Over the course of two days, MSD brought together both international and regional medical experts to present on a range of topics, highlighting the latest clinical trials and medical advances that may help save the lives of hepatitis C sufferers.

More than 9 million people across the MENA region are already believed to be infected with hepatitis C, additionally, whilst statistics remain scarce it is estimated that as much as 13.9 people out every 100,000 UAE citizens may suffer from the virus.

On the sidelines of this conference and as part of MSD's ongoing commitment to reducing the prevalence of life threatening illnesses through continuous, MSD also hosted a media academy for more than 25 journalists from countries across the Middle East. Hosted at the Grand Hyatt in Dubai, the Academy which brought together local and regional Gastroenterologists, as well as MSD experts, covered a wide range of topics including the prevalence and causes of hepatitis C, the various treatment options available as well as those in the pipeline and the integral role the media plays in helping to reduce the hepatitis epidemic.

Talking about their decision to host both the medical conference and media academy, Dr. Ramsey Morad, Managing Director of MSD in the Middle East, said, "At MSD we are committed to providing continuous education, whether to support physicians in providing their patients with the best care possible, or whether we are working with the media, to ensure that they have the tools they need to support in raising public awareness. Hepatitis C has already become an epidemic, with WHO estimating that 3% of the world's population, or around 170 million are already infected with the virus. As a region, the Middle East and North Africa, already ranks amongst the highest in the world in terms of both prevalence and incidence. Despite the progress and medical breakthroughs that have taken place over the last decade, hepatitis C transmission rates in the MENA region, are still amongst the highest in the world. Education is crucial if we are truly to start addressing this epidemic."

Adding to Dr. Morad's comments, Mr. Mazen Altaruti, Managing Director of MSD Gulf, said, "Hepatitis C is often known as the silent killer, because in many cases there are no specific symptoms until they have advanced or become chronic hepatitis. By raising awareness and providing physicians and the general public with a better understanding of the virus and the ways to prevent it we can save the lives of the UAE citizens."

The conference and media academy are just the latest in a long line of initiatives that MSD has undertaken in the region over the last few years to try to raise awareness of hepatitis C, just some of these initiatives including free screenings and continuous education programs for physicians and medical professionals, like the Middle East School of Hepatology, that MSD launched earlier this year.

Dr. Ramsey Morad, Managing Director of MSD in the Middle East.

Source

"The first and only preventative HIV vaccine based on a genetically modified killed whole virus (SAV001-H) holds tremendous promise for success in the final phases of clinical testing now that the first hurdle has been accomplished"

Provided by NATAP

Recruiting Safety and Immune Response Assessment Study of Killed-whole HIV-1 Vaccine (SAV001-H) in Chronic HIV-1 Infected Patients

"The antibody against p24 capsid antigen increased as much as 64-fold in some vaccinees while the antibody against gp120 surface antigen increased up to eight-fold. P24 is a structural protein that makes up most of the HIV viral core also known as the 'capsid.' High levels of p24 are present in the blood serum of newly infected individuals during the short period between infection and seroconversion, making p24 antigen assays useful in diagnosing primary HIV infection. A glycoprotein, gp120, is necessary for attachment to cell surface receptors and also allows for the HIV virus to enter cells."

"Preliminary findings for SAV001-H have not only shown promise, but have exceeded expectations. Phase I of the clinical trials was approved and commenced with a small sample of HIV positive volunteers located at two clinics within Los Angeles. A sample size of 40 men and women were assigned to groups, with eighteen receiving the vaccine and six receiving the placebo. None of the participants given the vaccine suffered any adverse effects."

--------------------------------

SAV001-H: HIV Vaccine Has No Adverse Side Effects In Early Trial

http://www.huffingtonpost.com

Pharmaceutical company Sumagen Canada announced yesterday the successful completion of a Phase 1 Clinical Trial of SAV001-H, a vaccine against HIV and AIDS. The trial ran for over a year, from March 2012 through last month, and was designed to test the "safety, tolerability and immune responses" of the drug in real live human subjects. Phase 1 trials are the point at which researchers go from seeing whether their drugs work in animals to making sure that they don't do weird and bad stuff to people, so the stakes are obviously very high.

SAV001-H passed flawlessly: in the randomized, observer-blinded, placebo-controlled study of HIV-infected, asymptomatic men and women, there were "no serious adverse event[s]," meaning that Phase 2 trials (seeing how well the vaccine actually works) can come next.

SAV001-H is what's called a "killed whole virus vaccine," meaning that it includes actual HIV viruses. This sounds like something that you don't want to get injected with, but as part of the vaccine-making process, the live HIV viruses are genetically re-engineered to eliminate pathogenicity, chemically treated, and then irradiated with gamma rays to make sure that they're dead dead dead. While other HIV/AIDS vaccines that haven't used killed whole viruses (relying instead on targeting specific components of HIV) have failed in Phase 3 trials, Sumagen is optimistic about their drug because other successful vaccines (including polio, influenza, rabies, and hepatitis A) work on the same principle.

The vaccine prevents HIV infection by massively boosting the production of a variety of antibodies in the human immune system. We won't get detailed statistics on how effective SAV001-H is until the completion of the Phase 2 trials, but even during Phase 1, the researchers were able measure boosts in the production of a variety HIV-specific antibodies ranging anywhere from eight to 64 times higher than with a placebo. Plus, these increases in antibodies were maintained over the entire duration of the study. Based on these data, Sumagen is "[forecasting] a success of the Phase 2 human clinical trial."

It would be premature to get too excited about this, since many vaccines encounter issues in Phase 2 and Phase 3 clinical trials. But, we're excited anyway. 35 million people have died of HIV/AIDS, and nearly as many are currently infected. 40% of new infections occur in people between the ages of 15 and 24. According to Sumagen, when this vaccine comes to market (and it's getting closer), it could mean "the eradication of HIV/AIDS for human beings." Eradication. Forever.

---------------------------------

http://www.pharmaceutical-technology.com/features/featuretrialing-first-ever-hiv-vaccine-human-clinical

Trialling the first ever HIV vaccine

24 January 2013

In October 2012, Canadian scientists announced that they may have discovered the first and only preventative HIV vaccine that has shown no adverse effects in Phase I human clinical trials. Despite the failure of all previous attempts, the promise of a vaccine with no adverse side effects has ignited a new surge of hope in the fight against HIV, but how does this vaccine differ? Dr Nicola Davies reports.

The HIV virus has posed great challenges for scientists, primarily because of the way the virus compromises the body's immune system. The HIV virus is what is termed as a "retrovirus" because it can integrate its genetic material into key chromosomes within the body and replicate. Once it has made its mark within the chromosomes, it remains latent and becomes resilient to any form of treatment or attack.

In this way, the HIV virus is different from other retroviruses in that it has the ability to evade the body's natural defense systems. It also directly targets the cells that are responsible for the response to any viral pathogen, and has an uncanny ability to mutate frequently and quickly in response to any attempts made by the body's defense system.

Previous attempts at developing an HIV vaccine, despite passing Phase I of clinical trials, have failed to show any promise in the fight to find a cure for this resilient disease. A vaccine was tested by the National Institute of Allergy and Infectious Diseases (NIAID) and the New Jersey pharmaceutical company Merck & Co. - V520 - which was designed to stimulate HIV-specific cellular immunity.

In their STEP trial, which comprised of 3,000 participants from across the world, it was found that the vaccine might actually increase risk of HIV infection. Consequently, trials were discontinued on the advice of the Independent Data and Safety Monitoring Board (DSMB).

SAV001-H: activating the natural immune response

"Previous attempts at developing an HIV vaccine have failed to show promise in the fight to find a cure for this resilient disease."

The vaccine being tested by Canadian scientists is known as SAV001-H, which contains whole, killed HIV-1 and works in the same manner as similar vaccines used for influenza, rabies, polio and hepatitis A. Unlike the more traditional attempts to prevent the HIV virus, the SAV001-H vaccine works by activating the body's natural immune response to fight the virus.

The body's response to the HIV vaccine, like its response to other vaccines, is the activation of the immune system to produce antibodies specific to fighting the offending virus.

To date, it is the first time ever that scientists have used the whole virus to create a vaccination. Indeed, until now vaccines have been focused on using certain proteins or genes from the virus, but not the virus in its entirety. The whole virus used in SAV001-H is a derivative of the HIV-1 virus and has been genetically altered in such a way that it cannot cause HIV in someone who is injected with it. As a further precaution, to prevent possible infection, the virus is radiated and treated with chemicals.

Exceeding expectations: a HIV vaccine with no side effects

Preliminary findings for SAV001-H have not only shown promise, but have exceeded expectations. Phase I of the clinical trials was approved and commenced with a small sample of HIV positive volunteers located at two clinics within Los Angeles. A sample size of 40 men and women were assigned to groups, with eighteen receiving the vaccine and six receiving the placebo. None of the participants given the vaccine suffered any adverse effects.

"Preliminary findings for SAV001-H have exceeded expectations."

Furthermore, an increase in the body's defence cells was almost tenfold more than what researchers had anticipated.

To ensure there are no long-term reactions to participation in the trial, volunteers have been followed in six-month intervals, to check for any adverse symptoms.

No adverse side-effects have arisen, providing more credence to furthering clinical trials in efforts to pave the way for finding an effective treatment or, indeed, a cure for the HIV virus.

Lead scientist Dr Chil-Yong Kang, at the University of Western Ontario, Canada, says: "We are so excited about this interim report and are now proceeding with preparations for Phase II."

Advancing clinical trials: Phases II and III

"Phases II and III of SAV001-H trials are on the horizon; participants will be HIV negative volunteers who are at high risk."

Phases II and III of SAV001-H trials are on the horizon for 2013, when participants will be HIV negative volunteers who are at high risk for contracting the disease.

Phase II will comprise of a sample group of 600 and Phase III a much larger group of 6,000. The trials are set to be held in Canada, the United States and Europe, the rationale being that taking a cross-sectional group of individuals from different countries will enhance the rigour of any findings.

Whether Phases II and III continue to produce such positive findings remains to be seen. At best, the hope is that the trials will continue to demonstrate no adverse effects to participants.

Despite the limitations of clinical trials and some skepticism over the findings, Dr Kang remains confident, stating that: "We expect to get great news from volunteers in Phase II."

Tremendous promise

Not only did the SAV001-H vaccine have no adverse effects on trial participants, but it was also shown to significantly boost immunity in those it was administered to. This is the first ever trial to show promise in the fight against a disease that has persistently challenged the medical community.

Indeed, although ongoing research has made HIV less of a fatal disease and more of a chronic illness, the adverse consequences on those who have the disease remain devastating. It is, therefore, not surprising that the "tremendous promise" of developing a vaccine with no adverse effects, as offered by Dr Kang and his team, has sparked excited anticipation among the medical community. In the words of Dr Kang: "If we can eradicate HIV, or if we can prevent HIV infection, certainly that will be the happiest achievement I can accomplish."

---------------------------------------------------

HIV vaccine produces no adverse effects in trials

By Communications Staff September 03, 2013
http://communications.uwo.ca

Editor's note: Dr. Chil-Yong Kang of Western's Schulich School of Medicine & Dentistry will be online at 10 a.m. Friday, Sept. 6, answering questions about the Phase I clinical trial of the Sumagen AIDS vaccine as part of an Ask Me Anything (AMA) on Reddit.
http://www.sumagen.co.kr/english/business/aids_vaccine.htm

Photo by Paul Mayne

Developed by Dr. Chil-Yong Kang and his team at the Schulich School of Medicine & Dentistry, with the support of Sumagen Canada, the first and only preventative HIV vaccine based on a genetically modified killed whole virus (SAV001-H) holds tremendous promise for success in the final phases of clinical testing now that the first hurdle has been accomplished.
Phase I Clinical Trial (SAV CT 01) of the first and only preventative HIV vaccine based on a genetically modified killed whole virus (SAV001-H) has been successfully completed with no adverse effects in all patients, Western and Sumagen Canada Inc. announced today.
Developed by Dr. Chil-Yong Kang and his team at the Schulich School of Medicine & Dentistry, with the support of Sumagen Canada, the vaccine (SAV001-H) holds tremendous promise for success in the final phases of clinical testing now that the first hurdle has been accomplished. It is the only HIV vaccine developed in Canada currently in clinical trial, and one of only a few in the world.

This vaccine is the first genetically modified killed whole virus vaccine (SAV001-H) in human clinical trial to evaluate its safety, tolerability and immune responses. The human clinical trial was initiated in March 2012 and completed in August 2013. This trial was a randomized, observer-blinded, placebo-controlled study of killed whole HIV-1 vaccine (SAV001-H) following intramuscular (IM) administration. HIV-infected, asymptomatic men and women, 18-50 years of age, have been enrolled in this study and randomized into two treatment groups to administer killed whole HIV-1 vaccine (SAV001-H) or placebo. The adverse effects after vaccination were recorded on a volunteer diary card by the volunteers seven days after vaccination. Thereafter, the volunteers visited the test sites on Weeks 4, 6, 12, 18, 26 and 52 after vaccination and were analyzed for hematology, clinical chemistry, urinalysis and physical examination by principal investigators. No serious adverse event was observed in any volunteer vaccines throughout the observation periods.

In addition to safety evaluation, HIV-1 specific antibody detections have been performed throughout the follow up period. The antibody against p24 capsid antigen increased as much as 64-fold in some vaccines and antibody against gp120 surface antigen increased up to eight-fold after vaccination. The increased antibody titers were maintained during the 52 week study period. The boost antibody production in HIV-positive volunteer vaccines is highly encouraging, since it forecasts a success of the Phase 2 human clinical trial, which will measure the immune responses.

In particular, the antibody against gp120 surface antigen is considered to be very important, since some of these antibodies may represent the broadly neutralizing antibodies, which seem to be the most important parameter of an effective HIV vaccine for prevention of HIV-infection.

SAV001-H is the first genetically modified killed whole virus vaccine (SAV001-H) in human clinical trial and proving its safety was the major concern for going forward for next steps. With these encouraging results from the Phase I Clinical Trial, Sumagen is confident in developing SAV001-H as the first preventative HIV vaccine for saving millions of lives and is now preparing for the next phases of trials to show the immunogenicity and efficacy.

"Even though Sumagen has struggled and spent a much longer time to overcome manufacturing difficulties and to meet the USFDA's requirements, we have accomplished successfully Phase I Clinical Trial of SA001-H and proven that there is no safety concern of SAV001-H in human administration," said Jung-Gee Cho, Sumagen CEO. "We are now prepared to take the next steps towards Phase II and Phase III clinical trials. We are opening the gate to pharmaceutical companies, government, and charity organization for collaboration to be one step closer to the first commercialized HIV vaccine."

HIV/AIDS has killed 35 million people worldwide, and more than 34 million people currently live with the virus infection. Since the virus was characterized in 1983, there have been numerous trials through pharmaceutical companies and academic institutions around the world to develop vaccines; however, no vaccine has been successful to date. Other HIV vaccines evaluated through human clinical trials have focused on either one specific component of HIV as an antigen, genetic vaccine using recombinant DNA, or recombinant viruses carrying the HIV genes. Kang's vaccine is unique in that it uses a killed whole HIV-1, much like the killed whole virus vaccines for polio, influenza, rabies and hepatitis A. The HIV-1 is genetically engineered so it is safer and can be produced in large quantities.

Through WORLDiscoveries, Western's technology transfer office, Sumagen Canada has secured patents for the SAV001 vaccine in more than 70 countries, including the United States, European Union, China, India and South Korea. The vaccine has been manufactured at a bio-safety level 3 (BSL3) good manufacturing practice (GMP) facility in the United States.

--------------------

HIV/AIDS vaccine passes Phase 1 clinical trial in humans

Evan Ackerman
Wednesday, September 4, 2013
http://www.dvice.com

Human Testing

The clinical trial, which evaluated safety, tolerability, and immune responses, was initiated in March 2012 and completed in August 2013. The study of the vaccine, known as SAV001-H, followed intramuscular administration in HIV-infected, asymptomatic men and women, 18 to 50 years of age. The trial studied the vaccine's effects on volunteers as compared to a placebo group. After receiving the vaccination, volunteers visited test sites on weeks four, six, 12, 18, 26, and 52 for a general physical examination as well as analysis of clinical chemistry, hematology, and urinalysis. Researchers observed no serious adverse events and also found a surprising boost in antibody production, which may forecast success in Phase 2 trials measuring immune response. The antibody against p24 capsid antigen increased as much as 64-fold in some vaccinees while the antibody against gp120 surface antigen increased up to eight-fold. P24 is a structural protein that makes up most of the HIV viral core also known as the 'capsid.' High levels of p24 are present in the blood serum of newly infected individuals during the short period between infection and seroconversion, making p24 antigen assays useful in diagnosing primary HIV infection. A glycoprotein, gp120, is necessary for attachment to cell surface receptors and also allows for the HIV virus to enter cells.

The increased antibody titers were maintained during the 52-week study period. Production

SAV001-H, which was produced at a manufacturing facility in the U.S., is the only HIV vaccine developed in Canada and one of only a few in the world. Sumagen anticipates having the first HIV vaccine approved for market. HIV currently affects more than 34 million people who live with the virus worldwide, according to the World Health Organization. Over the past three decades, HIV has claimed more than 25 million lives.

Since the virus was characterized in 1983, pharmaceutical companies and academic institutions around the world have attempted, yet consistently failed, to develop a vaccine. What is unique about Kang's vaccine is its use of a killed-whole HIV-1, which is similar to the vaccines developed for polio, influenza, and rabies. HIV-1 is also genetically engineered; this raises its safety profile and the possibility of it being produced in large quantities. Sumagen is a member of Curo Group, a Seoul-based company with subsidiaries or affiliates in financial services, information technology, and other business areas. Sumagen has secured patents for the SAV001 vaccine in more than 70 countries, including the U.S., the European Union, China, India, and South Korea.

Development of Sumagen's HIV vaccine has been supported by the government of Canada as well as the Bill and Melinda Gates Foundation.

Sumagen, the South Korean biotech firm sponsoring the vaccine, cited manufacturing, as well as USFDA requirements as hurdles in bringing the vaccine to market, but, if all goes well in trials, it could be commercially available in five years.

"We are now prepared to take the next steps towards Phase II and Phase III clinical trials," CEO Jung-Gee Cho said in a press release.

\"We are opening the gate to pharmaceutical companies, government, and charity organization for collaboration to be one step closer to the first commercialized HIV vaccine."

Kang's vaccine is unique in that it uses a killed whole HIV-1, much like the killed whole virus vaccines for polio, influenza, rabies and hepatitis A. The HIV-1 is genetically engineered so it is non-pathogenic and can be produced in large quantities.

Through WORLDiscoveries, Western's technology transfer office, Sumagen Canada has secured patents for the SAV001 vaccine in more than 70 countries, including the U.S., the European Union, China, India and South Korea. The vaccine has been manufactured at a bio-safety level 3 (BSL3) good manufacturing practice (GMP) facility in the United States.

Located in The Stiller Centre for Technology Commercialization in Western's Research Park in London, Ontario, Sumagen Canada was established in 2008 specifically to manage and support clinical development of Kang's vaccine. Sumagen Canada is a subsidiary of Sumagen Co. Ltd., a Korean-based pharmaceutical venture company.

Source

Efficacy and safety of combination therapy of natural human interferon beta and ribavirin in chronic hepatitis C patients

Intern Med. 2011;50(19):2083-8. Epub 2011 Oct 1.

Arase Y, Suzuki Y, Suzuki F, Matsumoto N, Akuta N, Imai N, Seko Y, Sezaki H, Kawamura Y, Kobayashi M, Hosaka T, Saito S, Ikeda K, Kobayashi M, Kumada H.

Department of Hepatology and Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Japan. es9y-ars@asahi-net.or.jp

Abstract

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of combination therapy of natural human interferon-beta and ribavirin for patients for whom prior interferon therapy was discontinued due to depression induced by interferon-alpha.

METHODS: Inclusion criteria were as follows; 1) HCV-genotype 1b, 2) serum HCV RNA level of ≥100 KIU/mL, 3) stopping the prior interferon-alpha monotherapy or combination therapy of interferon-alpha and ribavirin due to the appearance of depression. A total of 14 were enrolled in this prospective cohort study. The treatment period of combination therapy was 48 weeks. Depression states, reflected by Beck depression inventories and Hamilton depression rating scale, were assessed during combination therapy. Nonparametric procedures were employed for the analysis of background features of the patients with sustained virological response (SVR) and without SVR. A p value of <0.05 was considered to indicate a significant difference.

RESULTS: Five of 14 patients (37.5%) had SVR by the intention to treat analysis. The SVR rate in patients who showed negative HCV RNA at 12 and 24 weeks after the initiation of combination therapy was 100% (4/4) and 83.3% (5/6), respectively. All of the patients continued the combination therapy owing to disappearance of severely adverse events contained the exacerbation of depression. Combination therapy did not yield a statistical difference in Beck depression inventories and Hamilton depression rating scale.

CONCLUSION: The combination therapy of IFN-beta and ribavirin is a possible therapy selection for the patients for whom interferon therapy was discontinued due to depression induced by interferon-alpha.

PMID: 21963723 [PubMed - indexed for MEDLINE]

View Full Text PDF [161K] (Free)

Natural Human IFN-β + Ribavirin Safe, Effective in Patients with Hepatitis C and Depression

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

467. Natural human interferon-beta plus ribavirin treatment toleration by chronic hepatitis C patients with depression or thrombocytopenia

Session: Poster Abstract Session: Prevention and Treatment of Viral Infections

Thursday, October 3, 2013

Room: The Moscone Center: Poster Hall C

Posters IDweek 2013 No467 ikezaki.pdf (275.6 kB)

Background: Natural human interferon-beta (nIFN-beta) seldom causes neurological adverse effects and is recommended for depressive patients with chronic hepatitis C. It also does not often cause thrombocytopenia, in contrast to pegylated interferon-alpha (PEG-IFN-alpha), which often causes thrombocytopenia. Limited data has been reported comparing nIFN-beta and PEG-IFN-alpha when ribavirin (RBV) is combined. This case-control study was done to compare the efficacy adverse effects of a combination of nIFN-beta or PEG-IFN-alpha plus RBV for chronic hepatitis C patients.

Methods: Sixty patients (42 hepatitis C virus genotype 1 and 18 genotype 2) were treated with nIFN-beta plus RBV (48 week course for genotype 1 and 24 week course for genotype 2). Of them, 23 (38.3%) suffered pre-treatment severe depression. Their data was compared with that of 60 age-, sex-, and genotype-matched patients who were treated with PEG-IFN-alpha plus RBV treatment for the same treatment periods. None of the patients in the PEG-IFN-alpha treated group suffered pre-treatment depression.

Results: Sustained virological response rates did not significantly differ between the nIFN-beta and PEG-IFN-alpha treated groups (genotype 1, 21.4 % vs. 33.3 %, P=0.328; genotype 2, 72.2 % vs. 88.9 %, respectively, P=0.402). None of the nIFN-beta-treated patients showed exacerbation of depression or malaise, but 7 (11.7%) of 60 PEG-IFN-alpha treated patients developed severe malaise. The mean percentage of platelet count decrease from baseline to the week 4 of treatment significantly differed between the nIFN-beta and PEG-IFN-alpha groups (-7.1% vs. -26.2%) (P<0.001). Among patients with a baseline platelet count <120×10⁹/L, the percentage of decrease to <80×10⁹/L at week 4 was significantly lower at 50.0% (14 of 28) of the nIFN-beta-treated group than at 88.9% (8 of 9) of the PEG-IFN-alpha-treated group (P=0.035).

Conclusion: nIFN-beta plus RBV treatment was well tolerated by chronic hepatitis C patients with depression or thrombocytopenia.

Hiroaki Ikezaki, MD., Norihiro Furusyo, MD., PhD., Satoshi Hiramine, MD., Eiichi Ogawa, MD., PhD., Masayuki Murata, MD., PhD. and Jun Hayashi, MD., PhD., Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan

Disclosures:

H. Ikezaki, None

N. Furusyo, None

S. Hiramine, None

E. Ogawa, None

M. Murata, None

J. Hayashi, None

Source

UAE aims to be hepatitis C free by 2020

Incidence in UAE is low but screenings must still be made, expert says

By Janice Ponce de Leon, Staff Reporter

Published: 20:00 October 5, 2013

Dubai: By 2020, the whole world aims to be hepatitis C free — and the UAE is on track on this front.

A liver disease which causes inflammation, liver scarring, and liver failure if left untreated, hepatitis C (HCV) affects about 150 million people around the globe according to the World Health Organisation. Of this number, more than 350,000 people die every year from hepatitis C-related liver diseases.

In the UAE, the incidence of HCV is low but screenings must still be made in order to get proper treatment for the disease dubbed the silent killer for it is usually asymptomatic.

“We don’t have a big problem of hepatitis C in the UAE. With the genotype 1 [of HCV], which is predominant among UAE nationals, the treatment is promising and we have treated a large number of patients and the response is more than 70 per cent with the new drug. We hope by 2020 we can eradicate the virus from UAE nationals,” Dr Salem Awadh, consultant gastroenterologist and former president of the Emirates Gastroenterology Society, told Gulf News on the sidelines of the Media Academy on Hepatitis C in the Middle East on Saturday. The academy was sponsored by MSD, a global health-care company that works to create vaccines and treatment options for many diseases, including HCV.

Based on a MSD-PharmARC study in 2011, a total of 642 cases of HCV have been reported in the UAE with Dubai reporting 278 cases and Abu Dhabi 204 cases. Of this number, 70 per cent are expatriates – with Egyptians representing the largest number, followed by Pakistanis. The remaining 30 per cent are UAE nationals.

“These are UAE nationals who received blood transfusion before 1991. At that time we didn’t know the virus and we were importing blood from outside, mainly from the US and Europe where genotype 1 is the most common,” Dr Awadh said.

HCV is transmitted through contact with an infected blood of another person.

With new treatment options currently being studied and soon to be introduced in the market, Dr Awadh is optimistic that old carriers of HCV will soon be treated. The focus can shift on newly detected cases among UAE nationals who transmit HCV through needle-sharing.

“We are detecting new young patients, young generations of patients between 25 and 40 who have been using IV or intravenous drugs [illegal drugs administered through the veins], who are UAE nationals and these people need to be counselled. We have a big rehabilitation centre in Abu Dhabi for which these people are admitted and they are treated,” Dr Awadh said.

HCV treatment for UAE nationals is free while expatriates who are HCV positive may seek treatment through different non-government organisations.

Meanwhile, other countries in the MENA region, especially Egypt, with high prevalence rates of HCV are campaigning for international and local cooperation in order to rid the country of HCV. Access to affordable treatment options are also needed, Dr Hesham Rafaat Mohammad Al Khayat, of the Theodor Bilharz Research Institute in Egypt, said.

Source

Hospitalized HIV patients benefit from seeing infectious diseases specialists

Public release date: 3-Oct-2013

Contact: Lauren Brush
lbrush@pcipr.com
415-978-3601
Infectious Diseases Society of America

Medication errors more than twice as likely to be resolved

SAN FRANCISCO – When patients with HIV are hospitalized for other conditions, such as a heart problem, surgery or complications of diabetes, mistakes are often made involving their complicated anti-retroviral therapy (ART) regimens. But those errors are more than twice as likely to be corrected when patients are seen by an infectious diseases (ID) physician, suggests a Cleveland Clinic study being presented at IDWeek 2013™ today.

Most patients with HIV are cared for by physicians with HIV expertise in the community, and when they are hospitalized for non-HIV conditions, hospital providers who are unfamiliar with the complexities of HIV therapy may make errors that have an impact on their treatment, from prescribing medications that negatively interact with their ART regimens to providing the wrong dose of medication. The study found those errors can be reduced by employing a variety of interventions, including education, modification of the electronic drug file to help guide the accurate prescribing of medications, and daily medication profile review by a pharmacist specializing in HIV.

Additionally, researchers found involving an infectious diseases physician is key in improving hospital care: Errors were corrected in 68 percent of patients who saw an ID specialist vs. 32 percent of those who did not.

"Most HIV care has shifted from inpatient to outpatient, so hospital providers aren't as familiar with complicated ART regimens – and as a result, medication errors are common," said Elizabeth A. Neuner, PharmD, an ID clinical pharmacist at Cleveland Clinic and lead author of the study. "By enacting a multidisciplinary plan including pharmacists and physicians to prevent errors from happening or correcting them if they did, we were able to significantly reduce errors in ART medications."

In the two-part study, researchers looked at 162 patients with HIV who were treated in the hospital before the interventions were put in place, and 110 patients who were treated after changes were made. Errors – meaning guideline recommendations weren't followed – were made 50 percent of the time before interventions were put in place and 34 percent of time time after. When errors were made, they were resolved 36 percent in the pre-interventions group and 74 percent of the time in the interventions group. Errors were corrected much more quickly in the intervention group: an average of 23 hours, vs. 180 hours in the pre-intervention group.

Corrections varied, for example: prescribing accurate ART medication and dosage; adjusting the regimen because a new medication (such as for heart problems or diabetes) was interacting with one of the ART medications; and revising the therapy due to address a new problem, such as kidney injury. In some cases, physicians opted not to correct the error because the patient was doing well on the therapy and the benefits outweighed the risks.

ART regimens often involve a combination of three or more medications that are taken several times a day.

ID specialists identified medication errors and resolved them such as by changing the dose or frequency of medication, or adding a medication that was missing, said Dr. Neuner.

###

Co-authors of the study being presented at IDWeek by Dr. Neuner are Jamie Sanders, PharmD, Andrea Pallotta, PharmD, Seth Bauer, PharmD, Jennifer Sekeres, PharmD, Ramona Davis, PharmD and Alan Taege, MD.

About IDWeek

IDWeek 2013™ is an annual meeting of the Infectious Diseases Society of America (IDSA), the Society for Healthcare Epidemiology of America (SHEA), the HIV Medicine Association (HIVMA) and the Pediatric Infectious Diseases Society (PIDS). With the theme "Advancing Science, Improving Care," IDWeek features the latest science and bench-to-bedside approaches in prevention, diagnosis, treatment, and epidemiology of infectious diseases, including HIV, across the lifespan. IDWeek 2013 takes place October 2-6 at the Moscone Center in San Francisco. For more information, visit http://www.idweek.org, follow us on Twitter @IDWeek2013 or like us on Facebook at IDWeek.

Source

Speak Out: Let's Bring HIV Out of the Closet

New Campaign from Greater Than AIDS developed locally with the San Francisco Department of Public Health to Engage Gay and Bisexual Men in Response to HIV/AIDS

SAN FRANCISCO, Oct. 4, 2013 /PRNewswire/ -- Greater Than AIDS, a leading national public information response to the domestic epidemic, today launched Speak Out, a new campaign developed locally with the San Francisco Department of Public Health to engage gay and bisexual men in response to HIV/AIDS and confront the silence and stigma that too often surrounds the disease.   An overarching theme of the cross-platform campaign is to encourage more open communication about HIV in relationships, with health care providers and within the community generally. 

In a provocative series of outdoor ads that begin appearing around the city this month, including a media "take over" of the Castro MUNI station, a diverse group of gay men, both positive and negative, open up about HIV in the gay community and why it continues to be so hard to talk about.  With the tagline, "What You Say Matters," the men's unvarnished comments bring attention to the stigma and silence that too often still surrounds HIV. 

In "Let's Bring HIV Out of the Closet," an online signature video produced for the campaign, the men open up about how HIV has affected their lives and those around them.  In this intimate and candid conversation, the men talk about the growing silence about HIV, the stigma that exists within the gay community around the disease and what needs to happen to address it.  The video is being distributed on the web and through social media and promoted through other elements of the campaign.

"Speak Out is about bringing the energy and momentum of the gay movement to bear once again on HIV/AIDS," said Tina Hoff, Senior Vice President and Director of Health Communications and Media Partnership, Kaiser Family Foundation, a founding partner of Greater Than AIDS.  "More than 30 years since the epidemic began gay and bisexual men continue to be among those most affected by HIV.  It doesn't have to be this way."

Through targeted media messages and complementary community outreach, Speak Out encourages more open communication about HIV in all aspects of life, including:  

• SPEAK OUT For Our Relationships. Talking with friends and lovers about HIV, including using protection, getting tested together, and discussing HIV status.
• SPEAK OUT For Our Health.  Asking to be tested, talking about treatment options and seeking support when needed.
• SPEAK OUT For Our Community.  Confronting stigma and addressing misconceptions through open communication with the people in our lives. 

"Speak Out is an opportunity to engage the Gay community to speak out around knowing their status, the importance of getting tested at least every six months, and getting into care and treatment". It is about finding our voice again in our community to ensure that we all find an healthy way to take care of ourselves,"  Vincent Fuqua, Health Program Coordinator, SFDPH, Community Health Equity and Promotion.

Nationally, gay and bisexual men account for the majority (56%) of the more than 1.1 million people living with HIV today in the U.S., and two thirds (66%) of new HIV infections.  In San Francisco, gay and bisexual men account for an even greater share of the local epidemic, representing 88% of all persons living with HIV in the city and 82% of new infections.  

Whether HIV positive or negative, the campaign stresses the role of the community as a whole in addressing HIV/AIDS, including promoting increased routine testing  for gay men as recommended by the San Francisco Department of Health and linkage to care and treatment. 

---------------------------------------------------

SF>AIDS.  While San Francisco is leading the nation on many indicators, the overall rate of new infections among gay and bisexual men (referred to as men who have sex with men or MSM) is still very high and HIV remains a serious threat for MSM in the city.  As of 2011, overall HIV prevalence among the share of MSM who do not inject drugs is estimated at more than one in five (22.7%).     

Testing rates have been increasing in San Francisco according to recent data, yet still many MSM in the city are not being tested as routinely as recommended(every 3-6 months).  According to a 2011 survey, 40% of sexually active MSM who were not already diagnosed as HIV positive in San Francisco had not been tested in the previous 6 months.  Also of concern is the share of men who are HIV positive who are not in care and on treatment following diagnosis.  Only half of HIV cases reported in San Francisco between 2008 and 2010 had viral suppression within one year of diagnosis. 

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For more information about Greater Than AIDS and the Speak Out campaign, visit:  www.greaterthan.org/speakout.

About Greater Than AIDS
Greater Than AIDS is a leading national public information response focused on the U.S. domestic epidemic. Launched in 2009, it is supported by a broad coalition of public and private sector partners, including: major media and other business leaders; Federal, state and local health agencies and departments; national leadership groups; AIDS service and other community organizations; and foundations, among others.

Through targeted media messages and community outreach, Greater Than AIDS works to increase knowledge, reduce stigma and promote actions to stem the spread of the disease.  While national in scope, Greater Than AIDS focuses on communities most affected.

The Kaiser Family Foundation – a leader in health policy and communication – provides strategic direction and day-to-day management, as well as oversees the production of the campaigns.  The Black AIDS Institute – a think tank exclusively focused on AIDS in Black America – provides leadership and expert guidance and supports community engagement.  Additional financial and substantive support is provided by the Elton John AIDS Foundation, Ford Foundation and MAC AIDS, among others.  

SOURCE Greater Than AIDS

Source

VIDEO: New treatments transform HCV management

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

Provided by Healio

October 3, 2013

SAN FRANCISCO — Michael S. Saag, MD, of the University of Alabama at Birmingham, discusses the revolution in HCV treatments that have transformed the disease from a chronic infection with serious complications to a manageable and potentially curable condition.

Disclosures: Saag reports financial relationships with Bristol-Myers Squibb, Merck, Gilead, ViiV Healthcare, Abbvie, Boehringer Ingelheimand Pharmaceuticals and Janssen.

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Sofosbuvir and Peginterferon alfa-2a/RibavirinTreatment of naïve Genotype 1-4 HCV infected patients that are co-infected with HIV

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

714. Sofosbuvir and Peginterferon alfa-2a/RibavirinTreatment of naïve Genotype 1-4 HCV infected patients that are co-infected with HIV

Session: Poster Abstract Session: Antimicrobials: Novel Agents

Friday, October 4, 2013

Room: The Moscone Center: Poster Hall C

Posters Rodriguez IDWeek 88x44@275%-Final.pdf (66.1 kB)

Background: HIV/HCV co-infected patients are in need of safe and effective HCV treatments without risk for resistance and that can be given with antiretroviral treatment (ART). The efficacy and safety of the once daily, oral HCV NS5B inhibitor sofosbuvir in combination with peginterferon alfa-2a (peg-IFN) and ribavirin (RBV) for 12 weeks, was examined in a pilot study of HCV treatment-naive HCV/HIV-coinfected patients.

Methods: Twenty-three naïve, non-cirrhotic genotype 1-4 HCV/HIV co-infected patients received sofosbuvir 400mg QD, RBV 1000-1200 mg/day,and peg-IFN 180 μg/week for 12 weeks. Patients were required to be on stable ART with HIV RNA suppression.  The primary efficacy endpoint was SVR12 and safety assessments included HIV RNA and CD4 T-cell counts/percentages.

Results: Baseline characteristics of the study population and stable ART regimens are shown in the table.  Most patients had rapid on-treatment HCV RNA suppression; 22/23 (96%) had Week 2 HCV RNA below the limit of quantification, and there was no virologic breakthrough during therapy. Of the 12 patients to complete therapy to date, 10 (83%) achieved SVR4.   The most frequently reported AEs (>10%) were fatigue (30%), anemia (30%), and thrombocytopenia (17%).   No HIV viral breakthrough or reductions in CD4 T-cell percent occurred.  Complete HCV SVR12 results for all patients will be presented.

Conclusion: Treatment with sofosbuvir, peg-IFN and RBV for 12 weeks achieves high SVR-4 in this pilot trial in genotype 1-4, HCV treatment-naïve HCV/HIV co-infected patients. Therapy was well tolerated, without evidence of HIV viral breakthrough or changes in CD4 T-cell percent.

Baseline Characteristics (N=23)	Sofosbuvir + peg-IFN + RBV
Male, n (%)	18 (78)
Black, n (%)	8 (35)
IL28b CC genotype, n (%)	5 (22)
HCV Genotype, n (%)	19 (83)
1a	15 (65)
1b	4 (17)
2b	1 (4)
3a	2 (9)
4a/4b/4c	1 (4)
Log10 HCV RNA (IU/mL), mean (SD)	6.59 (0.87)
CD4 T-cell count (cells/μl), mean (SD)	562 (302)
CD4 T-cell percent, mean (SD)	28.8 (9.7)
ARV Regimen (N=23): Tenofovir/Emtricitabine PLUS
Efavirenz, n (%)	10 (43)
Ritonovir/Atazanavir, n (%)	8 (35)
Ritonovir/Raltegravir, n (%)	7 (30)
Ritonovir/Darunavir, n (%)	6 (26)
Rilpilvirine, n (%)	1 (4)
SVR4, n/N (%)	10/12 (83)

Maribel Rodriguez-Torres, MD¹, Jose Rodriguez-Orengo, PhD², Anuj Gaggar, MD, PhD³, William Symonds, PharmD³, John Mchutchison, MD³ and Milagros Gonzalez, MD⁴, (1)Gastroenterology, Fundacion de Investigacion, Rio Piedras, PR, (2)Biochemistry, University of Puerto Rico, San Juan, PR, (3)Gilead Sciences, Foster City, CA, (4)Fundacion de Investigacion, Rio Piedras, PR

Disclosures:

M. Rodriguez-Torres, None

J. Rodriguez-Orengo, None

A. Gaggar, Gilead Sciences: Employee, Salary

W. Symonds, Gilead Sciences: Employee,

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Transmission of Hepatitis C Virus from an Organ Donor with Undetectable Viremia by Nucleic Acid Testing

Infectious Disease Week (IDWeek)
October 2-6, 2013
San Francisco, Ca

630. Transmission of Hepatitis C Virus from an Organ Donor with Undetectable Viremia by Nucleic Acid Testing

Session: Oral Abstract Session: Infections in Transplantations and Immunocompromised

Friday, October 4, 2013: 9:30 AM

Room: The Moscone Center: 220-226

Background: Nucleic acid testing (NAT) is used for screening hepatitis C virus (HCV) infection among solid organ donors. On March 9, 2012 two organ recipients were reported to the Centers for Disease Control and Prevention with newly diagnosed HCV infections on routine post-transplant screening. Despite active injection drug use (IDU), the donor had undetectable HCV by polymerase chain reaction (PCR) testing. A public health investigation was initiated to determine the sources of HCV transmission.

Methods: The following donor and recipient specimens were tested by RNA quantitative PCR for HCV: donor’s serum, donor splenocytes from organ recovery; and recipients’ pre-and post-transplant serum. HCV genomic sequencing and quasispecies analysis were used to measure relatedness of HCV. Medical records were reviewed and recipients were interviewed for HCV-related risk factors. Epidemiologic investigations into source of transmission included assessment of healthcare exposures. 

Results: HCV RNA was undetectable by PCR and anti-HCV was negative by enzyme immunoassay on donor serum, but HCV genotype 2b was isolated from donor splenocytes procured at organ recovery, 4 days after serum collection. HCV genotype 2b was newly isolated by PCR in the left kidney recipient (day 9 post-transplant) and the heart recipient (day 30 post-transplant); two other recipients had chronic HCV infection before transplant. Quasispecies analysis showed close relatedness between HCV strains from the left kidney and heart recipients, indicating a common source; comparison to the donor’s HCV strains is ongoing. The donor’s IDU and recent plasma transfusion were identified as HCV-related risks. Trace-back of transfused units is ongoing; no other sources have been identified.

Conclusion: We report the first known transmission of HCV infection from an organ donor with negative screening by NAT, indicating very recent donor infection. These findings highlight the importance of communicating transmission risk to recipients, despite the most sensitive available donor screening. Donor-derived transmission of HCV and standardized recipient follow-up testing should be considered in recipients of organs procured from donors with behavioral risks for blood-borne pathogens.

Anil Suryaprasad, MD¹, Susan N. Hocevar, MD², Lauren Torso, MPH³, Jan Drobeniuc, MD, PhD¹, Yury Khudyakov, PhD¹, David Pegues, MD, FIDSA, FSHEA⁴, Matthew J. Kuehnert, MD, FIDSA² and Emily Blumberg, MD, FIDSA⁵, (1)Division of Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA, (2)Division of Healthcare Quality and Promotion, Office of Blood, Organ, and Other Tissue Safety, Centers for Disease Control and Prevention, Atlanta, GA, (3)Pennsylvania Department of Health, Harrisburg, PA, (4)University of Pennsylvania Health System, Philadelphia, PA, (5)Medicine, University of Pennsylvania Health System, Philadelphia, PA

Disclosures:

A. Suryaprasad, None

S. N. Hocevar, None

L. Torso, None

J. Drobeniuc, None

Y. Khudyakov, None

D. Pegues, None

M. J. Kuehnert, None

E. Blumberg, None

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New injection device delivers optimum treatment dose to hepatitis C patients

Published on October 5, 2013 at 8:17 AM

A new injection device, ViraferonPeg Clearclick, has launched in the UK today for hepatitis C patients to accurately titrate and self-administer their weekly dose of ViraferonPeg (peginterferon alfa-2b).

The device has been specially designed to maintain dosing flexibility, across five dosage strengths (50 mcg/0.5 mL, 80 mcg/0.5 mL, 100 mcg/0.5 mL, 120 mcg/0.5 mL and 150 mcg/0.5 mL) helping nurses and patients to deliver the optimal dose and help maximise patient outcomes.

Clearclick will replace the existing Redipen and offer a number of additional features such as clearer markings and audible feedback to confirm that the proper dose has been injected  as well as an ergonomic design and needle shield to help patients safely and accurately administer a dose.

Hazel Allen, Senior Clinical Nurse Specialist in Hepatology, The Royal Bournemouth and Christchurch Hospital, said “The Clearclick pen is an easier-to-use device which allows for small incremental changes in treatment titration, making it simpler for patients to get the optimum treatment dose. This is particularly important for harder-to-treat patients, such as those with advanced liver disease, where the right dosage is so important to help minimise the side effects whilst at the same time maximising the chance of response.”

Peginterferon alfa-2b is a once-weekly interferon product. In combination with ribavirin and boceprevir (tritherapy), it is indicated for the treatment of chronic hepatitis C (CHC) genotype 1 infection in adult patients (18 years of age and older) with compensated liver disease who are previously untreated or who have failed previous therapy.

Peginterferon alfa-2b is indicated for the treatment of adult patients (18 years of age and older) with CHC who are positive for hepatitis C virus RNA (HCV-RNA), including patients with compensated cirrhosis and/or co-infected with clinically stable HIV (see section 4.4).

Peginterferon alfa-2b in combination with ribavirin (bitherapy) is indicated for the treatment of CHC infection in adult patients who are previously untreated including patients with clinically stable HIV co-infection and in adult patients who have failed previous treatment with interferon alpha (pegylated or nonpegylated) and ribavirin combination therapy or interferon alpha monotherapy

Peginterferon alfa-2b is indicated in a combination regimen with ribavirin for the treatment of children 3 years of age and older and adolescents, who have chronic hepatitis C, not previously treated, without liver decompensation, and who are positive for HCV-RNA.

ViraferonPeg Clearclick was approved by the European Medicines Agency (EMA) in May 2013 and is now available for use in the UK.

Source: http://www.msd-uk.com/

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