AASLD members at forefront to raise awareness of hepatitis B and C

Published on May 23, 2013 at 2:26 AM

Viral hepatitis is an asymptomatic disease affecting more than 5.3 million Americans. More than 75 percent of those with hepatitis C are unaware they have the virus.

Hepatitis B and C Testing and Awareness Day in the U.S. House of Representatives will take place at 10:00 am - 2:00 pm in the Rayburn Foyer of the Rayburn House Office Building in Washington, D.C.

The American Association for the Study of Liver Diseases (AASLD) is pleased to participate with the Congressional Hepatitis Caucus, the National Viral Hepatitis Roundtable, the Community Education Group, Hepatitis B Initiative of Washington DC, Caring Ambassadors Program, the National Alliance of State and Territorial AIDS Directors, the Association of Chinese American Physicians, and private industry to provide testing for hepatitis B and C.

In May 2011, the United States Department of Health and Human Services (HHS) released "Combating the Silent Epidemic of Viral Hepatitis: Action Plan for the Prevention, Care & Treatment of Viral Hepatitis." The plan runs through 2013, and AASLD -- the leading organization of scientists and healthcare professionals committed to preventing and curing liver disease -- welcomes the HHS announcement that it intends to update and renew the plan for 2014-2016.

Access to care and support of liver disease research are at the center of AASLD's advocacy efforts and Hepatitis Awareness Month and hepatitis testing events are necessary to make Americans aware that they can now be tested and treated for hepatitis C.

Research in the area of hepatitis C has led to FDA approval of two direct acting antiviral drugs for the treatment of hepatitis C, and numerous other direct acting antiviral drugs are in the development pipeline. AASLD looks forward to -- and its members work diligently to realize -- the day when an all-oral, interferon-free, shortened treatment can be used to eradicate the virus from patients with hepatitis C.

As research in hepatitis C continues, the fight against hepatitis B does so too, and AASLD members are at the forefront of these battles. We are proud to partner with the Centers for Disease Control and Prevention and others at HHS wherever there is an opportunity to raise awareness of both hepatitis B and C.

• May is Hepatitis Awareness Month.
• May 2013 is the second anniversary of the National Viral Hepatitis Action Plan.
• May 19, 2013, was the second annual Hepatitis Testing Day.
• May 23, 2013, is Hepatitis B and C Testing and Awareness Day in the U.S. House of Representatives.

SOURCE American Association for the Study of Liver Diseases

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FDA Rethinking Personalized Drug Trials

By David Pittman, Washington Correspondent, MedPage Today

Published: May 22, 2013

WASHINGTON -- The FDA will need to "turn the clinical trial paradigm on its head" in order to allow more specifically targeted, personalized drug therapies to get on the market faster, a top agency official said Tuesday.

"We are going to have to change the way drugs are developed. Period," said Janet Woodcock, MD, head of the FDA's Center for Drug Evaluation and Research.

Answering every question needed from regulators about targeted therapies -- such as who should receive the drug, at what dose, and with what expected side effects -- won't be possible in a traditional clinical trial, she explained at a luncheon hosted by the Personalized Medicine Coalition, a group of insurers, drugmakers and patient communities here whose goal is to "promote the understanding and adoption of personalized medicine concepts, services and products to benefit patients and the health system," according to its website.

Instead of embarking on traditional clinical trials, drugmakers and clinical investigators need to work in different ways to select patients for what will inevitably be smaller trials, she said.

"Ever smaller subsets of patients are being identified, and we're really going to have to put our heads together and figure out how do you study these small subsets of diseases," Woodcock said in a 45-minute speech on the FDA's efforts to advance the field. "What types of trials and development programs do you do? And when does a subset get so small that you're not going to be able to do a randomized trial?"

Advances in genomics has allowed drugmakers to develop not just a new breast cancer treatment, for example, but one that targets a specific genotype of that cancer like HER2, as was done with trastuzumab (Herceptin).

Anywhere from an eighth to half of companies' drug pipelines are targeted therapies, Woodcock said. About a third of new entities approved by the FDA last year had some type of genotyped biomarker in its marketing application.

Developments in cancer drugs, infectious diseases, and genetic disorders have led the way on such personalized therapies.

But in order to develop trials to test these drugs, the FDA and drug developers need a "new definition of clinical trials" that recognizes therapies will be targeted at subsets of conventionally defined diseases, Woodcock said.

Rather than doing a single trial in all patients with a particular disease, developers need to stratify patients into needed subsets based on certain biomarkers, she continued. Only then will trials be able to test the safety and effectiveness of their drug candidates.

The way trials were developed in the past should not influence or govern the way things are done in the future, Woodcock said.

For decades, the agency has requested two randomized, controlled, non-inferiority trials. But those may not be possible with the small number of patients possible in trials.

In order to identify these subset of patients -- which may be very few in number -- drugmakers may have to work together or work with third parties like patient advocacy groups to identify them, the FDA drug center head said.

"We haven't seen a lot of this so far," Woodcock said. "We're hoping that independent groups set up these trial networks and standing trials, so that then companies are comfortable coming together through a third party to do development of their drugs."

The personalized cystic fibrosis drug ivacaftor (Kalydeco), which treats the disease arising from the G551D-CFTR mutation, was developed through such a patient group network, Woodcock said.

But there are other challenges the agency and developers must tackle too.

Such targeted therapies have had difficulty receiving insurance coverage, in part because of their price. Woodcock noted this trend has slowed development of diagnostics that accompany such products.

Therefore, targeted therapies need to slow or stop chronic diseases and not just show a positive short-term benefit to silence critics. "If we can cure Hepatitis C, there's not going to be a peep from anybody because the cost effectiveness of that will be absolutely clear," she said. "Same with cancer."

The FDA is also thinking about how to translate prescribing information to providers, who want simple, easy-to-understand instructions.

"They want directions. They don't want education. They don't want to be taught genetics," Woodcock said. "They want [to know] 'what do I do. please tell me.' "

Therefore, diagnostics that accompany drugs and information in labeling needs to be detailed and accurate but also easily understood.

That path ahead won't be easy and will require a grand change in the way clinical trials are thought about by drug regulators and developers. "We're going into uncharted waters here," Woodcock said. "I think it's going to be a big challenge for everyone."

Source

Hepatitis C: A 21st Century Success Story (Op-Ed)

Credit: Dreamstime

Dr. David Bernstein, North Shore-LIJ Health System

Date: 22 May 2013 Time: 03:38 PM ET

Dr. David Bernstein is chief of the Division of Hepatology / Center for Liver Disease at the North Shore-LIJ Health System, and a professor of medicine at Hofstra North Shore-LIJ School of Medicine. He contributed this article to LiveScience's Expert Voices: Op-Ed & Insights.

Hepatitis C has been called a silent epidemic: As the most common blood-borne viral infection in the country, it affects more than 7 million Americans — yet, most don't know they have it. But the condition can lead to the development of cirrhosis and liver cancer, and is the leading indication for liver transplantation in the United States.

Baby boomers have the highest rate of hepatitis C infection, so the Centers for Disease Control and Prevention (CDC) recently recommended that all people born between 1945 and 1965 get tested at least once for it. People with other risk factors for hepatitis C (e.g., previous intravenous drug users, previous cocaine users, recipients of blood transfusions before 1992, and people with tattoos and body piercings in places other than the ears) should also get tested, regardless of age.

Once hepatitis C is diagnosed, it is curable, unlike other common blood-borne viruses , such as hepatitis B and HIV. Advances in hepatitis C therapies have been rapid. The first therapy for hepatitis C infection consisted of interferon injections alone, with a cure rate of less than 10 percent. In the mid-1990s, a pill called ribavirin was added to injectable interferon, and cure rates increased to about 40 percent. For more than 10 years, once-weekly injectable interferon plus oral ribavirin for a course of 24 to 48 weeks was the standard treatment method.

The high prevalence of hepatitis C has led to a considerable effort to improve cure rates with newer therapies. The first step was to understand the mechanism of hepatitis C viral replication. After researchers determined the disease's molecular structure, they identified the two main classes of enzymes involved in hepatitis C replication: protease and polymerase inhibitors. As a result of that research, direct-acting medications were manufactured to inhibit those enzymes — thus preventing replication and promoting higher cure rates.

In May 2011, the U.S. Food and Drug Administration approved the first new hepatitis C therapies in a decade. Two new oral agents — boceprevir and telaprevir, from the class of drugs called protease inhibitors — were approved for use in combination with pegylated interferon and ribavirin. These new, triple-therapy regimens have seen cure rates as high as 70 to 75 percent. Therapy lasts from 24 to 48 weeks. Boceprevir and telaprevir are both taken three times a day for a time period ranging from three months to 44 weeks, depending on clinical circumstance for each patient.

The new protease inhibitors increased efficacy — and side effects . Telaprevir is associated with a rash that generally appears in the first four to eight weeks of therapy, as well as anal pain that can manifest at any time during treatment. Most patients are easily treated with topical creams and antihistamine pills. Boceprevir is associated with a bad taste in the mouth in almost all patients — though this is more of an annoyance than a problem. Most patients barely notice it. Both telaprevir and boceprevir are associated with the development of significant anemia, which can limit their use. The anemia can lead to fatigue and may require the use of growth factors — compounds that affect cell growth, maturity and differentiation — to alleviate symptoms.

Since the approval of boceprevir and telaprevir, drug development has been progressing rapidly. Many studies are evaluating the use of second-generation protease inhibitors, polymerase inhibitors and NS5A inhibitors in various combinations to treat all different types of patients with hepatitis C. In addition to new agents, shorter durations of therapy (eight or 12 weeks) and interferon-free, all-oral regimens are in development.

It is highly probable that an all-oral regimen for the treatment of hepatitis C genotype 2 and 3 will become available late this year or in early 2014, with similar efficacy as that of interferon-based therapies, but with fewer side effects and a shorter course. It is also likely that a new, second-generation protease inhibitor — simeprevir — and a first-in-class oral nucleotide analogue polymerase inhibitor — sofosbuvir — will be approved in early 2014.

Both of those new agents are given once daily and will be approved for use in hepatitis C genotype 1 in combination with interferon and ribavirin. The treatment duration for the new simeprevir-containing regimen will likely be 24 to 48 weeks, while the regimen with sofosbuvir will likely last 12 weeks. Neither of those new agents have any significant side effects, and cure rates should be higher than currently approved triple therapies.

After simeprevir and sofosbuvir are approved, many even newer agents are likely to come to market. It seems clear that all-oral therapy for the treatment of genotype 1 should be available sometime in 2015 or 2016. Compared to current regimens, all of the newer therapies offer higher cure rates, shorter duration of therapy and fewer side effects. A lot of work is underway to determine the best possible therapy for specific groups of patients. For example, specific regimens will likely be developed for each genotype, for patients with cirrhosis, for patients with kidney disease and for those who have had a kidney transplant.

With any luck, in the next decade, medical science should be able to treat and cure more than 90 percent of hepatitis C patients. The greater challenge is identifying patients — because most remain undiagnosed — and educating medical providers about the new therapies. Hopefully, the CDC screening guidelines will help. In addition to their other advantages, the newer therapeutic regimens may prevent the development of cirrhosis, liver cancer and the need for liver transplantation. The treatment and cure of hepatitis C will be one of the 21st century's major medical success stories.

Bernstein's disclosures are as follows:

Clinical-trial sponsors: Abbott, BMS, Gilead, Janssen, Vertex, Merck, Genentech

Consultant/speaker bureau: Abbott, Gilead, Janssen, Vertex, Merck

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Frederick A. Nunes, MD, on trial results for difficult-to-treat patients with HCV

Provided by Healio

May 22, 2013

ORLANDO, Fla. — Frederick A. Nunes, MD, associate professor of medicine, at Penn Health Systems, discusses his presentation, “Interferon‐free Regimens of ABT‐450/r, ABT‐267, ABT‐333, and Ribavirin Achieve High Sustained Virologic Response 4 Weeks Post‐Treatment (SVR4) Rates in Patients With Chronic HCV Genotype 1 Regardless of Race, Ethnicity, or Other Baseline Characteristics” during Digestive Disease Week 2013.

Among HCV patients who are difficult to treat, including African-Americans, those with high BMI and insulin resistance, achieved a very high sustained response using three direct-acting antivirals and ribavirin, Nunes says.

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P. Patrick Basu, MD, comments on RESTRAINT C trial results

Provided by Healio

May 22, 2013

ORLANDO, Fla. — P. Patrick Basu, MD, assistant clinical professor of medicine at Columbia University College of Physicians and Surgeons; division chief, department of gastroenterology and GI endoscopy at North Shore University Hospital in Forest Hills, N.Y., discusses his presentation “Romiplostim’s Effect to Optimize SVR With Telaprevir, Ribavirin, and PEG Interferon-Alfa 2A in Thrombocytopenic Cirrhotics With Chronic Hepatitis C. A Placebo Controlled Prospective Clinical Trial: RESTRAINT C Trial.”

Source

Mindie H. Nguyen, MD, comments on demographics among hepatitis C patients

Provided by Healio

Added 2013-05-21

Mindie H. Nguyen, MD, MAS, associate professor of medicine at Stanford University School of Medicine. Discussing her poster Sa1069: High Prevalence of Hepatitis C Virus Infection (HCV) in Asian Americans in a Community Primary Care Clinic, during DDW 2013 in Orlando, Fla.

Mindie Nguyen, MD, on HCV demographics

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Eric J. Lawitz, MD, reviews COSMOS trial with HCV genotype 1 patients

Provided by Healio

May 22, 2013

ORLANDO, Fla. — Eric J. Lawitz, MD, of the Texas Liver Institute at the University of Texas, San Antonio, discusses his late-breaking poster “SVR Results of a Once Daily Regimen of Simeprevir (Tmc435) Plus Sofosbuvir (Gs-7977) With or Without Ribavirin (RBV) in HCV GT 1 Null Responders” at Digestive Disease Week 2013....

He reports encouraging results for SVR among patients who underwent a 12-week regimen of simeprevir and sofosbuvir and were previously null responders to peginterferon and ribavirin.

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Andrew Muir, MD, analyzes recent hepatitis C clinical trial results

Provided by Healio

May 22, 2013

ORLANDO, Fla. — Andrew Muir, MD, clinical director, hepatology at Duke University Medical Center, offers an update on the most current hepatitis C research that was presented at Digestive Disease Week 2013.

With many new drugs coming forward, Muir said he provides his patients with time frames on the availability of these medications, including the much-anticipated interferon-free regimens. By understanding the regimens, a patient’s liver disease and what’s right for them, he says individualizing plans allows clinicians to better guide patients on timelines and expectations.

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European Medicines Agency Validates Gilead’s Marketing Application for Sofosbuvir for the Treatment of Hepatitis C

-- Once-Daily Sofosbuvir will Receive an Accelerated Assessment by EMA;

Designation Granted to New Medicines of Major Public Health Interest --

FOSTER CITY, Calif.--(BUSINESS WIRE)--May. 21, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced that the company’s Marketing Authorisation Application (MAA) for sofosbuvir, a once-daily oral nucleotide analogue inhibitor for the treatment of chronic hepatitis C virus (HCV) infection, which was submitted to the European Medicines Agency (EMA) on April 17, 2013, has been fully validated and is now under assessment. The data submitted in this MAA support the use of sofosbuvir and ribavirin (RBV) as an all-oral therapy for patients with genotype 2 and 3 HCV infection, and for sofosbuvir in combination with RBV and pegylated interferon (peg-IFN) for treatment-naïve patients with genotype 1, 4, 5 and 6 HCV infection.

Chronic HCV is a major cause of liver cancer and liver transplantation in Europe and around the world. The current standard of care for HCV involves 24-48 weeks of therapy with RBV and peg-IFN, which has to be injected and is associated with significant side effects.

“The clinical and economic burden of untreated HCV is substantial and growing rapidly. An estimated five million Europeans are living with hepatitis C, the majority of whom have not yet been diagnosed or are not in care. In addition, many are not suited to receive the current treatment regimens,” said John C. Martin, PhD, Chairman and Chief Executive Officer of Gilead Sciences. “If approved, sofosbuvir has the potential to improve cure rates, while reducing the duration of HCV therapy and reducing or eliminating the need for interferon injections.”

The MAA for sofosbuvir is supported primarily by data from four Phase 3 studies, NEUTRINO, FISSION, POSITRON and FUSION, in which 12 or 16 weeks of sofosbuvir-based therapy was found to be superior or non-inferior to currently available treatment options or historical controls, based on the proportion of patients who had a sustained virologic response (HCV undetectable) 12 weeks after completing therapy (SVR12).

Review of the MAA will be conducted under the centralized licensing procedure, which, when finalized, provides one marketing authorization in all 27 member states of the European Union (EU). EMA has accepted Gilead’s request for accelerated assessment for sofosbuvir, a designation that is granted to new medicines of major public health interest. Although accelerated assessment could shorten EMA’s review time of sofosbuvir by approximately two months, it does not guarantee a positive opinion from the EMA’s Committee for Medicinal Products for Human Use (CHMP) or final approval by the European Commission. If approved, sofosbuvir could be available for marketing in the EU in the first half of 2014. Gilead submitted a U.S. regulatory application for sofosbuvir in April 2013.

Sofosbuvir is an investigational product and its safety and efficacy have not yet been established.

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 worldwide. Headquartered in Foster City, California, Gilead has operations in North America, Europe and Asia Pacific.

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 EMA, the U.S. Food and Drug Administration and other regulatory agencies may not approve sofosbuvir, and that any marketing approvals, if granted, may have significant limitations on its use. Further, additional studies of sofosbuvir, including in combination with other products, may produce unfavorable results. In addition, even if approved, Gilead may not be able to successfully commercialize sofosbuvir, and may make a strategic decision to discontinue its development if, for example, the market for the product fails to materialize as expected. 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, 2013, 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.

For more information on Gilead Sciences, please visit the company's website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

Source: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Cara Miller, 650-522-1616 (Media)

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Integrating mental health care into HIV care

Public release date: 21-May-2013

Contact: Fiona Godwin
fgodwin@plos.org
01-223-442-834
Public Library of Science

The integration of mental health interventions into HIV prevention and treatment platforms can reduce the opportunity costs of care and improve treatment outcomes, argues a new Policy Forum article published in this week's PLOS Medicine. Syvia Kaaya from the School of Medicine at the Muhimbili University of Health and Allied Sciences in Dar es Salaam, Tanzania and her international colleagues say that effective interventions exist for recognition and treatment of co-morbid mental disorders and can be implemented successfully by trained non- specialized providers in HIV care.

The authors say that interventions delivered by "task-sharing" would require "supportive supervision, monitoring, and feedback to inform quality improvement in comprehensive HIV/AIDS services providing mental health care" and that "multidisciplinary collaboration, coordination, and communication on common concerns are imperative for HIV services that integrate mental health care."

"Clinical depression, alcohol abuse, and HIV-associated neurocognitive disorders (HAND) are prevalent in people living with HIV and have negative consequences for HIV treatment outcomes," say the authors.

The five articles providing a global perspective on integrating mental health will be published weekly in PLOS Medicine beginning 30 April 2013.

###

Funding: LW's participation was supported in part by NIMH P20 MH086048. The sponsors had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: SM provides consultancy services at Mildmay Center (Uganda) for HIV care and for the Peter C Alderman Foundation (PCAF) for the care of Psycho-trauma victims. All other authors have declared that no competing interests exist.

Citation: Kaaya S, Eustache E, Lapidos-Salaiz I, Musisi S, Psaros C, et al. (2013) Grand Challenges: Improving HIV Treatment Outcomes by Integrating Interventions for Co-Morbid Mental Illness. PLoS Med 10(5): e1001447.doi:10.1371/journal.pmed.1001447

IN YOUR COVERAGE PLEASE USE THIS URL TO PROVIDE ACCESS TO THE FREELY AVAILABLE PAPER:

http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001447

Contact:

Sylvia Kaaya
Muhimbili University of Health and Allied Sciences,
Psychiatry
TANZANIA, UNITED REPUBLIC OF
skaaya@gmail.com

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No postings yet for HIV-positive Marines, sailors since policy change

By Matthew M. Burke

Stars and Stripes

Published: May 22, 2013

SASEBO NAVAL BASE, Japan — More than nine months have passed since the Navy decided to open up overseas and large-ship platform assignments to HIV-positive sailors and Marines, but not a single sailor has gotten such a posting.

The Navy’s Personnel Command is grappling with how to implement the instruction, which also covers blood-borne pathogens like hepatitis B and C.

Secretary of the Navy Ray Mabus handed down the policy in August 2012.

Personnel Command officials declined to comment on when the policy would actually take effect. Instructions can take time to implement, Personnel Command spokesman Lt. Cmdr. Rob Lyon told Stars and Stripes in an email.

“Navy Personnel Command recently completed a review of SECNAVINST 5300.30E, dealing with blood-borne pathogens, to ensure sailors affected will have the greatest opportunity to be successful, and any concerns by their receiving commands will be addressed,” Lyon said. “We will more than likely have more to discuss once the Milpersman article (implementation guidance) has been chopped by all parties.”

The policy effectively opened the assignments to HIV-positive sailors and Marines who are stable and have undetectable viral loads, which translates into minimal medical complications, Bureau of Medicine and Surgery spokeswoman Shoshona Pilip-Florea told Stars and Stripes in December.

The change was made possible because of medical advances that allow someone who contracts the Human Immunodeficiency Virus to live 20-30 years without adverse health effects with as little as one pill per day.

The implementation guidance gives medical personnel, detailers and receiving commanders a veto power for each request “based on the medical risks and needs of the Navy,” depending on whether the command in question could “support care,” Pilip-Florea said.Prospective recruits are still precluded from joining the services if they have the virus.

“The policy change better aligns the treatment of HIV with how other chronic illnesses are managed by Navy Medicine,” Pilip-Florea said. “In the case of HIV-positive servicemembers, these personnel and the services have put a lot of time and effort into their careers, and there is no medical reason for them not to be able to continue serving with pride.”

Pilip-Florea said the biggest change from the previous policy for HIV-positive sailors and Marines comes in added flexibility to case management. Those servicemembers would no longer be bound to stateside medical facilities and rules that dictated the frequency of clinical evaluations.

“The frequency of clinical evaluations for HIV-infected military personnel shall be determined by the member’s health status and by nationally accepted guidelines,” the instruction reads. “On a case-by-case basis, follow-up HIV evaluations may be performed at smaller naval medical treatment facilities with the results of those appointments being reported for tracking purposes.”

Pilip-Florea said Navy Medicine does not track cost data for specific conditions or long-term chronic illnesses so treatment costs — stateside versus overseas — are not known.

The Navy policy is unique, officials from the other service branches said.

The Army prohibits HIV-positive soldiers from being deployed or assigned overseas, according to Col. Andrew Wiesen, Western Region Medical Center’s chief of preventive medicine and the Army Surgeon General’s preventive medicine consultant. Any soldier found to be HIV positive while overseas will be reassigned stateside.

There are numerous reasons for the Army’s policy, including host-nation restrictions, the incompatibility of medical treatment and supply of medications with deployment, and protection of the blood supply, Wiesen said. Soldiers are often asked to donate blood in emergencies, and testing is not always reliable or complete in a deployed setting.

The Air Force also limits HIV-positive airmen to stateside assignments, according to spokeswoman Donna Tinsley. However, active-duty airmen can apply for a waiver if the receiving unit can provide the needed care.

“Essentially if the OCONUS (outside the continental United States) base is in need of the position and willing to take on the member and can provide adequate care, then it’s more likely to get accepted,” she said.

However, waivers are frowned upon, Air Force officials said. HIV-positive airmen are prohibited from donating blood.

“A major concern regarding deployment would be blood donation,” Air Force Capt. Candice Ismirle said. “Refusal to do so in cases of mass casualties, etc., will cause other members to question why and may make it difficult for the patient to keep their diagnosis confidential. Also, if there was pressure to donate blood and the patient did so, there could be HIV transmission in the deployed setting.”

Ismirle said all deploying airmen must be free of medical conditions that require special appliances, frequent treatment or follow-up by medical specialists or sub-specialists. The virus is disqualifying and requires a waiver to remain on flying status.

The Navy addressed the issue as HIV rates have risen steadily over much of the U.S. military in recent years. The Navy began testing for HIV antibodies in 1985.

The Navy found 128 HIV-positive sailors in 1992 and 315 in 2012, including 250 on active duty, Pilip-Florea said.

The Marine Corps had 90 HIV-positive Marines in 2012 — 71 on active duty — and the Air Force had 210 on active duty, officials said.

The Army could not provide up-to-date figures due to a transition between who keeps the figures, spokeswoman Margaret Tippy said. However, in 2008 there were more diagnoses than in any year since 1995, according to an Armed Forces Health Surveillance Center report from August.

Rates have remained high, the report said. In 2012, there were 333 active-duty HIV-positive soldiers.

OutServe, an association of active LGBT military personnel, declined to comment when reached by Stars and Stripes on Monday. The group applauded the effort when it was announced last year.

For more information, see the Secretary of the Navy instruction at http://doni.daps.dla.mil/Directives/05000%20General%20Management%20Security%20and%20Safety%20Services/05-300%20Manpower%20Personnel%20Support/5300.30E.pdf.

burke.matt@stripes.com

Source

Interferon-free, treat-all approach cost effective, beneficial for chronic HCV

Provided by Healio

May 21, 2013

ORLANDO, Fla. — An orally administered, interferon-free regimen with a treat-all approach for patients with chronic hepatitis C may be more beneficial and more cost effective than interferon-based triple therapy, according to data presented at Digestive Disease Week.

Researchers used a decision analytic Markov model to compare four methods of treatment for chronic HCV genotype 1: Triple therapy with pegylated interferon, ribavirin and a direct-acting antiviral (DAA) with (method 1) or without biopsy guidance (method 2); and an orally administered, interferon-free regimen with (method 3) or without biopsy guidance (method 4). The methods that incorporated biopsy began treatment at fibrosis stage F2 – F4, with repeated biopsies every 5 years until patients were aged 70 years.

A treatment-naive, 50 year-old patient served as a reference case. Investigators based treatment outcomes for methods 3 and 4 on study results presented at scientific meetings, and baseline cost and utility for methods 3 and 4 were calibrated to match triple therapy.

“As all-oral regimens are in the process of being developed by various pharmaceutical and biotechnology companies, interest has been focused on efficacy and side-effect profiles of these therapies,” researcher Heshaam M. Mir, MD, director of research in the Liver & Obesity program at Inova Fairfax Hospital in Falls Church, Va., told Healio.com. “We did not see a great deal published in the literature nor presented at the major liver conferences discussing the economic impact of these all-oral regimens. We thought it would be an area of interest for the medical community.”

Method 4 was the most cost-effective approach, with an incremental cost-effectiveness ratio (ICER) of $16,289 per quality-adjusted life-year (QALY). Departure from baseline cost and utility of oral therapy did not raise the ICER above $50,000/QALY for this approach. This treatment also presented the lowest risk for developing cirrhosis (6.8%), decompensation or hepatocellular carcinoma (11%) and transplantation (2.7%) and was linked to the largest number of QALYs (18.351) compared with the other methods.

“A validated Markov model showed that an all-oral, interferon-free, treat-all regimen was the most cost-effective approach for treating chronic hepatitis C genotype 1 patients,” Mir said. “In addition to the economic advantage, it reduced the number of chronic hepatitis C patients reaching advanced liver disease, and increased life expectancy.”

Disclosure: Researcher Zobair M. Younossi reported serving on advisory committees/review panels for Salix Pharmaceuticals, Vertex Pharmaceuticals, Tibotec and GlaxoSmithKline, along with consulting services for Gilead Sciences and Conatus Pharmaceuticals.

For more information:

Younossi ZM. Sa1067: Interferon-Based and Interferon-Free Regimens for Patients with Chronic Hepatitis C, Genotype 1: Potential Cost-Effectiveness of Biopsy-Guided Treatment Versus Treat All Strategies. Presented at: Digestive Disease Week 2013; May 18-21, Orlando, Fla.

Source

Low Potassium Linked with Liver Disease

By Kristina Fiore, Staff Writer, MedPage Today

Published: May 21, 2013

Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania

Action Points

• Note that this cross-sectional study demonstrated an association between non-alcoholic fatty liver disease and lower potassium levels in a Chinese population.
• Be aware that the mean potassium difference between those with and without NAFLD was extremely small, made significant due to the large sample size.

Patients with non-alcoholic fatty liver disease (NAFLD) also had low potassium levels, researchers in China found.

In a population-based, cross-sectional study, patients with NAFLD had significantly lower serum potassium levels than those who did not have the liver condition (4.09 mM versus 4.14 mM, P<0.0001), Guang Ning, MD, of Shanghai Jiao-Tong University School of Medicine, and colleagues reported online in Clinical Endocrinology.

NAFLD has become an increasing burden on the healthcare system in recent years, so researchers have been interested in identifying risk factors for the condition, particularly with regard to environmental exposures, they noted in their introduction.

Some studies have shown that lack of potassium -- needed for normal cellular function and metabolic balance -- may contribute to various metabolic disorders, including insulin resistance, which may ultimately increase the risk of NAFLD.

To more closely assess the relationship between serum potassium and NAFLD, the researchers enrolled 8,592 Chinese patients -- 2,663 men and 5,929 women -- in their study. Three out of 10 patients in the overall cohort (30.3%) had NAFLD, with the prevalence gradually decreasing across increasing serum potassium quartiles.

Not only did those with NAFLD have significantly lower serum potassium levels than those without, but the prevalence of NAFLD in patients with hypokalemia was significantly higher than that seen in patients with normal serum potassium (40.5% versus 29.6%, P<0.0001).

Patients with lower serum potassium levels also had a larger waist circumference and more severe insulin resistance, and these associations held in multivariate linear regression analyses, they reported.

Compared with patients in the highest quartile of serum potassium, those in the lowest quartile had a higher risk of:

• NAFLD (OR 1.33, 95% CI 1.11-1.60)
• Insulin resistance (OR 1.81, 95% CI 1.49-2.19)
• Central obesity (OR 1.58, 95% CI 1.30-1.93)

In adjusted subgroup analyses, the researchers also found a significant relationship between serum potassium levels and the following factors:

• Female sex (OR 1.11, 95% CI 1.03-1.19, P=0.006)
• Younger age (OR 1.13, 95% CI 1.04-1.23, P=0.005)
• Central obesity (OR 1.16, 95% CI 1.07-1.25, P=0.0001)
• Insulin resistance (OR 1.17, 95% CI 1.06-1.30, P=0.003)

One potential mechanism linking low potassium levels with NAFLD is insulin resistance, the researchers said. Potassium depletion could cause low nitric oxide levels and endothelial dysfunction, they noted, which could ultimately lead to insulin resistance, as well as hypertriglyceridemia and glucose intolerance.

The study was limited, however, because NAFLD was diagnosed via ultrasound, instead of the gold standard of liver biopsy, and by the fact that the researchers did not assess dietary potassium intake.

Still, the researchers concluded that decreased serum potassium is associated with the prevalence of NAFLD and that insulin resistance and central obesity may play an important role in this association.

They called for further observational studies and clinical trials to determine whether correcting potassium deficiency can effectively reduce the incidence of NAFLD.

The study was supported by the Ministry of Health of China, the National Natural Science Foundation of China, and the Shanghai New Excellent Youth Program.

The researchers reported no conflicts of interest.

Primary source: Clinical Endocrinology
Source reference:
Sun K, et al "Low serum potassium level is associated with non-alcoholic fatty liver disease and its related metabolic disorders" Clinical Endocrinol 2013; DOI: 10.1111/cen.12168.

Source

Baby Boomers Urged to Get Tested for Hepatitis C Virus

Tue May 21, 2013 11:45am EDT

Saint Luke's Liver Disease Management Center says testing is key to saving lives, 'silent infection' rampant among baby boomers

PR Newswire

KANSAS CITY, Mo., May 21, 2013

KANSAS CITY, Mo., May 21, 2013 /PRNewswire-USNewswire/ -- If you're a baby boomer, you may not know that odds are high that you're carrying the hepatitis C virus, putting yourself at risk for illness that can range from minor to life threatening.

Hepatitis C is a contagious disease affecting primarily the liver, caused by the hepatitis C virus (HCV). The disease can range in severity from a mild illness lasting a few weeks, to a serious, lifelong condition that can lead to cirrhosis of the liver or liver cancer. The virus is transmitted through contact with the blood of an infected person.

Liver specialists at Saint Luke's Liver Disease Management Center join experts at the National Viral Hepatitis Roundtable in urging people born from 1945 to 1965 to get screened. "Most people with chronic HCV have no symptoms and are completely unaware they carry this 'silent' virus," said Frederic Regenstein, M.D., medical director, Saint Luke's Liver Disease Management Center. "It is vital that boomers and other populations at increased risk for hepatitis C get tested, and that they receive appropriate testing, including a follow up test when needed.

"Without appropriate testing, those with hepatitis C are less likely to learn about their infection and get the critical care and treatment that they need in order to prevent cancer, and other serious health consequences. May is National Hepatitis Awareness Month, and a perfect time to look into screening," Dr. Regenstein added.

A new report from the Centers for Disease Control (CDC) underscores the severe impact of hepatitis C among baby boomers (individuals born from 1945 through 1965). Baby boomers accounted for 67 percent of all reported hepatitis C cases and 72 percent of all reported deaths among persons with hepatitis C. The CDC recommends that all baby boomers get tested for hepatitis C.

The recent CDC data comes from enhanced hepatitis C surveillance in eight areas across the country. The findings indicate that half of those identified as having a positive hepatitis C antibody blood test reported to the health department also had the appropriate follow-up testing to determine if they are still infected. The other half did not have a follow-up test reported. Without the hepatitis C follow-up test, individuals do not know if they still have hepatitis C and cannot get the care and treatment they need. In this study, deaths were higher among those who did not have a follow-up test reported to the health department.

Left untreated, hepatitis C can cause serious liver damage, including liver cancer – the fastest-rising cause of cancer-related death in the U.S. In fact, deaths from hepatitis C-related illness, such as liver failure and liver cancer, have nearly doubled over the past decade, now accounting for more than 15,000 deaths in the U.S. each year. The CDC estimates that testing baby boomers for hepatitis C could identify more than 800,000 additional people with hepatitis C and save more than 120,000 lives.

According to the updated guidance, individuals tested for hepatitis C should receive a screening blood test, called an antibody test, in order to determine if the person has ever been infected with the hepatitis C virus. For those with a positive hepatitis C antibody test, a follow-up test is needed to determine if a person is still infected. In order to help ensure that patients are properly diagnosed, it is critical that providers conduct follow-up testing to ensure they receive life-saving care and treatment.

About Saint Luke's Liver Disease Management Center
At Saint Luke's Liver Disease Management Center, patients throughout the Midwest and across the United States have access to liver disease treatment options provided by a multidisciplinary physician group. From preventive care to liver transplantation, Saint Luke's provides a full range of services for patients with disorders of the liver, bile ducts, and pancreas.

Screenings are available; check local health departments for information.

SOURCE Saint Luke's Health System

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Is the HCV Pipeline Heading in the Right Direction?

Gastroenterology
Volume 144, Issue 3 , Pages 482-485, March 2013

Andrew Aronsohn

Andrew J. Muir

Tracy Swan

Donald Jensen

University of Chicago Medical Center, Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition, Center for Liver Diseases, Chicago, Illinois

Division of Gastroenterology and Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina

Treatment Action Group, New York, New York

University of Chicago Medical Center, Department of Medicine, Section of Gastroenterology, Hepatology and Nutrition, Center for Liver Diseases, Chicago, Illinois

published online 24 January 2013.

Hepatitis C (HCV) is a global health concern, with >180 million people infected worldwide. Advances in HCV therapy do not necessarily result in improvement of patient outcomes unless specific patient needs and therapeutic options are incorporated into development plans. In this commentary, we explore the lessons learned from the first generation of direct-acting antivirals (DAAs) and apply this insight to optimize delivery, safety, and efficacy to patients who will receive future generation of DAAs.

Lessons Learned From the First-Generation DAAs

The release of boceprevir and telaprevir in May 2011 marked a new era in HCV therapy. For many patients with genotype 1 HCV, DAA-based therapy has offered a significant improvement from previous standard of care.¹, ² However, first-generation DAA-based therapy is not a panacea, and to date, many patients remain untreated. Identification of the therapeutic need of at-risk patients will be of increasing importance as new HCV medications are under development.

Access to Care

In an era where a significant proportion of patients can now be cured of HCV, lack of adequate awareness, screening, access to care, and affordability of therapy persist; therefore, many infected patients remain both undiagnosed and untreated. Patients with limited resources, including those from developing countries with limited access to medical care, are among those with the highest prevalence of HCV and are unlikely to benefit from advances in HCV therapy.³ Reduction of HCV-related burden of disease will be realized only if a global infrastructure is in place to allow for cost-effective screening and delivery of HCV care. First, in resource-limited regions, consideration should be given to allocate therapy to patients based on need such as those with more advanced disease. Targeting effective therapy on a global scale is not a “one size fits all” approach. Patients who reside in resource-limited regions may not have access to the newest generations of DAA therapy and creative approaches for therapy that control cost should be sought. For example, in East Asian countries with a high prevalence of interleukin (IL)-28b CC genotype, focus on improvements in screening, and treatment with peginterferon alfa/ribavirin (PEG/RBV) may yield more overall benefit than attempting to pay for increasingly expensive DAA regimens that offer relatively small improvements in efficacy. Next, policy promoting effective linkage to care will be needed to ensure access to HCV care for all patients. This type of policy would include increases in mid-level providers specializing in HCV treatment, expansion of HCV treatment into the realm of primary care, and improvement in physician education along with incentivizing HCV care. Finally, ongoing research should prioritize simplified therapeutic algorithms that reduce the cost of initial evaluation and monitoring during therapy.

Currently Underserved Populations

Cirrhosis

Cirrhosis is becoming increasingly common among patients with HCV.⁴ Recently reported data from the CUPIC (Compassionate Use of Protease Inhibitors in Viral C Cirrhosis) cohort, a French early access program consisting of cirrhotic nonresponders, revealed poor tolerability of telaprevir and boceprevir-based treatment.⁵ A 16-week interim analysis reporting data from 292 patients receiving telaprevir and 205 patients receiving boceprevir showed significantly more patients with serious adverse events, including 6 deaths, when compared with published clinical trials (32.7%–45.2% SAE in CUPIC versus 9%–14% in clinical trials).⁵ Ongoing development programs should prioritize identification of features predictive of good treatment outcomes as well as development of better tolerated treatment regimens for cirrhotic patients.

HIV coinfection

HIV/HCV coinfection carries increased risk of progression to fibrosis and decompensation compared with the monoinfection.⁶ Although small phase II studies have shown improved efficacy and acceptable safety profiles in telaprevir- or boceprevir-based therapy in this population, treatment remains off label in coinfected patients and treatment decisions are currently being based on limited data.⁷, ⁸ Despite these limitations, off-label use will continue to occur to provide therapy to those most in need. Drug development programs should prioritize early and robust study of drug–drug interactions (DDI), ideally in parallel with phase II studies. Efforts should also be made to obtain labeling that extends to the HIV/HCV coinfected population because this will likely be necessary for widespread reimbursement. Rapid development and dissemination of treatment guidelines by specialty societies will also be important in guiding treatment decisions and reimbursement.

Post liver transplantation

HCV treatment with PEG/RBV in the post liver transplant population has yielded suboptimal results owing to low sustained virologic response rates, poor tolerability, and adverse events such as acute rejection.⁹ Unfortunately, extensive DDI with commonly used immunosuppressants have hindered the use of first-generation DAAs in this population (70-fold increase in tacrolimus concentration and 4.6-fold increase in cyclosporine concentration when administered with telaprevir).¹⁰ Many transplant centers have devised internal protocols using DAA-based treatment by extrapolating data from pharmacokinetic studies in an effort to make treatment as safe as possible. Although investigation to optimize the current treatment regimen is ongoing and of importance, first-generation DAAs may not be durable agents in this population, and prospective studies using newer generation DAAs, ideally without need for interferon, should be aggressively pursued.

Patients with medical comorbidities

Patients with multiple medical comorbidities are unlikely to be candidates for telaprevir- or boceprevir-based therapy owing to concerns over tolerability and a relative paucity of robust DDI data available for patients on multiple medications. Polypharmacy in the setting of multiple comorbidities is especially prevalent in older patients. These patients are at increased risk of HCV-related morbidity and mortality and have unique therapeutic needs that are not fully addressed by currently available HCV therapy. In addition, HCV has a high prevalence among patients with chronic kidney disease and is an independent risk factor for mortality in patients who are undergoing hemodialysis.¹¹ Currently, there are no published efficacy, pharmacokinetic, or safety data for the use of telaprevir or boceprevir given in combination with PEG/RBV in patients with severe chronic kidney disease.¹² Ribavirin is renally cleared and therefore carries increased risk in this patient population. Consideration should be given to devising dosing schedules based on renal clearance with DAA regimens.

The Next Generation of HCV Therapy

Ongoing clinical trials hold considerable promise for improvements in HCV therapy. Newer NS3/4A protease inhibitors, NS4B inhibitors, NS5A inhibitors, NS5B polymerase inhibitors, lambda interferon, and cyclophilin inhibitors are currently under development with hopes to deliver effective, safe and, shorter duration of therapy when compared with current standard of care (Table 1).¹³, ¹⁴, ¹⁵, ¹⁶, ¹⁷, ¹⁸, ¹⁹, ²⁰, ²¹ Agents featuring increased potency that allow for simultaneous targeting of various aspects of HCV replication using multiple agents will likely result in interferon-free therapy.

Table 1. Direct-Acting Antiviral Agents Currently in Phase 3 Trials

Drug	Type of agent	Interferon-containing regimen	Genotype	Response in phase II trials	Anticipated completion of phase III trials
Simeprevir (TMC 435)13	Protease inhibitor	Yes	1	75%–86% SVR 24 in treatment naive	January 2013
Faldaprevir (BI 201335)14	Protease inhibitor	Yes	1	71%–83% SVR 24 in treatment naive	February 2014
BI 20712715	NS5B inhibitor (given in combination with faldaprevir)	No	1	52%–69% SVR 12 in treatment naive	August 2015
Daclatasvir (BMS 790052)16	NS5a inhibitor	Yes	1	64%–65% SVR12 in treatment naive	January 2014
Asunaprevir (BMS 650032)17	Protease inhibitor (given in combination with daclatasvir)	No	1	63%–87% SVR4 in null responders	July 2014
Sofosbuvir (GS 7977)18, 19	Nucleotide polymerase inhibitor	Yes	1	90% SVR 12 in treatment naive	July 2013
		No	2,3	100% SVR in treatment naive	July 2013
GS 588520	NS5a inhibitor (given in combination with sofosbuvir)	No	1	No SVR data available	Dec 2014
ABT-450/r, ABT 267, ABT-33321	Protease inhibitor, NS5A inhibitor, non-nucleoside polymerase inhibitor	No	1	SVR 85%–99% in treatment naive/null responders	October 2014

SVR, sustained virologic response.

Anticipated Challenges

Will All Patients Be Able to Be Treated Without Interferon?

Interferon-free HCV therapy will represent a breakthrough in HCV treatment. Trials to date are encouraging, but have begun to reveal important interactions between drug, host, and virus that need to be better understood before interferon-free therapy becomes a mainstay of treatment. Previously unidentified host and viral characteristics may create a requirement for interferon-based therapy for some, raising the possibility that all oral regimens may not be appropriate for all patients. In addition, the cost of newly developed interferon-free regimens may be prohibitive, especially in many resource-limited regions of the world. Enthusiasm over the possibility of an “all-oral” cure for HCV must be balanced with realization that cost of therapy will create a disparity among those who can receive interferon-free therapy and those who do not have access. HCV will carry an extensive global burden of disease, even in an interferon-free era, if efforts are not made to diminish this disparity.

Off-Label Prescribing

First-generation DAAs are already being used off label to treat HIV coinfected patients and post liver transplant patients with significant HCV recurrence. Future availability of multiple DAAs with unique antiviral mechanisms may lead to “mixing and matching” therapeutic combinations that have yet to be thoroughly investigated. Off-label interferon-free combinations with limited supporting data may lead to unintended adverse events, emergence of viral resistance, and missed opportunities to treat with available therapy that is known to be highly effective and safe. Patients with decompensated cirrhosis and/or renal insufficiency are examples of patients with significant need for therapy; however, physiologic response to exposure of new DAAs with or without interferon is unpredictable. Treatment with future DAA regimens off label, without appropriate pharmacokinetic and dosing studies, may pose a significant risk to patients. Despite these risks, off-label prescribing will likely occur; therefore, it should be acknowledged and efforts should be made to reduce risk to patients. First, education of patients and providers is essential to gain an understanding of the risks of off-label prescribing. Next, for patients with no other options except off-label treatment, efforts should be made to collaborate and report experience of safety and outcomes. Finally, marketing concerns may dictate access to optimal combination therapy. Even if off-label regimens are promising, payers may not be willing to offer reimbursement. Public–private research partnerships to facilitate development of best-in-class regimens from different sponsors should be considered to encourage clinical collaboration between pharmaceutical companies.

Focusing Drug Development on Patients in Need

Clinical trials focusing on patients with few comorbidities are important to show efficacy and safety; however, because sustained virologic response rates using newer agents approach and exceed 90% in younger, healthy patients with no cirrhosis, we risk creating an oversaturated market for these patients while struggling to treat patients with limited resources and with more extensive liver disease and comorbidities. This disparity has already emerged since approval of the first-generation of DAAs and is at risk of further propagation unless specific attention is given to these underserved populations. Small, open-label studies should be conducted in parallel with phase III, for sicker patients who are ineligible for clinical trials. These trials would offer potentially life-saving treatment and would begin to characterize risks and benefits of different treatment regimens in currently underserved populations. In addition, the robust HCV pipeline comes at a cost. Money spent on research and development will ultimately be passed on to patients and our health care system overall. Payers may not cover costs of incremental improvements of medical therapy once standard of care treatment reaches an acceptable safety and efficacy profile. We should be conscious of reaching a point of diminishing returns in patients with high potential of cure and redirect research effort and funding to benefit those in need including those without access to any DAAs.

Hopes and Expectations: Overcoming Disparities in HCV Therapy

What can be done to ensure the HCV pipeline is heading in the right direction? Focus on appropriate allocation of therapy and accessibility to these resources is key. Large, multicenter, prospective, observational studies such as PEGBase, HCV-TARGET, CUPIC, and ANRS CO13 HEPAVIH, all of which aim to gather data from thousands of patients treated with triple therapy since the approval of telaprevir and boceprevir, are already underway and will be crucial in capturing data that is missing from published clinical trials. Because these observational registries obtain data from many providers from multiple sites, the quality of data should be carefully assessed. Standardization of data entry and judicious quality assurance monitoring, preferably though a centralized site, should be employed to ensure reliable and useful data are available. Continued involvement of key stakeholders such as advocacy and patient groups is essential to ensure that vulnerable and underserved populations have appropriate representation. In addition, both the need and potential danger of off-label prescribing of HCV therapy should be acknowledged with steps taken to allow for the safest possible outcomes. Finally, we should not assume that in upcoming years all patients will have access to HCV treatment. HCV is a global epidemic and many patients in resource-limited countries will not have access to DAA-based therapy. Efforts to develop a cost-effective treatment strategy for these populations is essential.

Advances in HCV therapy will bring new challenges. Success of the upcoming generations of DAAs will not be measured in incremental improvements of sustained virologic response, but rather by the availability of treatment options and accessibility to care for all patients infected with HCV.

References

Copyright

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30 Years of HIV: Looking Back, Looking Ahead

By Michael Smith, North American Correspondent, MedPage Today

Published: May 20, 2013

There was no fanfare on May 20, 1983 when Science published what is undoubtedly among the most important medical papers of the 20th century.

In the usual dry prose, researchers from the Institut Pasteur in Paris described a new retrovirus, which they dubbed lymphoadenopathy associated virus, or LAV.

It was, they reported, a "typical type-C RNA tumor virus" with a tropism for T-lymphocytes and was similar to -- but clearly distinct from -- human T-cell leukemia viruses, which had recently been discovered.

Today, we know it simply as HIV.

That paper made very little immediate impression, according to Françoise Barré-Sinoussi, PhD, of the Pasteur institute, who was the lead author and who later shared the 2008 Nobel prize in medicine for the discovery with the senior author Luc Montagnier, PhD.

Partly that was because HIV/AIDS -- although mysterious and deadly -- was not yet seen as a global threat.

Finding the virus "was not just an academic problem," Barré-Sinoussi told MedPage Today. "But there were only a few cases and we did not yet have the idea of the magnitude of the infection, the magnitude of the epidemic."

And the scientific community wanted more before breaking out the champagne. "We had to accumulate more data about the links between the virus itself and the disease," she said.

For those studying the issue, "it was a very important paper," commented Anthony Fauci, MD, director of the National Institute for Allergy and Infectious Diseases.

But it wasn't a "slam-dunk," he told MedPage Today. "Although it was clear they had isolated the virus ... there was no way to definitively diagnose people who were presenting at hospitals" so there was a missing link.

It was still necessary to demonstrate epidemiological links between the virus and people with AIDS, a demonstration that came the next year with papers by Robert Gallo, MD, then at the National Cancer Institute, and colleagues, Fauci said.

That research provided "epidemiological and serological proof that the virus was unequivocally associated with the disease that we were just then starting to call AIDS," he said.

But as that data accumulated, it became evident that French discovery was indeed significant -- the cause of the disease was finally known. Researchers optimistically talked about vaccines and cures as if they would be -- not easy, perhaps -- but not out of reach.

This week in Paris, the Pasteur institute will play host to an international symposium to mark the 30th anniversary of that discovery and there is a renewed sense of optimism about the pandemic.

But there is also an understanding that HIV remains a tough challenge, Fauci said. He is to deliver a keynote talk and part of its title sums up the past three decades of HIV/AIDS research: "much accomplished, much to do."

Among the "much to do," Fauci said, is to crack the tough problems of a vaccine and a cure -- the same tough problems that have dogged the field since 1983.

At that time, he said, "we didn't realize that HIV was such a difficult virus" and it wasn't yet clear that it would not easily surrender to medical science.

On the vaccine front, for instance, the usual approach is to try to mimic nature -- cause an immune response that first halts, then clears, and then protects against the disease.

But in HIV, that's not nature's way, Fauci noted. With vanishingly few exceptions, no one mounts an immune response that stops, clears, and protects against HIV.

"If you're going to develop a vaccine you're going to have to do better than nature," he said.

So far, of course, researchers have not managed to do that.

Along with the 20,000-foot view that Fauci brings to the table, the Paris symposium will hear more about the basic science of HIV and its interaction with the immune system, which 30 years later, is still not completely understood, according to Barré-Sinoussi.

"We need to have some new discoveries in the field of immunology," she said. "There are still some missing pieces of the puzzle."

Barré-Sinoussi said she's also expecting to hear more about the so-called "functional cures" that made headlines earlier this year. In a functional cure, patients still remain infected, but they can control the virus without the aid of antiretroviral medications.

Exactly how that can be made to happen reliably remains an open question that -- if it could be answered -- would change the face of the HIV/AIDS pandemic.

She's looking forward to reports on the mechanisms by which HIV establishes itself in the body and then persists despite antiretroviral medications that prevent it from replicating.

And there will be more details at the symposium about vaccine research, including a debate on the best way to move forward after the partial success of a major trial 4 years ago and the recent failure of another.

What Barré-Sinoussi is not expecting is anything dramatic. An announcement of a breakthrough "would be wonderful, but I don't think we will have that."

On the other hand, no one immediately recognized the breakthrough by her and her colleagues 30 years ago, so time may tell.

Source

Co-infection with hepatitis B does not alter treatment response in chronic hepatitis C

Clin Res Hepatol Gastroenterol. 2013 May 9. pii: S2210-7401(13)00052-1. doi: 10.1016/j.clinre.2013.03.002. [Epub ahead of print]

Uyanikoglu A, Akyuz F, Baran B, Simsek BP, Ermis F, Demir K, Gulluoglu M, Badur S, Kaymakoglu S.

Harran University, Faculty of Medicine, Department of Gastroenterology, Sanliurfa, Turkey. Electronic address: auyanikoglu@hotmail.com.

Abstract

BACKGROUND/AIM: To investigate the clinical features and treatment response in patients with hepatitis B (HBV) and hepatitis C virus (HCV) co-infection receiving anti-HCV therapy.

PATIENTS AND METHOD: Patients with HBV/HCV co-infection, who were eligible for anti-HCV therapy, were included in the study. Patients had detectable HBsAg for at least 6months and detectable HCV-RNA before the initiation of therapy. Primary end-point was the proportion of patients achieving sustained virological response (SVR). HBV serology and HBV-DNA results obtained during the follow-up were assessed to determine HBV clearance or reactivation after anti-HCV therapy.

RESULTS: There were 612 patients in the HCV cohort and 52 (8.5%) of them were HBV/HCV co-infected. Twenty-eight patients (20 male, mean age: 47±12) received anti-HCV treatment and followed-up for a mean duration of 53months (12-156). Fifteen patients received peginterferon/ribavirin combination while the remaining patients received standard interferon/ribavirin combination (n=6) or standard interferon monotherapy (n=7). Patients receiving interferon monotherapy were under chronic hemodialysis therapy. SVR was achieved in 14 (50%) patients at the end of follow-up. The proportion of patients with SVR in three treatment arms were not significantly different (P=0.78). Eight of 11 patients with detectable HBV-DNA cleared HBV-DNA during treatment. Seven (25%) patients experienced a rebound in HBV-DNA, and one patient experienced an acute hepatitis flare which was controlled by tenofovir therapy. Two (7%) patients cleared HBsAg and one of them was seroconverted to anti-HBs.

CONCLUSION: Co-infection with HBV does not have a negative impact on the efficacy of anti-HCV treatment, but HBV-DNA should be monitored to overcome the risk of HBV exacerbation.

Copyright © 2013. Published by Elsevier Masson SAS.

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