Thursday, August 3, 2017

Michigan - Increases in HCV linked to the growing opioid crisis

MDHHS issues Annual Viral Hepatitis Surveillance Report, urges vigilance in light of hepatitis A outbreak in Southeast Michigan and growing opioid crisis
Contact: Jennifer Eisner

LANSING, Mich. – The Michigan Department of Health and Human Services today issued its annual Viral Hepatitis Surveillance Report on hepatitis B and C, as local health officials and MDHHS continue to investigate an outbreak of hepatitis A cases in Southeast Michigan. As vaccines exist to protect against hepatitis A and B, and hepatitis C is linked to the growing opioid crisis, Michigan is urging residents to learn the facts, particularly steps residents should take to protect themselves.

The annual report shows that morbidity and mortality associated with viral hepatitis infections are on the rise. Viral hepatitis-related hospitalizations, liver cancer incidence, liver transplants, and viral hepatitis deaths have all increased over the last decade. These trends are largely driven by the impact of chronic HCV infection.

Hepatitis A Virus (HAV) is transmitted person-to-person through the ingestion of fecal matter containing the virus. HAV can spread through food or water if proper hand hygiene is not used by food handlers, and close contact such as household or sexual contacts. Importantly, HAV is a vaccine preventable disease and MDHHS encourages HAV vaccination of at-risk individuals, particularly in light of the recent HAV outbreak in Southeast Michigan. From August 2016 through August 1, 2017, there have been 223 reported cases in the city of Detroit, Macomb, Oakland, St. Clair, and Wayne counties.

Hepatitis B Virus (HBV) is a pathogen transmitted person-to-person via contaminated blood. In 2016, 1,284 new HBV diagnoses were reported in Michigan. As HBV is also vaccine preventable, incidence has declined in recent years largely due to increased HBV vaccination coverage. However, there remains a significant burden of HBV in developing countries and immigrant populations. Though they make up only 3 percent of the Michigan population, Asians represent nearly 20 percent of the new HBV diagnoses reported in 2016.

Hepatitis C Virus (HCV) is also a blood-borne pathogen, but there is no vaccine for HCV. In 2016, 11,883 new HCV infections were reported, making it one of the most common reportable diseases in Michigan. During the same year, 2,060 of those new HCV infections occurred in persons aged 18-29 years old, compared to just 78 diagnoses in this age group in 2001. The epidemic of HCV in the young adult population is linked to the growing opioid crisis. History of injecting drugs, the primary risk factor for HCV transmission, was reported by 84 percent of those new HCV diagnoses. Statewide increases in HCV were correlated with a rise in heroin overdose deaths and heroin substance abuse treatment admissions over this same time frame. Battling the opioid epidemic continues to be a major focus of Michigan’s Opioid Taskforce and Stop Overdose Campaign.

HCV treatments, which can cure over 90 percent of persons with HCV, are effective at reducing the risk of death from cirrhosis and liver cancer. Unfortunately, many patients have not been treated and there remains a significant proportion of undiagnosed HCV infection across the state.

Surveillance for viral hepatitis infections is important for identifying trends in rates of infection, characterizing at-risk groups, evaluating prevention programs, and identifying outbreaks.

For more information about viral hepatitis, visit or Additional viral hepatitis statistics can be found in MDHHS’s Annual Viral Hepatitis Surveillance Report.,5885,7-339-73970_71692_71696-427888--,00.html

Ethnic disparities in advanced liver disease survival in Hep C

Of Interest
Steatosis: An Independent Risk Factor for Fibrosis in Chronic HCV
A study recently published in Digestive Disease Science found that hypertension, older age, obesity, and HIV are risk factors and that steatosis is an independent risk factor for liver fibrosis in African-Americans with chronic hepatitis C.

Ethnic disparities in advanced liver disease survival in Hep C
Published ahead of print, the Alimentary Pharmacology & Therapeutics examines ethnic disparities in progression to advanced liver disease and overall survival in patients with chronic hepatitis C.

Chronic hepatitis C can lead to cirrhosis and hepatocellular carcinoma.

A sustained virological response is associated with improved outcomes, however, its impact on different ethnic groups is unknown.

Dr Nguyen and colleagues evaluated ethnic differences in the natural history of chronic hepatitis C and the impact of sustained virological response.

The researchers conducted a cohort study of 8039 consecutive adult CHC patients seen at 2 medical centres in California between 1997 and 2016.

Individual chart review confirmed chronic hepatitis C diagnosis.

Asian and Hispanic but not African American patients had significantly higher cirrhosis and HCC incidence than Caucasians.

The researchers found that Hispanic ethnicity was independently associated with increased cirrhosis, and HCC risk compared to Caucasian.

The team observed that Asian ethnicity had a significant association with cirrhosis, and HCC risk. In patients who achieved sustained virological response, Hispanic ethnicity was no longer independently associated with cirrhosis or HCC. Dr Nguyen's team concludes, "Asian ethnicity was independently associated with increased cirrhosis and HCC risk."

"Similar findings were observed with overall survival among the ethnicities by sustained virological response status.

Aliment Pharmacol Ther. 2017;112.
Ethnic disparities in progression to advanced liver disease and overall survival in patients with chronic hepatitis C: impact of a sustained virological response
A. K. Le, C. Zhao, J. K. Hoang, S. A. Tran, C. Y. Chang, M. Jin, N. H. Nguyen, L. A. Yasukawa, J. Q. Zhang, S. C. Weber, G. Garcia, M. H. Nguyen

First published: 2 August 2017
DOI: 10.1111/apt.14241

View Full Text Article 

In summary, our study found Hispanic and Asian patients to have a higher risk of developing cirrhosis and HCC compared to Caucasian patients. With successful achievement of SVR, these ethnic disparities no longer hold significance, and rates of disease progression in all groups were reduced. Our results underscore the importance of early diagnosis, linkage to care and anti-viral therapy for CHC patients of all ethnic backgrounds. Lastly, while SVR was effective in eliminating the racial disparities and reducing the incidence of cirrhosis and HCC for all ethnicities, there were still a number of patients found to develop cirrhosis and HCC following SVR. Thus, we advocate for continued regular follow-up and HCC surveillance for CHC patients with advanced fibrosis or cirrhosis even after successful SVR. Further research is needed to identify clinical and genetic factors predisposing patients to continued disease progression and HCC development despite SVR.

Chronic hepatitis C (CHC) can lead to cirrhosis and hepatocellular carcinoma (HCC). A sustained virological response (SVR) is associated with improved outcomes, however, its impact on different ethnic groups is unknown.

To evaluate ethnic differences in the natural history of CHC and the impact of SVR.

We conducted a cohort study of 8039 consecutive adult CHC patients seen at two medical centres in California between January 1997 and June 2016. Individual chart review confirmed CHC diagnosis.

Asian and Hispanic but not African American patients had significantly higher cirrhosis and HCC incidence than Caucasians. On multivariate analysis, Hispanic ethnicity was independently associated with increased cirrhosis (adjusted HR 1.37, CI, confidence interval 1.10-1.71, P=.006) and HCC risk (adjusted HR 1.47, CI 1.13-1.92, P=.004) compared to Caucasian. Asian ethnicity had a significant association with cirrhosis (adjusted HR 1.28, CI 1.02-1.61, P=.034) and HCC risk (adjusted HR 1.29, CI 0.94-1.77, P=.025). In patients who achieved SVR, Hispanic ethnicity was no longer independently associated with cirrhosis (adjusted HR 1.76, CI 0.66-4.71, P=.26) or HCC (adjusted HR 1.05, CI 0.27-4.08, P=.94); nor was Asian ethnicity (adjusted HR 0.62, CI 0.21-1.82, P=.38 for cirrhosis; 2.01, CI 0.63-6.36, P=.24 for HCC). Similar findings were observed with overall survival among the ethnicities by SVR status.

Hispanic and Asian ethnicity was independently associated with increased cirrhosis and HCC risk. Achieving an SVR eliminates the ethnic disparity in liver disease progression and overall survival between Hispanic and Asian vs Caucasian CHC patients.

Wednesday, August 2, 2017

Persistent Neuropsychiatric Impairment in HCV Patients Despite Clearance of the Virus?!

Persistent Neuropsychiatric Impairment in HCV Patients Despite Clearance of the Virus?!
Original article was published 9 February 2017 in Journal of Viral Hepatitis, the research article is open access over at Medscape, patient-friendly commentary published at Infectious Disease Advisor, discussion only provided below.

Many patients with HCV infection report disabling chronic fatigue--even after viral clearance. Might HCV be implicated in a virus infection-associated chronic fatigue syndrome?

Persistent Neuropsychiatric Impairment in HCV Patients Despite Clearance of the Virus?!
M. Dirks; H. Pflugrad; K. Haag; H. L. Tillmann; H. Wedemeyer; D. Arvanitis; H. Hecker; A. Tountopoulou; A. Goldbecker; H. Worthmann; K. Weissenborn
J Viral Hepat. 2017;24(7):541-550. 

Discussion Only
Full text article published @ Medscape 
To our knowledge the present study is the largest study concerning neuropsychiatric symptoms in PCR-positive and PCR-negative HCV-afflicted patients with only mild liver disease that combined the assessment of health-related quality of life with the assessment of chronic fatigue, mood disturbances and cognition.

The results of our study can be summarized as follows: (i) PCR+ and PCR− HCV-afflicted patients with only mild liver disease but neuropsychiatric symptoms do not differ with regard to the features and extent of these symptoms, (ii) chronic fatigue is the most frequent neuropsychiatric symptom and has the most significant impact on the patients' health-related quality of life, (iii) significant cognitive dysfunction is present in about one-third of the patients with neuropsychiatric symptoms and (iv) is not feigned by the presence of depression.

So far, the largest population sample related to cognitive function in HCV-afflicted patients was published by Fontana et al.[31] They analysed cognitive function in PCR−positive patients with advanced liver fibrosis (Ishak fibrosis score 3–6), who took part in the HALT-C trial—a prospective, randomized, controlled study of long-term pegylated interferon for chronic hepatitis C patients with advanced fibrosis who were nonresponders to prior interferon therapy. Two hundred and one patients were included of whom 38% had developed liver cirrhosis. Fifty-two per cent of their patients met DSM-IV criteria for a lifetime diagnosis of an alcohol use disorder, and 39% of subjects met DSM-IV criteria for a lifetime diagnosis of a drug use disorder. In analogy to our findings Fontana and co-workers reported that about 33% of their patients showed evidence of mild cognitive dysfunction. Domains predominantly affected were verbal recall and working memory. Of note and in line with our data, they did not find evidence for a significant effect of neither liver function nor grade of liver fibrosis or of former alcohol or drug abuse upon their neuropsychological results. Interestingly, the domains affected were congruent with those described in other studies upon cognitive dysfunction in HCV-afflicted patients but incongruent with the characteristic neuropsychological pattern of hepatic encephalopathy associated with liver cirrhosis.[32] Thus, there was clear evidence that cognitive dysfunction in the patients in Fontana's study was not due to hepatic encephalopathy, but instead probably due to HCV infection.

Our study included patients with mild liver disease, exclusively, thereby even further eliminating the confounding of advanced liver disease on brain function. Nevertheless, we found deficits in the recognition of words or figures in 45% and attention deficits in 30% of the patients. About 77% showed chronic fatigue, and 50%-60% mild to moderate anxiety and depression. Health-related quality of life correlated negatively with fatigue, as did the patients' attention ability. Of note, the patients' cognitive function was independent from their mood status. The significant correlation between attention test sum score and the fatigue and depression scores would indicate otherwise on the first view, multiple regression analysis, however, identified the extent of fatigue as the main and single independent predictor of attention deficit. The positive correlation between the attention test sum score and the LLW sum score relates to the fact that LLW tests working memory and learning ability and thus attentional function. Memory function in our patients did not show a correlation with either fatigue or depression scores and was even independent from the attention test performance, thus also indicating that cognitive dysfunction in the patients is independent from mood alterations.

Of note, we did not find a fundamental difference in the neuropsychiatric symptom profile considering the PCR status or treatment history.

Chronic fatigue has been identified as the most frequent complication of HCV infection years ago.[2] For a long time, however, the patients' complaints about disabling fatigue have not directly been linked to the virus. Symptoms were classified as reaction to the knowledge of being infected or as a consequence of advanced liver disease. Patients showing sustained response to antiviral therapy were and are still in general considered to be cured. Our data, however, show that the neuropsychiatric symptoms, if present, feature identical in PCR-positive and PCR-negative HCV-afflicted patients. Former studies showed similar alterations of brain metabolite levels, cerebral glucose utilization and dopaminergic neurotransmission in PCR-positive and PCR-negative patients, as well as a relationship between these parameters and the patients' cerebral function.[33–35] This indicates that clearance of the virus in the periphery is not equivalent to cure from neuropsychiatric sequelae of HCV infection. It has still to be clarified, for example, if quasispecies of the virus are able to persist within the brain after successful clearance in the periphery, or if the virus induces a neuroinflammatory response that carries on independent of the presence or absence of the virus. Recently, HCV RNA was detected in peripheral blood mononuclear cells (PBMCs) in patients with sustained viral response (SVR) 52–66 months after pegylated IFN and ribavirin therapy.[36] In addition, it has been shown that cure of HCV infection does not lead to complete restoration of the altered cytokine and chemokine milieu. According to a recent paper by Hengst and colleagues, several soluble inflammatory mediators that are suppressed in HCV patients before successful antiviral therapy remain suppressed thereafter.[37]

Patients in both PCR-negative groups were more impaired than those in the PCR-positive groups in this study. This, however, can reflect a selection bias, because PCR-negative patients without any further symptoms are less likely to present in a hepatitis outpatient clinic or to seek support in a patient support group and to take part in a study upon neuropsychiatric symptoms than PCR-negative patients with symptoms. The same aspect holds true of course also for PCR-positive patients and might lead to an overestimation of the frequency of neuropsychiatric symptoms in HCV patients.

Recent therapeutic studies were able to show that virus eradication results in clinically meaningful improvements in several HRQoL domains.[11–14] These studies also showed that improvement was likely to be achieved in physical but not in mental health scores. Based on these findings Bonkovsky et al.[14] suggested that HCV infection per se has an effect on emotional states. Accompanying cognitive deficits in HCV-infected patients, however, was suggested to result from underlying conditions such as anxiety and depression or use of psychotropic medications rather than from HCV infection itself.[14] This explanation is disproved by our findings as we did not observe a significant correlation between cognitive function and anxiety or depression and had excluded patients on psychotropic drugs. Comparing the results of patients who had been interferon/ribavirin exposed to those who had never been treated, we were able to show that the neuropsychiatric symptoms in formerly treated HCV-afflicted patients cannot be ascribed to interferon/ribavirin therapy.

Today we have growing evidence for HCV invasion into and replication within the brain.[38–42] Interestingly, evidence for virus replication was found in about 50% of the samples studied. That is nearly identical with the percentage of HCV patients with neuropsychiatric symptoms in population studies.[2,18,43] In a recent autopsy study, microglia and astrocytes were identified as host cells for the virus.[42] The alterations of magnetic resonance spectra of the brain of HCV patients suggested a neuroinflammatory response to the virus.[8–10,35] This assumption was supported by the finding of an activation of brain microglia cells in autopsy brain tissue from HCV-positive patients.[44] Therefore, evidence for microglia activation in patients with HCV−associated encephalopathy was searched using 11C- PK11195 positron emission tomography. 11C-PK11195 binds to the translocator protein (TSPO) which is located amongst others on the outer mitochondrial membrane of microglia, and which is expressed especially in activated microglia.[45,46] Indeed, microglia activation was observed compared to controls both in PCR-positive and in PCR-negative patients.[47,48] Differences in 11C-PK11195 binding, however, were found between patients with and without cognitive dysfunction. Preserved cognitive function was associated with significantly increased microglia activation indicating a neuroprotective role of microglia activation in the HCV−exposed patients.[48]

In our study, PCR+ and PCR− patients scored similarly in all assessed domains, while both patient groups scored significantly worse than the healthy controls. The data clearly show that neither the HRQOL, nor the extent of fatigue, nor cognitive or mental function in HCV-exposed patients depend on their PCR status. This finding is in line with earlier studies including large and representative cohorts of women infected through anti-D prophylaxis. In both cohorts, from Ireland[49] and from Germany,[43] fatigue was a frequently observed phenomenon, but unrelated to liver disease and virological status.

The observation that the neuropsychiatric syndrome in HCV-exposed patients is independent of the virus replication state as measured in the patients' blood is in favour of the hypothesis that the symptoms are unrelated to HCV infection. However, the development of an HCV infection triggered autoimmune process, which continues after clearance of the virus, or—alternatively—the possibility of a virus variant persisting in the brain should seriously be discussed. Considering the data upon virus infection-associated chronic fatigue syndrome HCV just appears to be more capable to induce this disorder than other viruses, while the clinical features are similar irrespective of the underlying cause.[50] It will be of outmost interest to observe whether sustained response to the new direct acting antivirals will be more effective with regard to neuropsychiatric manifestations of HCV than the interferon/ribavirin combination therapy.

Continue to full text article published @ Medscape
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No Hep B reactivation for resolved infection treated with direct-acting antivirals for Hep C

No Hep B reactivation for resolved infection treated with direct-acting antivirals for Hep C

Full Text Article Available Online @ Alimentary Pharmacology & Therapeutics
Following summary published @

Published ahead of print, the Alimentary Pharmacology & Therapeutics reports no evidence of hepatitis B virus reactivation in patients with resolved infection treated with direct-acting antivirals for hepatitis C in a large real-world cohort.

Hepatitis B virus (HBV) reactivation has been observed following interferon-based treatment in HBV/hepatitis C virus (HCV) co-infected patients.

Recent reports suggest that reactivation may also occur in both hepatitis B surface antigen (HBsAg)-positive and HBsAg-negative patients during HCV treatment with direct-acting antivirals.

Dr Vermehren and colleagues from Germany investigated the rate of patients with HBV reactivation during interferon-based and interferon-free HCV treatment in a large real-world cohort.

A total of 848 patients with chronic hepatitis C were treated with different combinations of direct-acting antivirals.

Among patients with available outcome and HBV data, there were 272 patients hepatitis B core antibody (HBcAb)-positive, and 536 were HBcAb-negative.

All HBcAb-positive patients were tested for HBV DNA at the end of direct-acting antiviral therapy and alanine transaminase (ALT) levels were frequently measured during therapy and follow-up.

The team found that 73% of HBsAg-negative/HBcAb-positive patients had elevated ALT levels at baseline, which declined to normal values in all but 18 patients, and no HBV reactivation was observed.

There were 8 patients that had detectable but not quantifiable HBV DNA at end of treatment, but none were associated with elevated ALT.

The research team observed that 5 of 9 HBsAg-positive/HBcAb-positive patients experienced transient or permanent HBV reactivation, 3 of whom required nucleotide treatment during or after direct-acting antiviral therapy.

Dr Vermehren's team concludes, "HBV reactivation was not observed in HBsAg-negative/HBcAb-positive patients but common in HBsAg-positive/HBcAb-positive patients treated with different combinations of direct-acting antivirals for HCV."

Aliment Pharmacol Ther 2017: Early view DOI: 10.1111/apt.14177

Kentucky - Syringe exchanges coupled with drug therapy, treatment could virtually eliminate hepatitis C

Syringe exchanges coupled with drug therapy, treatment could virtually eliminate hepatitis C
By Melissa Patrick
Kentucky Health News

Kentucky leads the nation in new infections of hepatitis C, a liver disease now driven mainly by intravenous drug use. It could be virtually eliminated, but that would require a committed strategy to increase syringe exchanges, medication-assisted therapies, and cutting treatment restrictions such as a ban on treating active intravenous drug users.

That was the overarching message to almost 300 people who attended the fourth annual Viral Hepatitis Conference in Lexington July 27. They also heard that Kentucky is working on all three fronts, but not going as far as some experts want when it comes to treating drug users.

Tuesday, August 1, 2017

Reining in Drug Prices: Easier Said than Done

Encouraging generics, ditching 'pay for delay,' easing regulations suggested

by Joyce Frieden, News Editor, MedPage Today August 01, 2017

WASHINGTON -- Some of the so-called solutions for reducing the price of prescription drugs are not as easy as they seem, experts said at a panel here hosted by the Alliance for Health Policy.

Ideas such as having the federal government negotiate drug prices or allowing importation of prescription drugs from other countries "sound good, but they're probably not going to work, or get through Congress," former House member Henry Waxman (D-Calif.) said at the event on Friday. "So we need to look at the problem in a more narrow way in order to get bipartisan support."

Steve Miller, MD, chief medical officer of Express Scripts, a pharmacy benefit manager, gave an example of his company's use of paying for value. "We started the price war for hepatitis C drugs; we were able to get the price down to an [incredible] extent," he said (The hepatitis C treatment Solvadi cost close to $100,000 in 2014). "The old treatment for hepatitis C was ribavirin and interferon; that used to be $35,000. We now have the price of the current crop of hepatitis C treatments at $35,000, which is cheaper than they are in Europe."

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On this blog
The controversy over expensive new drugs for hepatitis C
Link to research and news articles addressing the high cost of hepatitis C drugs; insurance restrictions - private insurers/Medicaid - and availability of generic versions/India, Egypt and other lower-income countries or through online "buyers clubs"  

Direct-acting antivirals successfully treating hepatitis C, says Public Health England

In Case You Missed It

Article Source
The Pharmaceutical Journal

Hepatitis C in the UK - 2017 report
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Direct-acting antivirals successfully treating hepatitis C, says Public Health England

A new report suggests early detection of the disease is key as treatment with direct-acting antiviral therapy in the initial stages has the best results.

Public Health England (PHE) is urging the public to get tested for hepatitis C after its latest figures revealed a fall in deaths from the disease, which it attributed to the introduction of direct-acting antiviral (DAA) therapy.

PHE’s annual report, published on 28 July 2017, estimated that around 200,000 people in the UK are unknowingly living with chronic hepatitis C, but it said that “revolutionary treatments” can successfully treat the disease in the vast majority of cases, with the best results in the earlier stages of the disease.

According to the report, Hepatitis C in the UK, people infected with the disease need to be found and treated as quickly as possible to sustain the recent nationwide drop in deaths from the condition.

The majority of cases in the UK are considered to be from marginalised and under-served groups in society, such as people who inject drugs.

Current data from PHE shows an estimated 10% reduction in mortality from hepatitis C-related end-stage liver disease and cancer in 2016, and the introduction of DAA drugs has resulted in a 50% reduction in need for liver transplantation for chronic hepatitis C infection.

Commenting on the report, Duncan Selbie, chief executive of PHE, said: “The recent fall in UK deaths looks likely to be the result of increased treatment with new direct-acting antiviral drugs, with an increase of nearly 50% over the past year, and of nearly 90% when compared with earlier years.
Sustaining increase in treatment

“Our ability to sustain this increase in treatment will ultimately be limited by our capacity to find and treat those who remain undiagnosed, and to help those who are diagnosed but untreated to engage with accessible treatment services.”

Helen Harris, clinical scientist at PHE’s Immunisation, Hepatitis and Blood Safety Department, said: “We strongly encourage anyone who may have been at risk of hepatitis C infection to get tested, whether or not they have any symptoms.

“We are hopeful that the increased access to improved treatments over recent years has contributed to the latest fall in deaths from severe hepatitis C-related liver disease. This, combined with interventions to prevent infection in the first place, can help us to achieve our vision of eliminating hepatitis C as a major public health threat in the UK.”

In June the Hepatitis C Trust criticised the results of a study carried out by the Cochrane Hepato-Biliary Group that cast doubt on the effectiveness of DAA drugs against hepatitis C.

Citation: The Pharmaceutical Journal, PJ July 2017 online, online | DOI: 10.1211/PJ.2017.20203312

FDA Approves Expanded Labeling for Epclusa® for Hepatitis C in Patients Co-Infected with HIV

U.S. FDA Approves Expanded Labeling for Epclusa® (Sofosbuvir/Velpatasvir) for the Treatment of Chronic Hepatitis C in Patients Co-Infected with HIV

- New Data for First Approved Pan-genotypic Once-Daily Single Tablet Regimen for Chronic Hepatitis C Virus Infection -

FOSTER CITY, Calif.--(BUSINESS WIRE)--Aug. 1, 2017-- Gilead Sciences, Inc. (NASDAQ: GILD) today announced that the U.S. Food and Drug Administration (FDA) has approved updated labeling for Epclusa® (sofosbuvir 400mg/velpatasvir 100mg), the first all-oral, pan-genotypic, once-daily single tablet regimen (STR) for the treatment of adults with chronic hepatitis C virus (HCV) infection, to include use in patients co-infected with HIV. Epclusa received regulatory approval for the treatment of adults with genotype 1-6 chronic HCV infection without cirrhosis or with compensated cirrhosis, or with decompensated cirrhosis in combination with ribavirin, in the United States on June 28, 2016.

Epclusa has a boxed warning in its product label regarding the risk of hepatitis B virus (HBV) reactivation in HCV/HBV co-infected patients. See below for important safety information.
"HCV co-infection remains a major cause of morbidity in HIV-infected individuals. With this expanded use, Epclusa provides co-infected patients with a much needed one-pill-a-day regimen that works across all HCV genotypes and is compatible with widely-used antiretroviral regimens," said David Wyles, M.D., Chief, Division of Infectious Disease, Denver Health Medical Center; Associate Professor of Medicine, University of Colorado School of Medicine. "With Epclusa, physicians have an important new treatment option for their HCV/HIV co-infected patients."

The supplemental new drug application (sNDA) was supported by data from the open-label, Phase 3 ASTRAL-5 study, which evaluated 12 weeks of treatment with Epclusa in 106 subjects with genotype 1-4 HCV infection who were co-infected with HIV and on stable antiretroviral therapy. In the study, 95 percent (101/106) of patients achieved the primary endpoint of SVR12, defined as an undetectable viral load 12 weeks after completing therapy.

The safety profile of Epclusa in HCV/HIV co-infected patients was similar to that observed in HCV mono-infected patients. The most common adverse events (in at least 10 percent of subjects) were fatigue (22 percent) and headache (10 percent).

"Epclusa has already helped further simplify HCV treatment among mono-infected patients, and we are pleased that HCV/HIV co-infected patients can benefit from this pan-genotypic single tablet regimen," said John F. Milligan, PhD, Gilead's President and Chief Executive Officer. "This approval advances the commitment we've made to the HCV and HIV communities to deliver innovative new treatments that address their unmet medical needs."

U.S. Patient Support Program
To support these patients and their families, Gilead's U.S. Support Path® program provides information regarding access and reimbursement coverage options to patients in the United States who need assistance with coverage for their medications, including Epclusa. Support Path conducts benefits investigations and provides patients with information regarding their insurance options.
Further, the Epclusa Co-pay Coupon Program offers co-pay assistance for eligible patients with private insurance who need assistance paying for out-of-pocket medication costs.
To learn more about Support Path for Epclusa, please visit or call 1-855-7-MYPATH (1-855-769-7284) between 9:00 a.m. and 8:00 p.m. (Eastern), Monday through Friday.

Global Availability
The prevalence of HCV genotypes varies regionally throughout the world. In resource-limited settings genotype testing can often be costly or unreliable, posing yet another barrier to treatment. As a pan-genotypic therapeutic option, Epclusa may help eliminate the need for genotype testing and has the potential to accelerate access to treatment for patients worldwide.
Gilead is committed to helping enable access to Epclusa around the world. Gilead works with a network of regional business partners, generic licensing partners and other stakeholders to expand treatment globally. Epclusa is already licensed to Gilead's 11 Indian manufacturing partners who produce and distribute generic versions of this medicine for 101 developing countries.

Important U.S. Safety Information for Epclusa

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with Epclusa. HBV reactivation has been reported in HCV/HBV co-infected patients who were undergoing or had completed treatment with HCV direct acting antivirals (DAAs) and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Cases have been reported in patients who are HBsAg positive, in patients with serologic evidence of resolved HBV, and also in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV DAAs may be increased in patients taking these other agents. Monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated.
  • If Epclusa is used in combination with ribavirin (RBV), all contraindications, warnings and precautions, in particular pregnancy avoidance, and adverse reactions to RBV also apply. Refer to RBV prescribing information.
Warnings and Precautions
  • Serious Symptomatic Bradycardia When Coadministered with Amiodarone: Amiodarone is not recommended for use with Epclusa due to the risk of symptomatic bradycardia, particularly in patients also taking beta blockers or with underlying cardiac comorbidities and/or with advanced liver disease. A fatal cardiac arrest was reported in a patient taking amiodarone who was coadministered a sofosbuvir containing regimen. In patients without alternative, viable treatment options, cardiac monitoring is recommended. Patients should seek immediate medical evaluation if they develop signs or symptoms of bradycardia.
  • Risk of Reduced Therapeutic Effect Due to Concomitant Use of Epclusa with P-gp Inducers and/or Moderate to Potent Inducers of CYP2B6, CYP2C8 or CYP3A4: Rifampin, St. John's wort, and carbamazepine are not recommended for use with Epclusa as they may significantly decrease sofosbuvir and/or velpatasvir plasma concentrations.
Adverse Reactions
  • The most common adverse reactions (=10%, all grades) with Epclusa were headache and fatigue; and when used with RBV in decompensated cirrhotics were fatigue, anemia, nausea, headache, insomnia, and diarrhea.
Drug Interactions
  • Coadministration of Epclusa is not recommended with topotecan due to increased concentrations of topotecan.
  • Coadministration of Epclusa is not recommended with proton-pump inhibitors, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, efavirenz, and tipranavir/ritonavir due to decreased concentrations of sofosbuvir and/or velpatasvir.
Consult the full Prescribing Information for Epclusa for more information on potentially significant drug interactions, including clinical comments.

About Gilead Sciences
Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company's mission is to advance the care of patients suffering from life-threatening diseases. Gilead has operations in more than 30 countries worldwide, with headquarters in Foster City, California.

Forward-Looking Statement
This press release includes forward-looking statements, within the meaning of the Private Securities Litigation Reform Act of 1995, that are subject to risks, uncertainties and other factors, including the risk that physicians may not see the benefits of prescribing Epclusa for the treatment of adults with chronic HCV infection, for expanded use in patients co-infected with HIV. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead's Quarterly Report on Form 10-Q for the quarter ended March 31, 2017, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. Full Prescribing Information for Epclusa, including BOXED WARNING, is available at

Epclusa is a registered trademark of Gilead Sciences, Inc., or its related companies.
For more information on Gilead Sciences, please visit the company's website at, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.