Patients in Transition

Avoiding Detours on the Road to HIV Treatment Success

Baligh R. Yehia, Shreya Kangovi, Ian Frank

AIDS. 2013;27(10):1529-1533.

Introduction

To fully benefit from antiretroviral therapy (ART), people living with HIV (PLWH) need to be aware of their HIV infection, linked to and engaged in regular HIV care, and must receive and adhere to ART.^[1,2] Completion of all these steps is often unsuccessful, with only 28% of all PLWH in United States achieving viral suppression.^[3] Our current understanding for improving health behaviors (linkage to care, retention in care, ART receipt and adherence) and outcomes (viral suppression, prevention of AIDS-defining conditions, transmission of HIV, and survival) relies on modifying patient and environmental factors.^[1] (Fig. 1) However, this framework is static and does not account for patients in transition.

Figure 1.

Revised behavioral model for people living with HIV. Adapted from [1].

Helping patients negotiate transitions is essential for HIV treatment success. Transitions of care are defined as the movement of patients between different levels of care, healthcare locations, or providers. They can occur within the same setting (e.g. hospital) or between settings (e.g. hospital to outpatient care), and usually represent changes in health status or social state.^[4–6] Transitions are inherently difficult for patients, but are particularly challenging for PLWH who face high rates of poverty, mental illness, and confront HIV-related stigma and discrimination.^[7] Emerging data suggests that transitions of care are important determinants of patient behaviors and outcomes.^[8–12]

Transitions of Care Impact Health Behaviors and Outcomes

For PLWH, commonly encountered transitions include transfers from inpatient to outpatient care, correctional institution to community-based care, and pediatric/adolescent to adult clinic. HIV-infected patients are at increased risk of medication errors when transitioning from inpatient to outpatient care given their complex medication regimens, multiple comorbidities, and interactions with inpatient providers who may lack experience with HIV infection and ART.^[13] Direct communication between hospital physicians and primary care providers occur in only 3–30% of all hospital discharges, and discharge summaries are infrequently available at the time of first postdischarge visit.^[14] This lack of communication may lead to ART medication errors and unrecognized drug–drug interactions, resulting in harmful side effects, development of drug resistance, and treatment discontinuation.^[13]

In transitioning from correctional institution to community-based care, released inmates must contend with a variety of new concerns, including reconnecting with family, securing housing and employment, obtaining health insurance, and establishing outpatient HIV care.^[15] These sudden shifts in socioeconomic and healthcare factors compromise health outcomes for many PLWH transitioning from prison back to the community.^[8,9] Among 2115 HIV-infected inmates on therapy, only 18% fill an initial prescription for ART within 30 days of release, and 30% within 60 days.^[8] Reincarcerated PLWH who were on ART prior to release experienced a decrease in CD4 cell count by 80 cell/μl and an increase in HIV viral load by 1.14 log₁₀ copies/ml compared to their last recorded prison measure.^[9]

Adolescents and young adults transitioning from pediatric/adolescent to adult HIV care face changes in delivery of care, health information, and developmental stage. Youth living with HIV are accustomed to an interdisciplinary approach to care.^[5] This contrasts with the adult care model, where medical, mental health, and social services are often fragmented, requiring more independent navigation of the healthcare system. Youth in transition must also confront the discrimination, stigma, and fear associated with disclosing their HIV status to new providers and other patients.^[16] Among a cohort of young adults transitioning from pediatric/adolescent to adult care, immune function trended downward, 45% of patients reported that the transition was more difficult than expected, and 32% could not find emotional support services.^[10] Lastly, adult care necessitates more autonomous, self-directed management of HIV infection compared with pediatric/adolescent care. Many pediatric programs utilize unique adherence tools such as mobile phone short message service (text messaging) to encourage compliance with HIV care and treatment.^[17] Loss of this, and other support, may compromise retention in care and adherence to therapy for patients with differing levels of developmental readiness to transition.

The Dynamic Behavioral Model

To account for the effects of care transitions on health behaviors and outcomes, we introduce the Dynamic Behavioral Model. (Fig. 2) This new framework differs from prior models in several ways. First, it illustrates the interconnected relationship between patient and environmental factors. Many factors (e.g. transportation issues, availability and use of mental health services, and patient-provider concordance) do not belong in one domain, but rather involve both the patient and their environment. Second, this model highlights key factors which change as patients move from one care setting to another, namely socioeconomic status, access to care, developmental stage, health information, and delivery of care. Capturing this change is critical, because the relative difference between factors may be as important as the absolute state. For example, among 159 934 adult respondents to the 2004–2009 National Health Interview Survey, newly uninsured individuals were almost twice as likely to use emergency care services compared with continuously uninsured adults.^[18] This change in access to care (i.e. losing insurance) had a greater impact on patient behavior than no change at all. Lastly, the Dynamic Behavioral Model provides a framework for understanding the movement of PLWH between differing healthcare settings and can be used as a tool to help manage transitions in care.

Figure 2.

Dynamic behavioral model for people living with HIV.

Managing Healthcare Transitions for People Living With HIV

Successful transitions require all stakeholders – patients, providers, and caregivers – to anticipate future challenges and develop feasible solutions (). Changes in socioeconomic status (e.g. loss of housing, employment, or financial resources) and access to care (e.g. loss of insurance or primary provider) are commonly encountered by patients transitioning from one setting to another. Case management and patient navigation, employing community health workers to support and guide patients through the healthcare system, are effective at decreasing some of these obstacles to care.^[19] Among 437 HIV-infected patients with housing, insurance, and structural barriers to care, patient navigation increased the proportion of patients with an undetectable viral load by 50% and the proportion of patients retained in care by 15%.^[19] Utilizing social support services during transitions may help patients address changes in socioeconomic status or access to care.

Table 1.  Challenges and potential solutions for HIV-infected patients in transition.

Transition domain	Changes between care settings	Examples	Potential solutions
Socioeconomic status	Housing Employment	Prisoner needs to find housing upon release.	Address any competing needs (lack of housing, insurance, or social support) in conjunction with social workers and case managers.
Development	Developmental stage	Adolescent transitioning from pediatric/adolescent to adult care must manage HIV infection alone.	Provide developmentally appropriate coaching for self-care prior to transitions.
			Arrange a pretransfer visit where a receiving team member meets with the patient and the sending team prior to transfer and explains care delivery in the new setting.
Access to care	Health insurance HIV provider HIV medications	Prisoner needs to obtain insurance for antiretroviral therapy and to reestablish primary care.	Utilize social workers to help obtain health insurance.
			Employ patient navigators to assist in arranging outpatient appointments and to ensure adherence to care.
Health information	Medications Treatment plan Disclosure of HIV status to new individuals/providers	Inpatient providers need to communicate changes in antiretroviral and prophylaxis medications to outpatient providers.	Sending team includes relevant data elements in transfer summary, such as changes to medications.
Delivery of care	Level of patient autonomy Integration of services Support services	Community-based healthcare is more fragmented than institutional-based healthcare, necessitating independent navigation of the healthcare system.	Use pretransfer visits and patient navigators to help individuals adjust to and navigate the new healthcare environment

Assessing patient readiness, promoting medical independence, and engaging caregivers are considered critical elements to successfully transitioning youth from pediatric/adolescent to adult HIV care.^[5,10,16,20] New tools are needed to help providers manage the developmental aspects of care transitions. Specifically, programs aimed at assisting adolescent patients in developing the necessary skills for independently managing their own healthcare.

Effective transfer of health information is necessary for a successful care transition. The sending team must communicate relevant, accurate, timely, and patient-centered information, whereas the receiving team is responsible for assimilating this information and continuing the plan of care.^[4] When transferring patients with HIV infection, providers should remember to include: current medications and drug allergies, the most recent CD4 cell count and HIV viral load, history of opportunistic infections, documentation of resistance viruses, hepatitis coinfection status, and an assessment of the social situation, as these are important for receiving team providers starting or altering ART. Disclosure of HIV status is a unique and dynamic piece of health information that concerns both patients and providers. During a transition, many patients are anxious or fearful of disclosing their HIV status to new providers and other patients.^[16] Information on individuals who are aware or unaware of a patient's HIV infection should be communicated to prevent unwanted disclosure of HIV status. Healthcare organizations and providers should standardize the information necessary for transfer and leverage health information technology to optimize secure information exchange.

As patients move between healthcare settings, the delivery of care often changes. This may take the form of decreased support services and care integration, change in provider type and practice style, and the necessity of increased patient autonomy. Providers must be aware of these changes and prepare patients for the transition. This may involve incorporating a 'pretransfer visit,' where a receiving team member meets with the patient and the sending team prior to transfer; employing transitional care managers, advanced care nurses who care for the patient with the primary provider for a period of time posttransfer; or utilizing patient navigators.^[6]

Conclusion

HIV-infected individuals are particularly vulnerable during periods of transition. The Dynamic Behavioral Model provides a framework for understating how changes in socioeconomic status, development stage, access to care, health information, and delivery of care influence health behaviors and outcomes. Providers, healthcare organizations, and payers should no longer view patients as static individuals confined to a particular health setting, but rather consider them as part a care continuum transferring between settings and providers with continuous management. Focusing on healthcare transitions may provide additional strategies for improving engagement in care and clinical outcomes.

References

1. Ulett KB, Willig JH, Lin HY, Routman JS, Abroms S, Allison J, et al. The therapeutic implications of timely linkage and early retention in HIV care. AIDS Patient Care STDS 2009; 23:41–49.

2. Gardner EM, McLees MP, Steiner JF, Del Rio C, Burman WJ. The spectrum of engagement in HIV care and its relevance to test-and-treat strateges for prevention of HIV infection. Clin Infect Dis 2011; 52:793–800.

3. Centers for Disease Control and Prevention. Vital signs: HIV Prevention Through Care and Treatment - United States. MorbMortal Wkly Rep 2011; 60:1618–1623.

4. Coleman EA, Fox PD, Workgroup obotHCM. One patient, many places: managing healthcare transitions, Part I: introduction, accountability, information for patients in transition. Ann Longterm Care 2004; 12:25–32.

5. Reiss JG, Gibson RW, Walker LR. Healthcare transition: youth, family, and provider perspectives. Pediatrics 2005; 115:112–120.

6. Coleman EA, Fox PD, Workgroup obotHCM. One patient, many places: managing healthcare transitions, Part I: introduction, accountability, information for patients in transition. Ann Longterm Care 2004; 12:14–16.

7. Denning P, DiNenno E. Communities in crisis: is there a generalized HIV epidemic in impoverished urban areas of the United States? In: XVIII Interntional AIDS Conference Vienna, Austria; 2010.

8. Baillargeon J, Giordano TP, Rich JD, Wu ZH, Wells K, Pollock BH, et al. Accessing antiretroviral therapy following release from prison. JAMA 2009; 301:848–857.

9. Springer SA, Pesanti E, Hodges J, Macura T, Doros G, Altice FL. Effectiveness of antiretroviral therapy among HIV-infected prisoners: reincarceration and the lack of sustained benefit after release to the community. Clin Infect Dis 2004; 38:1754–1760.

10. Wiener LS, Kohrt BA, Battles HB, Pao M. The HIV experience: youth identified barriers for transitioning from pediatric to adult care. J Pediatr Psychol 2011; 36:141–154.

11. Yehia BR, Long JA, Stearns CR, French B, Tebas P, Frank I. Impact of transitioning from HIV clinical trials to routine medical care on clinical outcomes and patient perceptions. AIDS Care 2012; 24:769–777.

12. Bodenheimer T. Coordinating care: a perilous journey through the healthcare system. N Engl J Med 2008; 358:1064–1071.

13. Yehia BR, Mehta JM, Ciuffetelli D, Moore RD, Pham PA, Metlay JP, et al. Antiretroviral medication errors remain high but are quickly corrected among hospitalized HIV-infected adults. Clin Infect Dis 2012; 55:593–599.

14. Kripalani S, LeFevre F, Phillips CO, Williams MV, Basaviah P,

15. Baker DW. Deficits in communication and information transfer between hospital-based and primary care physicians: implications for patient safety and continuity of care. JAMA 2007; 297:831–841.

16. Baillargeon J, Binswanger IA, Penn JV, Williams BA, Murray OJ. Psychiatric disorders and repeat incarcerations: the revolving prison door. Am J Psychiatry 2009; 166:103–109.

17. Dowshen N, D'Angelo L. Healthcare transition for youth living with HIV/AIDS. Pediatrics 2011; 128:762–771.

18. Dowshen N, Kuhns LM, Johnson A, Holoyda BJ, Garofalo R. Improving adherence to antiretroviral therapy for youth living with HIV/AIDS: a pilot study using personalized, interactive, daily text message reminders. J Med Internet Res 2012; 14:e51.

19. Ginde AA, Lowe RA, Wiler JL. Health insurance status change and emergency department use among US adults. Arch Int Med 2012; 172:642–647.

20. Bradford JB, Coleman S, Cunningham W. HIV System Navigation: an emerging model to improve HIV care access. AIDS Patient Care STDs 2007; 21 (Suppl 1):S49–S58.

21. Fair CD, Sullivan K, Gatto A. Best practices in transitioning youth with HIV: perspectives of pediatric and adult infectious disease care providers. Psychol Health Med 2010; 15:515–527.

Acknowledgements
B.R.Y. developed the concept and drafted the manuscript. S.K. drafted the manuscript and provided critical revisions. I.F. provided critical revisions, administrative support, and study supervision.
This work was support, in part, by the Penn Center for AIDS Research, P30 AI 045008. B.R.Y. was supported by the National Institutes of Health (K23-MH097647-01A1).

AIDS. 2013;27(10):1529-1533. © 2013 Lippincott Williams & Wilkins

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Black Market for HIV Antiretroviral Drugs Booming

Medscape Medical News > Conference News

Neil Canavan

Jul 10, 2013

KUALA LUMPUR, Malaysia — A disturbing number of men with legal access to antiretroviral medications are selling their prescriptions on the black market, according to new research.

These diverted medications mean an increase in the ongoing risk for HIV transmission and treatment failure because of resistance to therapy in those who become infected.

"We started receiving law enforcement reports about drug diversions around 5 years ago from major cities in the United States," said Steven Kurtz, PhD, from the Center for Applied Research on Substance Use and Health Disparities in Coral Gables, Florida. "It quickly became clear that street markets had developed for antiretroviral medications."

A previous study looking at this problem in impoverished men found a diversion rate as high as 20%. What Dr. Kurtz and his team set out to establish in their investigation was the extent of diversion practices in men who have sex with men.

Dr. Kurtz presented the research here at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

The teams used the Researched Abuse, Diversion and Addiction-Related Surveillance (RADARS) drug database to establish the prevalence of diversion. The system collects information from 300 law enforcement jurisdictions in the United States on sources of diversion such as undercover street purchases, arrests for distribution, and hospital and pharmacy theft.

It quickly became clear that street markets had developed for antiretroviral medications.

The RADARS data showed that 1518 cases of diversion had been investigated in 7 geographically diverse jurisdictions over 39 calendar quarters.

Dr. Kurtz and his team used this information to develop a survey about medical care, treatment, and adherence and diversion. It was completed by 515 men.

Of the 46.4% of respondents who were infected with HIV, 91.6% were receiving medical care. Nearly 80% of these men were prescribed much-needed antiretrovirals, yet 27.5% reported selling or trading their medications at some point, and 19.0% reported doing so in the previous year.

The respondents reported diverting their medications to share or trade with friends, to acquire money or illicit drugs, or to get rid of unused medications. Not surprisingly, antiretroviral diverters were more likely to be dependent on substances than nondiverters (74.5% vs 58.7%; P = .046), and more diverters reported recently trading sex for money or drugs (60.8% vs 32.6%).

Who is buying these drugs?

The demand for antiretrovirals increased with their recent approval for pre-exposure prophylaxis.

Party Packs Called MTV

"We've known from the literature and anecdotally that tenofovir, specifically, has been used for pre-exposure prophylaxis since at least 2009," Dr. Kurtz explained. It was even being distributed in clubs in Miami and other cities as a party pack called MTV, which consists of methamphetamine, emtricitabine plus tenofovir (Truvada), and sildenafil (Viagra). "That was a strong signal about what was going on."

"Frankly, we don't know who the purchasers are. Pill brokers are likely a big part of it, going in the back door of pharmacies, and recirculation. We need studies now to look at the demand side," he said.

"There's been a big black market in South Florida for many years," said Michael Weinstein, president of the AIDS Healthcare Foundation. "First off, Miami is the capital of Latin America. If the drugs are not available back home, you go to Miami. However, that's changed over time as treatment has become more common in poorer countries, so the incentive is now somewhat less."

Another market is individuals who are undocumented, explained Weinstein. "Usually, if you need to reduce the expense of your medications, you go to a government-sponsored clinic, but that requires providing some kind of information about yourself. Even though places like the Ryan White Program do cover undocumented patients, there are many who fear engagement with a government-run or any other type of formal facility."

Weinstein said that Gilead, the maker of Truvada, is somewhat complicit in the creation of the black market by aggressively promoting a product that, he believes, should not have been approved as a preventive measure in the first place.

"The whole premise of pre-exposure prophylaxis is dangerous and unwarranted based on study results. In the real world, pre-exposure prophylaxis relies on adherence, which in my opinion cannot be accomplished. People who already have the virus are often noncompliant. What you're going to wind up with is more infections and more resistance."

Dr. Kurtz and Mr. Weinstein have disclosed no relevant financial relationships.

The 7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract MOPE133. Presented July 1, 2013.

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Quest Diagnostics Partners with CDC to Improve Hepatitis C Public Health Research to Promote Early Detection and Medical Intervention

Collaboration aims to improve health outcomes for the estimated 3.2 million Americans infected with hepatitis C

Jul 10, 2013

MADISON, N.J., July 10, 2013 /PRNewswire/ -- Quest Diagnostics (NYSE: DGX), the world's leading provider of diagnostic information services, today announced a collaboration with the U.S. Centers for Disease Control and Prevention (CDC) to improve public health analysis of hepatitis C screening, diagnosis and treatment, based on analysis of the company's national hepatitis C virus diagnostic information.

The collaboration aims to enhance screening, diagnosis and medical intervention for the approximately 3.2 million Americans infected with hepatitis C, promoting favorable health outcomes. The organizations will primarily focus on individuals born during 1945 through 1965. Individuals in this "baby boomer" generation are five times more likely than other adults to be infected, and one-time testing, as recommended by the CDC in 2012, could prevent more than 120,000 deaths in this age group.

In June 2013, the U.S. Preventive Services Task Force recommended one-time hepatitis C screening for all adults born between 1945 and 1965.

"Deaths from hepatitis C infection have nearly doubled over the past decade to now more than 15,000 a year.  Early detection and treatment of hepatitis C saves lives, but most people who are infected don't know it or are not being effectively treated," said Jay Wohlgemuth, M.D., senior vice president, science and innovation, Quest Diagnostics. "Our collaboration with the CDC underscores the importance of using diagnostic information to derive useful insights enabling effective prevention, detection and management programs for diseases with a significant impact on public health."

Under an agreement, medical experts, scientists and health informatics experts from Quest Diagnostics and the CDC's Division of Viral Hepatitis will share access to de-identified hepatitis C test results, in a HIPAA compliant manner, from the Quest Diagnostics Health Trends™ national clinical laboratory database, which represents every state and the District of Columbia. The de-identified data, with names and personally identifying information removed, will include results of screening and confirmatory diagnostic tests as well as genotyping and viral load tests used by clinicians to manage treatment. 

Data will be evaluated to identify and track epidemiological trends in hepatitis C virus infection, testing and treatment, and evaluate how those trends differ based on gender, age, geography and clinical management.  The organizations may jointly publish results of their research, such as in peer reviewed publications and scientific conferences.

"With 3 million Americans living with hepatitis C and up to 3 out of 4 who don't know they are infected, increased testing is critical to ensure that those who are infected receive life-saving care and treatment," said John W. Ward, M.D., director of CDC's Division of Viral Hepatitis. "Because these individuals are at serious risk for liver cancer, disease and death, I am excited about this innovative collaboration with Quest Diagnostics and believe it will help improve our understanding of how people access hepatitis C testing and care across the nation."

"This collaboration is an important step forward to producing actionable insights to aid public and clinical disease detection and management of hepatitis C," said Rick Pesano, M.D., Ph.D., medical director, infectious diseases. "Working with the CDC, Quest Diagnostics will lead the way for other providers to improve diagnosis and management of this disease, which in turn will help more people lead healthier lives."

Hepatitis C virus infection is the most common chronic bloodborne infection in the United States. The disease can cause liver damage and cancer and is a leading cause of liver transplants. Hepatitis C often does not manifest symptoms for decades. Early diagnosis, through laboratory blood tests, and treatment can help prevent liver damage, cirrhosis, liver cancer and death.

Quest Diagnostics provides comprehensive diagnostic information services for hepatitis C, including genotyping, risk stratifying and viral load testing, to aid the diagnosis, treatment, and monitoring of hepatitis C virus infection and disease.

About Quest Diagnostics Health Trends™ Reports
Quest Diagnostics Health Trends™ Reports provide insights into critical health issues, based on diagnostics data, affecting large numbers of Americans. The reports identify trends in disease and wellness based on analysis of de-identified test data from Quest Diagnostics, which maintains the largest private clinical laboratory database in the United States. Quest Diagnostics Health Trends™ Reports are published in peer-reviewed medical journals, at medical conferences and by the company as a public service. Previous reports have focused on prescription medication misuse, allergies and asthma, cardiovascular disease, chronic kidney disease, diabetes, heart disease, influenza, pregnancy, rotavirus, sexually transmitted infections and wellness. Visit QuestDiagnostics.com/HealthTrends.

About Quest Diagnostics
Quest Diagnostics is the world's leading provider of diagnostic information services that patients and doctors need to make better healthcare decisions. The company offers the broadest access to diagnostic information services through its network of laboratories and patient service centers, and provides interpretive consultation through its extensive medical and scientific staff. Quest Diagnostics is a pioneer in developing innovative diagnostic tests and advanced healthcare information technology solutions that help improve patient care. Additional company information is available at QuestDiagnostics.com. Follow us at Facebook.com/QuestDiagnostics and Twitter.com/QuestDX.

Quest, Quest Diagnostics, and all associated Quest Diagnostics registered or unregistered trademarks are the property of Quest Diagnostics. All third-party marks are the property of their respective owners. 

Quest Diagnostics Contacts:
Wendy Bost (Media): 973-520-2800
Dan Haemmerle (Investors): 973-520-2900

SOURCE Quest Diagnostics Incorporated

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Randomized Controlled Trial of Danoprevir Plus Peginterferon Alfa-2a and Ribavirin in Treatment-Naive Patients with HCV Genotype 1 Infection

Gastroenterology

Article in Press

P. Marcellin, C. Cooper, L. Balart, D. Larrey, T. Box. E. Yoshida, E. Lawitz, P. Buggisch, P. Ferenci, M. Weltman, E. Labriola,Tompkins, S. Le, Pogam, I. Nájera, D. Thomas, G. Hoope,N.S. Shulman, Y. Zhang, M.T. Navarro, C.Y. Lim, M. Brunda, N.A. Terrault, E.S. Yetzer

Received 3 January 2013; received in revised form 20 June 2013; accepted 20 June 2013. published online 28 June 2013.

Accepted Manuscript

Abstract

Background

& Aims: The combination of an HCV protease inhibitor, peginterferon, and ribavirin is the standard of care for patients with HCV genotype 1 infection. We report the efficacy and safety of response-guided therapy with danoprevir (a potent second-generation protease inhibitor), peginterferon alfa-2a (40 KD), and ribavirin in these patients.

Methods

Treatment-naive patients (n=237) were randomly assigned to groups given 12 wks of danoprevir (300 mg every 8 h; 600 mg every 12 h, and 900 mg every 12 h) or placebo plus peginterferon alfa-2a and ribavirin, followed by peginterferon alfa-2a and ribavirin. Patients given danoprevir who had an extended rapid virologic response (eRVR_4–20: HCV RNA <15 IU/mL during wks 4–20) stopped therapy at wk 24; those without an eRVR_4–20 continued therapy to 48 wks. Patients who were given placebo received 48 wks of peginterferon alfa-2a and ribavirin. The primary efficacy endpoint was sustained virologic response (SVR: HCV RNA <15 IU/mL after 24 wks without treatment).

Results

Rates of SVR were higher among patients given danoprevir 300 mg (68%), 600 mg (85%), and 900 mg (76%) than placebo (42%) (95% confidence interval [CI], 26%–59%). Seventy-nine percent of patients given danoprevir 600 mg had an eRVR_4–20; among these, 96% had an SVR. Serious adverse events were reported in 7%–8% of patients given danoprevir and 19% given placebo. Four patients given danoprevir (1 patient in the 600 mg group and 3 in the 900 mg group) had reversible, grade 4 increases in alanine aminotransferase (ALT); this led to early discontinuation of the 900 mg arm of the study.

Conclusions

The combination of danoprevir, peginterferon alfa-2a, and ribavirin leads to high rates of SVR in patients with HCV genotype 1 infection, but high doses of danoprevir can lead to grade 4 increases in ALT. Studies of lower doses of danoprevir with ritonavir, to reduce overall danoprevir exposure while maintaining potent antiviral activity, are underway. Clinicaltrials.gov number, NCT00963885.

Keywords: danoprevir (RG7227), hepatitis C virus, sustained virologic response, response-guided therapy

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Marijuana not associated with liver disease progression in HIV/HCV coinfection

Provided by Healio

Brunet L. Clin Infect Dis. 2013;doi:10.1093/cid/cit378.

July 10, 2013

Smoking marijuana did not lead to liver disease progression among people coinfected with HIV and hepatitis C, researchers from McGill University have found.

“The literature regarding the effects of cannabis on liver diseases is conflicting,” the researchers wrote in Clinical Infectious Diseases. “Cell culture and animal model studies support that cannabinoids could have a therapeutic effect on liver injury and fibrosis progression. However, three cross-sectional studies in patients with chronic HCV suggest that daily cannabis use is associated with fibrosis and steatosis.”

The study included 690 patients who were positive for HCV but did not have significant fibrosis or end-stage liver disease (ESLD). The patients were part of the Canadian Coinfection Cohort and visited their providers every 6 months, contributing to 1,875.3 person-years of follow-up, with a median follow-up time of 2.7 years. At each visit, they reported their marijuana use, including how often they smoked and the amount they consumed.

At baseline, 53% of the patients reported smoking marijuana in the past 6 months. The median consumption was seven joints per week, and 40% of the patients smoked daily. Among the patients, 19.1% developed liver fibrosis and 14.8% developed cirrhosis, according to APRI score. Eleven patients developed ESLD and eight patients developed clinical cirrhosis.

Multivariate analysis showed that marijuana use was not associated with fibrosis or cirrhosis as measured by APRI score. Smoking marijuana did accelerate progression to clinical cirrhosis (HR=1.33 per 10 joints/week; 95% CI, 1.09-1.62). Marijuana smoking was also associated with an increased risk of clinical cirrhosis and ESLD combined (HR=1.13; 95% CI, 1.01-1.28). However, if the exposure lagged 6 to 12 months before diagnosis, they were no longer associated (HR=1.10; 95% CI, .95-1.26).

“A causal association is unlikely: hazard ratios were weak and most importantly were attenuated when accounting for temporality in the exposure-disease relationship and there was no dose-response relationship,” the researchers wrote. “It is likely that previous studies have been biased by reverse causality as patients use more marijuana to relieve symptoms as liver disease progresses.”

Disclosure: The researchers report no relevant financial disclosures.

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Around 10m suffering from hepatitis in Pakistan: experts

Obaid Abrar Khan
Tuesday, July 09, 2013
From Print Edition

Rawalpindi: A table talk on ‘Importance of hepatitis awareness, prevention and treatment’ was organised by the Mir Khalil-ur-Rehman Memorial Society (MKRMS) with the collaboration of Roche Pharma here on Monday.

Minister of State for National Health Services, Regulations and Coordination Saira Afzal Tarar was the chief guest on the occasion. Khyber-Pakhtunkhwa Minister for Health Shoukat Ali Yousafzai attended the talk as guest of honour. Professor of Medicine at Rawalpindi Medical College Professor Dr. Shoaib Shafi and Professor Dr. Muzzaffar Lateef Gill attended the event as keynote speakers. Senior Editor and Mir Khalil-ur-Rehman Memorial Society Chairman Wasif Nagi was the host.

The participants of the talk said that around 10 million citizens of Pakistan were suffering from hepatitis. A large number of residents of Hafizabad and Mandi Bahauddin were suffering from this silent killer.

Minister of State for National Health Services, Regulations and Coordination Saira Afzal Tarar, in her address, said that the federal government has been working on the National Health Policy. She said that a meeting would be called in this regard by the end of this month. “We have constituted a task force on national level to make the National Health Policy,” she added.

She said that after taking charge she found corruption and mismanagement in all departments. She said that the list of corrupt and non-professional officials has been sent to Prime Minister’s Office. “I am searching for eligible candidates for key posts to make the health department active and effective,” she added.

Talking about hepatitis, Saira Afzal Tarar said that there was a need to spread awareness among the public about preventive measures and to fight against this silent killer. She said that it was the responsibility of qualified doctors to come forward and give suggestions to the government and fight against hepatitis.

Shoukat Ali Yousafzai said that around 480,000 patients were suffering from Hepatitis-B and around 1,680,000 were suffering from Hepatitis-C in Khyber-Pakhtunkhwa. “A survey has found that most patients of hepatitis are from Peshawar,” he added.

He said that the Khyber-Pakhtunkhwa government has been giving special attention to health and they have distributed equipment in all districts for free testing of hepatitis. He said that there was a need to create awareness among the public and to tell them to keep the environment clean and protect themselves from this silent killer.

Dr. Shoaib Shafi said: “We are fighting against terrorism. We have to fight against hepatitis which is more dangerous.” He said that around 10 million citizens of Pakistan were suffering from hepatitis. Most of the hepatitis patients were from Hafizabad and Mandi Bahauddin. As many as 8.3% of patients were from Rawalpindi Division and 13.5% of women were suffering from this disease, which was alarming situation for the government. “Around 1,100 patients are under treatment at the Liver Centre of Benazir Bhutto Hospital, Rawalpindi,” he added.

Talking about problems in treatment, Dr. Shoaib Shafi said that there was no facility for hepatitis test in government hospitals, whereas in private laboratories this test was expensive and out of the reach of poor people. The government should make arrangements to give this facility in government hospitals free of cost and it also set up liver transplant centres in public hospitals.

About the symptoms of hepatitis, Dr. Shoaib Shafi said that most patients were diagnosed at the last stage of the disease because of lack of awareness. “This disease spreads due to filthy water, used syringes and infected blood transfusion,” he said.

Professor Dr. Muzaffar Lateef Gill (Sitara-i-Imtiaz) said: “Unfortunately, we are not giving quality treatment to patients of hepatitis in government hospitals. We have made two standards of treatment — one is for the poor, which is not quality treatment, and the other one is for wealthy people, which is very effective.”

He said that although government was providing free treatment of hepatitis in government hospitals but the efficacy of injections used was not so good. “These injections treat only 60% of patients and 25% patients get the virus back.” “The government should give quality treatment at low cost,” he said and added that doctors should also play their role and think before giving medicines to the patients of hepatitis.

Dr. Muzaffar Lateef Gill said that different pharmaceutical companies were also taking advantage and marketing low quality injections from different countries. The government should take notice of such medicines, which are banned all over the world but still available in Pakistan, he concluded.

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Review of direct-acting antiviral agents for the treatment of chronic hepatitis C

Expert Opin Investig Drugs.

Review

Posted online on June 4, 2013. (doi:10.1517/13543784.2013.806482)

Nihar Shah ^†1 MD Fellow in Hepatology, Tracey Pierce ² BA Clinical Research Coordinator & Kris V Kowdley ³ MD FACP Director

¹ Digestive Disease Institute, Virginia Mason Medical Center,

1100 Ninth Ave, Mail-stop: C3 GAS, Level 1, Buck Pavilion, Seattle, WA 98101

, USA +1 206 223 2319; +1 206 341 1188; kris.kowdley@vmmc.org

² Digestive Disease Institute, Virginia Mason Medical Center,

1100 Ninth Ave, Mail-stop: C3 GAS, Level 1, Buck Pavilion, Seattle, WA 98101

, USA

³ Digestive Disease Institute, Virginia Mason Medical Center, Liver Center of Excellence,

1100 Ninth Ave, Mail-stop: C3 GAS, Level 1, Buck Pavilion, Seattle, WA 98101

, USA

^†Author for correspondence

Introduction: Rapid breakthroughs in the treatment of hepatitis C virus (HCV) infection have dramatically altered the treatment landscape for this chronic disease. In 2011, the protease inhibitors (PIs) boceprevir and telaprevir in combination with peginterferon (peg-IFN) and ribavirin (RBV) were the first direct-acting antivirals (DAAs) approved in the United States for treatment of genotype (GT) 1 HCV. Several DAAs currently in late-stage clinical trials, including NS3/NS4A serine PIs, NS5A inhibitors, NS5B polymerase inhibitors (both nucleoside and non-nucleoside) and cyclophilin inhibitors, both with and without peg-IFN and RBV, are promising for the treatment of HCV. DAA regimens offer several advantages including that they specifically target HCV viral replication and thus appear to be less dependent on host characteristics, very high SVR rates accompanied by fewer side effects (SE) and lower pill burdens. A review on the treatment of HCV is important and timely as the development on DAAs is progressing rapidly and the health-care providers need to be aware about this as these regimens are anticipated to become clinically available soon.

Areas covered: The literature was searched and reviewed using PubMed as well as data gathered from those presented at the international liver meetings, AASLD and EASL as well as CROI.

Expert opinion: With the potential of eliminating IFN and RBV, several DAAs under clinical development appear to be promising using novel approaches with good antiviral effects, shorter duration and lower SE profile.

Keywords

ABT-267, ABT-333, ABT-450, asunaprevir, boceprevir, cirrhosis, cyclophilin inhibitors, daclatasvir, danoprevir, directly acting antiviral agents, faldaprevir, hepatitis C virus, ledipasvir, mericitabine, NS5A inhibitors, NS5B polymerase inhibitors, null responders, partial responders, pegylated interferon, protease inhibitors, relapsers, resistance, ribavirin, simeprevir, sofosbuvir, SVR, telaprevir, treatment naïve

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Poorer Health for Acetaminophen Overdose Survivors than Other Liver Failure Patients

Journal Liver Transplantation

Press Release

July 09, 2013

Spontaneous survivors of acetaminophen overdose have significantly lower overall health compared to survivors or transplant recipients following acute liver failure caused by non-drug induced liver injury according to a new study published online in Liver Transplantation, a journal of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society. Findings show that acetaminophen overdose survivors report more days of impaired mental and physical health, and activity limitations due to poor health, pain, anxiety and depression.

Patients are diagnosed with acute liver failure (ALF) when severe liver dysfunction occurs, along with blood clotting or bleeding disorders (coagulopathy) and compromised brain function (encephalopathy). Studies report that up to 3,000 patients develop ALF in the U.S. each year and 67% of these patients will survive, but nearly 30% of these patients require emergency liver transplantation. However, long-term consequences of ALF and health-related quality of life (HRQOL) of survivors, remains unclear.

To expand understanding of the quality of life and function of adult ALF survivors, a team led by Dr. Robert Fontana from the University of Michigan Medical Center in Ann Arbor conducted a prospective observational study. Patients diagnosed with ALF between January 1998 and July 2010 were included in the study. Participants agreed to follow-up at one and two years following ALF.

Results show that of the 282 ALF patients—125 liver transplantation recipients (10.7% due to acetaminophen overdose) and 157 spontaneous survivors of which 95 were acetaminophen overdose patients and 62 were survivors of non-drug induced liver failure. Patients that survived acetaminophen overdose reported significantly lower general health scores. Acetaminophen overdose survivors had higher rates of substance abuse and psychiatric disease compared to non-acetaminophen overdose survivors and transplant recipients. Participants who were survivors of non-intentional acetaminophen overdose were less likely to have psychiatric comorbidity compared to patients who intentionally overdosed at 48% and 82%, respectively.

The combined group of spontaneous survivors of ALF reported “fair/poor” health and more than 14 days of physical or mental health impairment compared to the general population in the U.S. This group also had more limitation in functional activity due to poor health. “Our findings indicate that adult survivors of ALF have reduced quality of life compared to those of similar age and gender in the general population,” concludes Dr. Fontana. “Additional investigations of brain function by our team are underway to further understanding of the type and severity of cognitive impairment reported by ALF survivors.”

This current study was funded in part by a grant from the National Institute of Diabetes, Digestive and Kidney Diseases (DK U-01-58369) to the United States Acute Liver Failure Study Group (ALFSG), which is led by Dr. William Lee, Professor of Internal Medicine at UT Southwestern Medical Center in Dallas. ALFSG is a National Institutes of Health-funded consortium of investigators in the United States focused on studying acute liver failure.

View the abstract for this article on Wiley Online Library

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Liver stiffness more predictive of decompensation than biopsy results in HIV/HCV coinfection

Provided by Healio

July 9, 2013

Liver stiffness measurement is similarly predictive of overall mortality and more predictive of decompensation than liver biopsy results among patients with HIV/HCV coinfection, according to data presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.

Researchers evaluated 297 patients coinfected with HCV and HIV who underwent liver biopsy (LB) and liver stiffness measurement (LSM) within 12 months of one another. The midway point between the procedures was considered the baseline date for analysis. Ninety-three percent of participants were receiving therapy with antiretrovirals at baseline, with undetectable plasma HIV RNA levels in 79% of cases and a median CD4 cell count of 514 cells/mcL.

Among evaluable participants after 26 cases were lost to follow-up, overall mortality across the cohort was 1.56 deaths per 100 person-years. Increased risk for death was associated with elevated LSM values (adjusted HR=1.28; 95% CI, 1.12-1.46 per 5 kPa increase) and fibrosis stage at baseline as indicated by LB (aHR=1.56; 95% CI, 1.02-2.4). Liver decompensation occurred at a rate of 1.59 cases per 100 person-years, with LSM (aHR=1.37; 95% CI, 1.21-1.54) and fibrosis stage at baseline (aHR=1.67; 95% CI, 1.15-2.43) as predictive factors.

Integrated discrimination improvement (IDI) analysis indicated that models incorporating LMS values performed 3.9% better in predicting mortality than models incorporating LB, but was not statistically significant (P=.072). For the prediction of liver decompensation, LMS-based models performed 8.4% better than LB-based models (P=.045).

“LSM-based prediction achieves a similar yield [to] LB-based models to predict overall mortality in HIV/HCV coinfected patients, and the former could better predict liver decompensations,” the researchers concluded. “LSM may replace LB as [a] prognostic tool in this setting.”

For more information:

Macías J. TUAB0104: Prediction of Survival and Decompensations of Cirrhosis Among HIV/HCV Coinfected Patients: A Comparison of Liver Stiffness Versus Liver Biopsy. Presented at: IAS Conference on HIV Pathogenesis, Treatment and Prevention; June 30-July 03, 2013; Kuala Lumpur, Malaysia.

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Poorer antiretroviral response among HIV patients with HBV, HCV coinfection

Provided by Healio

July 9, 2013

Patients with HIV coinfected with hepatitis B or hepatitis C virus experienced poorer outcomes from antiretroviral therapy compared with monoinfected patients in a study presented at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention in Kuala Lumpur, Malaysia.

Researchers evaluated data collected from the TREAT Asia HIV Observational Database on 7,455 patients with HIV treated at 22 Asian hospitals. All participants received antiretroviral therapy (ART), with a target HIV viral load (VL) of fewer than 1,000 copies/mL. Among patients with evaluable test results, 10.45% were coinfected with HBV and 15.2% with HCV.

After 180 days of therapy, CD4 counts were significantly lower among patients coinfected with either HBV (adjusted difference=–15.5 cells/mcL; P=.011) or HCV (aDiff=–37.8 cells/mcL; P<.001) compared with monoinfected patients after initiating ART. CD4 increases were smaller among those with HIV subtype CRF01AE compared with subtype B (–35.5 cells/mcL; P=.026).

The target VL was achieved in a median of 1.28 years within the cohort. Patients coinfected with HBV or HCV experienced a longer time to VL than monoinfected participants, but this difference was not statistically significant.

Coinfected patients had poorer survival than monoinfected patients. Multivariate analysis indicated a significant association between mortality and HCV coinfection (adjusted HR=1.81; 95% CI, 1.2-2.71). No association was observed between HIV VL and coinfection with either HBV or HCV.

“In this Asia regional HIV cohort, patients with HBV or HCV coinfection had significantly lower CD4 counts [and] smaller CD4 increases after 180 days of ART,” the researchers concluded. “We need to test, identify and initiate [highly active] ART early in HBV and HCV coinfected [patients] to have a better treatment effect.”

For more information:

Chen YMA. TULBPE13: HBV and HCV Coinfection: Long-term Immunological, Virological and Survival Outcomes Following cART. Presented at: IAS Conference on HIV Pathogenesis, Treatment and Prevention; June 30-July 03, 2013; Kuala Lumpur, Malaysia.

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Ancient Dinosaur Birds Were Infected With Hepatitis B

Zebra Finches are one of the birds that hold a trace of ancient hepatitis B in their genes. Photo: FurLined

July 9, 2013 1:06 pm

Want to know something sad about the great-great-great-great-…great-great-great grandparent of all modern finches, weavers, crows, jays, robins and all songbirds? She was carrying around the genes of hepatitis B. The virus that today kills around 620,000 people each year worldwide, it turns out, is old. Really old. A recent study analyzing the history of hepatitis B found that the virus was going around infecting birds at least 82 million years ago.

That ancient bird was the precursor to all modern passerines and neoavian birds and lived during the Late Mesozoic, “back when the dinosaurs were still very much alive,” says the pseudonymous blogger GrrlScientist.

Some time around 82 million years ago, says Science News, “a hepatitis B virus infected an ancient bird and got stuck in its genome.” Normally viruses evolve really quickly. But, once its genes got stuck in the genome of the ancient bird, says GrrlScientist, the rate of change for the virus’ genes “slows to the same pace as that of the host’s DNA,” meaning that scientists looking at modern birds’ genes can see what amounts to a fossilized record of the ancient hepatitis B virus. Science News:

The reconstructed Mesozoic-era virus is remarkably similar to the hepatitis B virus that infects people today, the team found.“We’ve had 82 million years of evolution, but they have the same proteins,” says Suh, who now works at Uppsala University in Sweden.

One exception is a notorious protein called X protein. The protein has been implicated in causing liver cancer and is necessary for the virus to replicate in humans. Since X protein is missing from the hepatitis B viruses that infect modern-day birds, many scientists thought that bird viruses had lost the protein during evolution. But the ancient virus doesn’t contain X protein either, which means that the bird version probably never had it, and X marked mammalian hepatitis B viruses only recently.

So, the researchers think that birds got hepatitis B first, and then it later learned to live in mammals. In the study, the scientists say that learning about the virus’ long history can help us understand how it evolved. They also say that it could help with the “in-vitro resurrection of Mesozoic hepadnaviruses.” But maybe we can skip that part.

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Boceprevir an option for patients with HIV and HCV

By: DOUG BRUNK, Ob.Gyn. News Digital Network

07/09/13

FROM THE LANCET INFECTIOUS DISEASES

Among adults infected with both HIV and hepatitis C virus, the addition of boceprevir to a combination of peginterferon and ribavirin significantly increased the rate of sustained virological response compared with those who received placebo, results from a 44-week, multicenter phase II study demonstrated.

"Rates of SVR at follow-up week 24 were increased with boceprevir in all subgroups of patients, irrespective of demographic or baseline characteristics," researchers led by Dr. Mark S. Sulkowski of Johns Hopkins University, Baltimore, reported in the July issue of the Lancet Infectious Diseases. Although SVR after treatment with peginterferon and ribavirin has been associated with improved survival, "this regimen has been relatively ineffective (SVR, 25%-30%) in patients with HIV and HCV genotype 1 infection," they wrote.

"Addition of an HCV protease inhibitor (boceprevir or telaprevir) to peginterferon-ribavirin has emerged as the standard of care for the treatment of HCV genotype 1 infection alone. Use of HCV protease inhibitors in patients infected with HIV and HCV has been restricted by the dearth of available safety and efficacy data."

For the study, which was conducted between Jan. 15 and Dec. 29, 2010, at 30 academic and nonacademic study sites, 99 adults with untreated HCV type 1 genotype infection and controlled HIV were randomized in 1:2 fashion to receive peginterferon 1.5 mcg/kg per week with weight-based ribavirin (600-1,400 mg/day) for 4 weeks, followed by peginterferon-ribavirin plus either placebo (control group) or 800 mg of boceprevir three times daily (boceprevir group) for 44 weeks (Lancet Infect. Dis. 2013;13:597-605).

The primary endpoint of interest was sustained virological response (defined as undetectable plasma HCV RNA) at follow-up week 24 after the end of treatment.

Of the 99 patients, 98 received at least one treatment dose. Of these, 64 were in the boceprevir group and 34 were in the control group. The researchers reported that at follow-up week 24, 63% of patients in the boceprevir group achieved SVR, compared with 29% of controls, a difference of 33.1% that reached significance (P = .0008). Compared with controls, a higher proportion of the boceprevir group experienced adverse events, including anemia (41% vs. 26%, respectively), pyrexia (36% vs. 21%), decreased appetite (34% vs. 18%), dysgeusia (28% vs. 15%), vomiting (28% vs. 15%), and neutropenia (19% vs. 6%). In addition, 4 patients in the control group and 3 in the boceprevir group had HIV viral breakthrough, defined as two consecutive HIV RNA values of at least 50 copies/mL.

"Boceprevir did not seem to add significant risk when used in combination with peginterferon-ribavirin therapy, and no new adverse events were reported," the researchers wrote. "HIV control was well maintained in patients taking boceprevir and HIV protease inhibitors. Drug interactions between boceprevir and HIV protease inhibitors did not have a clinically significant effect on HCV response or HIV control in this study. In view of the hepatic and extrahepatic benefits associated with SVR at follow-up week 24 in patients infected with HIV and HCV, boceprevir in combination with peginterferon-ribavirin might be an important therapeutic option for patients with such coinfection."

Merck markets boceprevir under the brand name Victrelis. Merck sponsored and funded the study. Dr. Sulkowski and numerous other coauthors disclosed having received consulting fees and research grants from the company.

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Sorrento Therapeutics and Ben-Gurion University Sign an Agreement for the Development of Anti-Hepatitis C Virus Antibodies

PRESS RELEASE

July 9, 2013, 9:00 a.m. EDT

SAN DIEGO and BEER-SHEVA, Israel, July 9, 2013 /PRNewswire via COMTEX/ -- Sorrento Therapeutics, Inc. (otcqb:SRNE)(otcqb:Sorrento) and B.G. NEGEV TECHNOLOGIES AND APPLICATIONS LTD. announced today that they have entered into an option and license agreement covering several fully human anti-Hepatitis C Virus (HCV) antibody clones identified, in the laboratory of Dr. Leslie Lobel, M.D., Ph.D., from patients who have recovered from HCV infections. Sorrento plans to develop these early findings into a potential therapeutic product. This collaborative effort utilizes the respective strengths of each organization to create an important product opportunity consisting of therapeutic and/or prophylactic agents against HCV infections. Sorrento will be responsible for developing the perspective anti-HCV antibody products.

"Sorrento has already achieved many successes using its proprietary G-MAB� library to identify, characterize and develop fully human antibodies against difficult targets relevant to infectious agents. We are excited to be working with Dr. Lobel to add a program targeting HCV to our existing portfolio of therapeutic antibodies for the prevention and/or treatment of major infectious diseases", said Henry Ji, Ph.D., President and CEO of Sorrento.

"We are pleased to be collaborating with Sorrento to develop our fully human anti-HCV antibody clones into potential anti-HCV therapeutics", said Leslie Lobel, M.D., Ph.D., Professor and Vice Chair of the Department of Microbiology, Immunology and Genetics at the Ben Gurion University of the Negev.

About Hepatitis C Virus Infections

According to the Centers for Disease Control (CDC), more than 170 million people worldwide are chronically infected with HCV, including approximately 3.2 million people in the United States. The combined incidence and prevalence of HCV infection is estimated to reach over 13 million people in the United States, EU, and Japan alone, of which only 13% are estimated to be diagnosed and treated.[1] In 2009, the total annual medical costs in the United States for people with hepatitis C are estimated to reach over $30 billion. In the next 20 years, total annual medical costs are expected to increase to approximately $85 billion.[2]

HCV is spread through direct contact with contaminated blood and ultimately leads to serious liver diseases, including liver damage, cirrhosis, liver failure or liver cancer which are all long term consequences of untreated chronic HCV infection.[3] Hepatitis C is the leading cause of liver transplantations in the United States and is reported to contribute to 15,000 deaths annually.[4],[5] With proper treatment, chronic hepatitis C can be cured; however, patients remain at an increased risk for progressive liver disease if they have not achieved complete viral clearance.[6],[7]

About Sorrento Therapeutics, Inc.

Sorrento Therapeutics, Inc. is a publicly-traded, development-stage biopharmaceutical company engaged in the discovery, acquisition, development and commercialization of proprietary drug therapeutics for addressing significant unmet medical needs in the Unites States, Europe and additional international markets. Sorrento Therapeutics' primary therapeutic focus is oncology but it is also developing therapeutics products for other indications, including inflammation, metabolic, and infectious diseases. Sorrento Therapeutics' proprietary G-MAB� fully-human antibody library platform was designed to facilitate the rapid identification and isolation of highly specific antibody therapeutic product candidates that bind to disease targets appropriate for antibody therapy. More information is available at www.sorrentotherapeutics.com

About Ben-Gurion University of the Negev

Created in 1969 with the mandate to bring development to the region, BGU is internationally-recognized for its unique pioneering spirit that combines outstanding academics and research with a commitment to the community. With more than 20,000 students, five Faculties and a number of internationally-acclaimed research institutes, the University has become a world leader in interdisciplinary research in cutting-edge fields that range from desert studies to nano- and biotechnology, Hebrew literature to international medicine.

About B.G. NEGEV TECHNOLOGIES AND APPLICATIONS LTD

BGN Technologies is the technology transfer company of Ben-Gurion University of the Negev, responsible for the commercialization of know-how and inventions of the University's researchers. Through the development of novel technologies and creative partnering with industry and investors, BGN brings value to the technological marketplace. BGN files worldwide patent applications and manages BGU's large patent portfolio.

Forward-Looking Statements

This press release contains forward-looking statements subject to risks and uncertainties that could cause actual results to differ materially from those projected. Words such as "assumes," "plans," "believes," "expects," "anticipates," and "will," and similar expressions, are intended to identify forward-looking statements. Forward-looking statements include statements about the clinical trial results from third parties, and the preclinical and clinical development of Sorrento's human antibody therapeutics. All such forward-looking statements are based on Sorrento's current beliefs and expectations, and should not be regarded as a representation by Sorrento that any of its plans will be achieved. Actual results may differ materially from those set forth in this press release due to the risks and uncertainties inherent in Sorrento's businesses; the scope and validity of patent protection for Sorrento's platform technologies, and the risk that the development or commercialization of product candidates may infringe the intellectual property rights of others; the potential that Sorrento may require substantial additional funding in order to obtain regulatory approval for and commercialize Sorrento's proprietary G-MAB� fully-human antibody library platform technologies or product candidates; and additional risks set forth in Sorrento's filings with the Securities and Exchange Commission. These forward-looking statements represent Sorrento's judgment as of the date of this release. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement and Sorrento undertakes no obligation to revise or update this press release to reflect events or circumstances after the date hereof. This caution is made under the safe harbor provisions of Section 21E of the Private Securities Litigation Reform Act of 1995.

[1] BioMedTracker, DataMonitor, 2013.[2] Pyenson B, Fitch K, and Iwasaki K. Consequences of Hepatitis C Virus (HCV): Costs of a Baby Boomer Epidemic of Liver Disease. Milliman, Inc. May 2009[3] Centers for Disease Control and Prevention. Hepatitis C Fact Sheet: CDC Viral Hepatitis. Available at: http://www.cdc.gov/hepatitis/HCV/PDFs/HepCGeneralFactSheet.pdf Updated June 2010.[4] Volk MI, Tocco R, Saini S, Lok, ASF. Public health impact of antiviral therapy for hepatitis C in the United States. Hepatology. 2009; 50(6):1750-1755.[5] Ly KN, et al. The Increasing Burden of Mortality From Viral Hepatitis in the United States Between 1999 and 2007. Ann Intern Med. 2012; 156:271-278.[6] Morgan TR, Ghany MG, Kim HY, Snow KK, Lindsay K, Lok AS. Outcome of sustained virological responders and non-responders in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) trial. Hepatology. 2008; 50(Suppl 4):357A (Abstract 115).[7] Veldt BJ, Heathcote J, Wedmeyer H. Sustained virologic response and clinical outcomes in patients with chronic hepatitis C and advanced fibrosis. Annals of Internal Medicine. 2007; 147: 677-684.

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SOURCE Sorrento Therapeutics, Inc.

Comparing East vs West in Hep C Patient Understanding

Provided by Eye for Pharma

Posted by Mary Assimakopoulos on Jul 8, 2013

In this month’s column we look at Hepatitis C and examine the differences (and similarities) between the causes of non-adherence in China and the US.

In this month’s column we look at Hepatitis C, an infectious disease spread mainly by blood-to-blood contact which affects the liver. We recently conducted research amongst Hep C sufferers in China and the USA. Although there are differences in the way patients from these countries feel about their disease and their experiences of having Hep C, they share commonalities in terms of the problems they encounter on their patient journey.

First of all, because Hep C often remains asymptomatic for many years, the virus can go undetected for a long time. We found that only 16% of US patients and just 4% of China patients seek direct help because they suspect they might have caught an infectious disease. Only a third of patients are aware that by participating in high-risk activities such as sexual activity and intravenous drug use they could be putting themselves at risk.  The majority of patients in both markets are diagnosed through routine blood tests or a blood test given for other reasons (for example, blood tests are required in China when getting married or joining the army). This means that many patients fail to present until they are at a more advanced stage in their illness. It also means that diagnosis can come as quite a shock.

Patients in the USA are concerned about passing the virus onto others and the long-term effect having Hep C will have on their health. Christopher, 50, from the US was diagnosed nearly 10 years ago. He openly admits he was a heavy drug user, and knows this was his route of infection. He says, “a few years after my diagnosis, I really started to see the signs of the hepatitis C. I didn’t realise how much it would affect me”. He is suffering adversely with his disease and has fatigue, pain associated with his liver and severe depression. When talking about this, he says, “I was depressed anyway, but I didn’t want to be this depressed. I can’t work anymore and sometimes I cannot do simple things in the day. I just want to go back to how I used to be, living a full life.”

“‘I feel other people discriminate against me […] I find it hard to communicate with other people’”

In China, patients are more concerned about people finding out about their illness and being treated differently. One patient we spoke to who had contracted Hep C from an infected syringe when donating blood, said that friends and colleagues were unwilling to come close to him or eat with him at work. He said“I feel other people discriminate against me … On the one side I can’t get close to others as I am afraid I’ll infect them and on the other side they are also afraid I will infect them... I find it hard to communicate with other people”.

Secondly, our research found that even when diagnosed, many patients are not necessarily being treated. There are two reasons for this. In the US, patients are being “warehoused” whilst they wait for new treatments to be made available. A new generation of protease-inhibitors (PIs) which come with fewer side effects are currently in the final phases of development. A range of interferon-free regimens are also being developed, which will be even less invasive. Many physicians are encouraging patients to wait for these new drugs to become available, if appropriate, before starting treatment. For example, George, 69, from the USA, is not currently being treated as his doctor has encouraged him to wait until new products are available to him. He says, “My doctor tells me to hold the fort as there is something for me in the pipeline.”

In China, these new drugs will not be launched for some time. Patients are not being treated because they feel their symptoms are currently “too mild”. Zhang-Wei, 30, from China, was diagnosed with HCV 12 years ago, after contracting it through drug use. He is quite content about not receiving treatment (a joint decision between him and the doctor) as he is pleased to be able to save his money. He says he would only change this attitude if his condition worsened. He says, “when my condition gets worse, I know I have to receive treatment. My doctor will discuss the treatment with me, and I know I will have to accept it in order to live.”

“Pharma companies with Hep C treatments have a number of opportunities to influence patient outcomes at key stages in the patient journey”

The decision not to start treatment is understandable. The treatment programme is very intensive and comes with many side effects, and we highlight this as the third roadblock to effective outcomes. The treatment programme lasts a long time and carries a high pill burden. Patients have to be prepared to experience chronic fatigue, muscle ache, depression and anxiety, insomnia and headaches. For patients in China, who may also be self-pay, treatment also carries a high cost burden. If a patient is not covered by private medical insurance, they may be unable to afford it. Unsurprisingly, many patients in our survey had not been able to comply with the programme at some stage, with one quarter of US patients and one third of patients in China stating that the side effects had been worse than they expected.

Pharma companies with Hep C treatments have a number of opportunities to influence patient outcomes at key stages in the patient journey. They can help to raise awareness about the disease so that people present earlier. Increased awareness could also help to break down misconceptions about Hep C and reduce the discrimination experienced by patients who have been diagnosed, particularly in China.  They can help physicians educate recently diagnosed patients about their illness and about the benefits of undergoing treatment. To influence earlier treatment they should be mindful that both the patient and the physician will make decisions about treatment, and both will need to be convinced of the benefit of doing so. Finally, pharma can help physicians set expectations about the treatment programme and ensure that patients have a support network in order to help them adhere over a long period. For patients in China, pharma has to convince the patient of both the benefits of treatment and of the effectiveness of the drug they are given in order to convince them to spend money on it. They may need to work with financiers in putting together a payment programme to help patients overcome affordability issues.

---

Contact Mary Assimakopoulos marya@researchpartnership.com for more information.

Living with Hep C is an online patient survey which was undertaken amongst 611 patients diagnosed with Hep C in the USA and China. In-depth follow-up interviews were conducted with a small sample of patients in both markets. The survey was carried out by the Research Partnership.

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Coffee Reduces Risk for Hepatocellular Carcinoma: An Updated Meta-Analysis

Clin Gastroenterol Hepatol. 2013 May 6. pii: S1542-3565(13)00609-5. doi: 10.1016/j.cgh.2013.04.039. [Epub ahead of print]

Bravi F, Bosetti C, Tavani A, Gallus S, La Vecchia C.

Department of Epidemiology, Istituto di Ricerche Farmacologiche "Mario Negri," Milan, Italy; Department of Clinical Sciences and Community Health, Università degli Studi di Milan, Milan, Italy.

Abstract

BACKGROUND & AIMS: Coffee consumption has been proposed to reduce risk for hepatocellular carcinoma (HCC). We performed a meta-analysis of articles published through 2012 to provide updated information on how coffee drinking affects risk for HCC.

METHODS: We performed a PubMed/MEDLINE search of the articles published from 1966 through September 2012 for original articles, in English, on case-control or cohort studies that associated coffee consumption with liver cancer or HCC. We calculated the summary relative risk (RR) for any, low, and high consumption of coffee vs no consumption. The cut-off point for low vs high consumption was set to 3 cups per day in 9 studies and 1 cup per day in 5 studies.

RESULTS: The summary RR for any coffee consumption vs no consumption was 0.60 from 16 studies, comprising a total of 3153 HCC cases (95% confidence interval [CI], 0.50-0.71); the RRs were 0.56 from 8 case-control studies (95% CI, 0.42-0.75) and 0.64 from 8 cohort studies (95% CI, 0.52-0.78). Compared with no coffee consumption, the summary RR was 0.72 (95% CI, 0.61-0.84) for low consumption and 0.44 (95% CI, 0.39-0.50) for high consumption. The summary RR was 0.80 (95% CI, 0.77-0.84) for an increment of 1 cup of coffee per day. The inverse relationship between coffee and HCC risk was consistent regardless of the subjects' sex, alcohol drinking, or history of hepatitis or liver disease.

CONCLUSIONS: Based on a meta-analysis of 16 studies, the RR for any coffee consumption vs no consumption is 0.60. The association might partly or largely exist because patients with liver and digestive diseases reduce their coffee intake. However, coffee has been shown to affect liver enzymes and development of cirrhosis, and therefore could protect against liver carcinogenesis.

Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID: 23660416 [PubMed - as supplied by publisher]

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