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From: nataphcvhiv@...
To: hiv@..., nataphcvhiv@..., natapindustry@..., natapdoctors@...
Sent: 4/30/2009 4:25:44 A.M. Central Daylight Time
Subj: NATAP: Resistance Risk with Flu Drugs

 

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'High Risk' of Resistant Swine Flu, Researcher Says

By Todd Neale, Staff Writer, MedPage Today Published: April 29, 2009

CANNES, France, April 29 -- Using single antiviral drugs to treat the current outbreak of swine influenza could result in the development of a resistant strain, a leading flu researcher said here. The H1N1 virus currently infecting humans around the globe is already resistant to one of the two classes of antiviral medications, the adamantanes (rimantadine and amantadine). The virus is, however, susceptible to the neuraminadase inhibitors, oseltamivir (Tamiflu) and zanamivir (Relenza). The risk is high that a strain resistant to all of these drugs could develop as long as the disease continues to be treated with single medications, Robert Webster, Ph.D., of St. Jude Children's Research Hospital in Memphis, said at the conference on Influenza Vaccines for the World. "We can't continue to use single antiviral drugs. . . . The virus will win the game," he said. He said he couldn't guess how long it would take for resistance to occur, "but if you use a mono drug you will get resistance." The increased risk is compounded by the background resistance that develops spontaneously by mutation, he said. For example, up to 67% of seasonal H1N1 influenzas in Norway were resistant to oseltamivir during the 2007-2008 flu season, according to Jennifer McKimm-Breschkin of CSIRO Molecular & Health Technologies in Australia. This occurred even though Norwegian doctors made very little use of oseltamivir, illustrating the ability of resistance to develop without any drug treatment. More drug exposure might enable these resistant viruses to become the predominant strain more rapidly, she said. She noted that during the following winter in the southern hemisphere, oseltamivir-resistance reached a prevalence of 93% in Australia and 100% in South Africa. Dr. Webster suggested that drug combinations would be the best strategy for avoiding this problem, a lesson learned, he said, from HIV. "We know all the ground rules. With an RNA virus you need two, three, or four drugs in combination," he said. But, he noted, "we haven't got them yet for flu. . . . That's the bottom line." In his laboratory, adding ribavirin to the neuraminadase inhibitors has yielded some additional benefit, but ribavirin is not approved for use against flu. Other drugs, such as monoclonal antibodies and immune system modulators, might also be used in combination to help control the immune response to infection, he said. But until some of these combinations are proven and approved for use, he said treatment of potential pandemic flu viruses, including the swine flu, would have to continue with the single antivirals. "At the moment, we don't have an option," he said. Dr. McKimm-Breschkin noted that regulatory authorities and the health community now recommend a diversified antiviral stockpile of oseltamivir and zanamivir, which she said would attenuate the risk of resistance. Tests Outline Swine Flu Resistance Pattern Download Complimentary Source PDF By Michael Smith, North American Correspondent, MedPage Today Published: April 29, 2009 Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco Earn CME/CE credit for reading medical news TORONTO, April 29 -- The swine flu virus contains a combination of gene segments that had not been previously reported in either swine or human influenza viruses, the CDC said. Action Points   Explain to interested patients that analysis of the emerging swine flu has revealed a previously unknown viral structure. Note that one aspect of the analysis is the resistance pattern of the new virus -- it is resistant to one of the two classes of antiviral drugs. But among the findings when the agency tested virus isolates was a mutation known to confer resistance to the adamantane class of anti-flu drugs, the agency said in aMorbidity and Mortality Weekly Report dispatch. The so-called S31N mutation in the M2 protein confers cross-resistance to amantadine (Symmetrel) and rimantadine (Flumadine), the agency said, and was found in all 13 of the tested isolates. In addition, a partial sequence of the swine flu M gene revealed changes characteristic of the emerging virus, the agency said. On the other hand, all of the isolates were susceptible to members of the other class of anti-flu drugs, the neuraminidase inhibitors, the agency found. So far, resistance testing has been carried out on isolates from 20% of the 64 laboratory-confirmed cases of swine flu. Adamantane susceptibility was assessed by conventional sequencing or pyrosequencing, using viral RNA. Susceptibility to the neuraminidase inhibitors was tested by a commercially available chemiluminescent neuraminidase inhibition assay. Four neuraminidase inhibitors were tested -- oseltamivir (Tamiflu), zanamivir (Relenza), peramivir, and A-315675 -- although the latter two are not yet approved in the U.S. For the test viruses, the drug concentration needed to inhibit 50% of neuraminidase enzyme activity -- the so-called IC50 -- was compared to the IC50 of A/Georgia/17/2006, an H1N1 seasonal virus sensitive to the drugs. All the samples exhibited values similar to the control virus, the agency found. The agency also tested for H274Y -- the most commonly detected mutation in oseltamivir-resistant viruses -- and did not find it in any of the samples. Only two classes of antiviral drugs are approved by the FDA for use in treating or preventing influenza infections -- the adamantanes or M2 blockers and the neuraminidase inhibitors. The adamantanes are effective against influenza A viruses -- although not all, since the swine flu is an A virus -- but not influenza B viruses, which lack the M2 protein. Because of growing resistance, the CDC has not recommended their use since 2005, although the emergence of resistance to oseltamivir in seasonal influenza viruses this season led to changes in recommendations. (See Resistance to Oseltamivir (Tamiflu) Grows Higher) In contrast, until this flu season, the neuraminidase inhibitors had previously had a lower frequency of antiviral resistance during therapeutic use, the agency said. Primary source: Morbidity and Mortality Weekly Report Source reference: Centers for Disease Control "Update: Drug susceptibility of swine-origin Influenza A (H1N1) viruses, April 2009" MMWR 2009; 58: 1-3.

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From: nataphcvhiv@...
To: hiv@..., nataphcvhiv@..., natapindustry@..., natapdoctors@...
Sent: 4/30/2009 4:16:35 A.M. Central Daylight Time
Subj: NATAP: "Flu is Mild" Scientists say

 

NATAP http://natap.org/
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Scientists see this flu strain as relatively mild

Genetic data indicate this outbreak won't be as deadly as that of 1918, or even the average winter.

By Karen Kaplan and Alan Zarembo latimes.com
April 30, 2009

As the World Health Organization raised its infectious disease alert level Wednesday and health officials confirmed the first death linked to swine flu inside U.S. borders, scientists studying the virus are coming to the consensus that this hybrid strain of influenza -- at least in its current form -- isn't shaping up to be as fatal as the strains that caused some previous pandemics.

In fact, the current outbreak of the H1N1 virus, which emerged in San Diego and southern Mexico late last month, may not even do as much damage as the run-of-the-mill flu outbreaks that occur each winter without much fanfare.

 

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"Let's not lose track of the fact that the normal seasonal influenza is a huge public health problem that kills tens of thousands of people in the U.S. alone and hundreds of thousands around the world," said Dr. Christopher Olsen, a molecular virologist who studies swine flu at the University of Wisconsin School of Veterinary Medicine in Madison.

His remarks Wednesday came the same day Texas authorities announced that a nearly 2-year-old boy with the virus had died in a Houston hospital Monday.

"Any time someone dies, it's heartbreaking for their families and friends," Olsen said. "But we do need to keep this in perspective."

Flu viruses are known to be notoriously unpredictable, and this strain could mutate at any point -- becoming either more benign or dangerously severe. But mounting preliminary evidence from genetics labs, epidemiology models and simple mathematics suggests that the worst-case scenarios are likely to be avoided in the current outbreak.

"This virus doesn't have anywhere near the capacity to kill like the 1918 virus," which claimed an estimated 50 million victims worldwide, said Richard Webby, a leading influenza virologist at St. Jude Children's Research Hospital in Memphis, Tenn.

When the current virus was first identified, the similarities between it and the 1918 flu seemed ominous.

Both arose in the spring at the tail end of the flu season. Both seemed to strike people who were young and healthy instead of the elderly and infants. Both were H1N1 strains, so called because they had the same types of two key proteins that are largely responsible for a virus' ability to infect and spread.

The Centers for Disease Control and Prevention and the National Institutes of Health published genetic sequence data Monday morning of flu samples isolated from patients in California and Texas, and thousands of scientists immediately began downloading the information. Comparisons to known killers -- such as the 1918 strain and the highly lethal H5N1 avian virus -- have since provided welcome news.

"There are certain characteristics, molecular signatures, which this virus lacks," said Peter Palese, a microbiologist and influenza expert at Mt. Sinai Medical Center in New York. In particular, the swine flu lacks an amino acid that appears to increase the number of virus particles in the lungs and make the disease more deadly.

Scientists have identified several other differences between the current virus and its 1918 predecessor, but the significance of those differences is still unclear, said Dr. Scott Layne, an epidemiologist at the UCLA School of Public Health.

Ralph Tripp, an influenza expert at the University of Georgia, said that his early analysis of the virus' protein-making instructions suggested that people exposed to the 1957 flu pandemic -- which killed up to 2 million people worldwide -- may have some immunity to the new strain.

That could explain why older people have been spared in Mexico, where the swine flu has been most deadly.

The swine virus does appear able to spread easily among humans, which persuaded the WHO to boost its influenza pandemic alert level to phase 5, indicating that a worldwide outbreak of infection is very likely. And the CDC reported on its website that "a pattern of more severe illness associated with the virus may be emerging in the United States."

"We expect to see more cases, more hospitalizations, and, unfortunately, we are likely to see more deaths from the outbreak," Health and Human Services Secretary Kathleen Sebelius told reporters Wednesday on her first day at work.

But certainly nothing that would dwarf a typical flu season. In the U.S., between 5% and 20% of the population becomes ill and 36,000 people die -- a mortality rate of between 0.24% and 0.96%.

Dirk Brockmann, a professor of engineering and applied mathematics at Northwestern University in Evanston, Ill., used a computer model of human travel patterns to predict how this swine flu virus would spread in the worst-case scenario, in which nothing is done to contain the disease.

After four weeks, almost 1,700 people in the U.S. would have symptoms, including 198 in Los Angeles, according to his model. That's just a fraction of the county's thousands of yearly flu victims.

Just because the virus is being identified in a growing number of places -- including Austria, Canada, Germany, Israel, New Zealand, Spain and Britain -- doesn't mean it's spreading particularly quickly, Olsen said.

"You don't ever find anything that you don't look for," he said. "Now that diagnostic laboratories and physicians and other healthcare workers know to look for it, perhaps it's not surprising that you're going to see additional cases identified."

And a pandemic doesn't necessarily have a high fatality rate. Even in Mexico, the fatalities may simply reflect that hundreds of thousands of people have been infected. Since the symptoms of swine flu are identical to those of a normal flu, there's no way to know how many cases have evaded government health officials, St. Jude's Webby said.

As the virus adapts to its human hosts, it is likely to find ways of spreading more efficiently. But evolution also suggests it might become less dangerous, Olsen said.

"If it kills off all its potential hosts, you reach a point where the virus can't survive," he said. Working to calm public fears, U.S. officials on Wednesday repeatedly stressed the statistic of yearly flu deaths -- 36,000.

Sebelius and Homeland Security Secretary Janet Napolitano also rejected calls to close the borders, which several lawmakers reiterated Wednesday on Capitol Hill.

"We are making all of our decisions based on the science and the epidemiology," Napolitano said. "The CDC, the public health community and the World Health Organization all have said that closing out nation's borders is not merited here."

Though scientists have begun to relax about the initial toll, they're considerably less comfortable when taking into account the fall flu season. They remain haunted by the experience of 1918, when the relatively mild first wave of flu was followed several months later by a more aggressive wave.

The longer the virus survives, the more chances it has to mutate into a deadlier form.

"If this virus keep going through our summer," Palese said, "I would be very concerned."

karen.kaplan@...

alan.zarembo@...

Staff writers Noam Levey in Washington, Thomas H. Maugh II in Los Angeles and Ken Ellingwood in Mexico City contributed to this report.

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Crowley addresses AIDS activists

NEWS

Published 04/30/2009

by Bob Roehr

	Jeff Crowley, center, speaks to AIDS advocates Monday during a forum that was part of the AIDS Watch congressional lobby days. Photo: Bob Roehr

President Obama's openly gay domestic AIDS policy chief addressed participants of the annual AIDS Watch congressional lobbying days Monday, and outlined his priorities.

During a public forum hosted by the National Association of People With AIDS, Jeff Crowley, the director of the Office of National AIDS Policy, said his office has been integrated into the White House domestic policy council. His three priorities are to develop a national HIV strategic plan, participate in the health reform debate, and focus on prevention.

Crowley, 43, at one point worked for NAPWA.

His office has $1.4 million to develop a national AIDS strategy and will be adding three to four staff people. Rather than push to do it within the first 100 days of the administration, Crowley thought it more important that "we need to do this right, we need to take our time."

Engaging other parts of the administration in writing the plan helps get them to buy into it and "also to hold them accountable" for its implementation, Crowley said. He cautioned the audience that they are developing a national strategy, and that may look different from a community HIV strategy.

"We need to think about how we get to health reform," said Crowley. Medicare and Medicaid are the largest payers of HIV care, while the Ryan White CARE Act programs are meant to fill in the gaps and special needs. He believes it makes sense to defer significant revisions in the Ryan White programs until the outline of health reform becomes clearer.

"We have a window of opportunity with HIV prevention," he said. "You are going to see more money" for it in the president's budget, but "it is not just about the money, it is about focusing what we are doing on prevention."

Crowley said they are "looking for a model [in all program activity] that will hold the federal government accountable" while at the same time promoting state and local responsibility and contributions to those efforts.

Earlier Monday, a crowd chanted, "We're watching and tired of waiting," during a rally to kick off AIDS Watch. The rally was at Freedom Plaza, the vast expanse of granite on Pennsylvania Avenue between the Capitol and the White House, and the temperature matched the rhetoric, unseasonably in the 9 0s.

Larry Bryant, with DC Fights Back, said the country had declared a state of emergency over a few dozen cases of swine flu while every nine and a half minutes someone in the United States is infected with HIV. If swine flu is an emergency, then HIV "is a Holocaust for my people," Bryant said.

Kathleen Sengstock, a member of Representative Maxine Waters's (D-California) staff, said the congresswoman is pushing three pieces of legislation to address the HIV/AIDS crisis. The Stop AIDS in Prisons Act has already passed the House. Waters also wants to see funding for the Minority AIDS Initiative increase from about $400 million to $610 million.

Waters also is about to reintroduce a bill that would require insurance companies to include routine screening for HIV as part of their regu lar coverage. An estimated 20 percent of people who are infected with the virus do not know that, and increased screening would both improve their health and rein in spread of new infections.

The Medicaid program will only cover the cost of an HIV test if the person is considered at risk for the infection, an administrative barrier that physicians say impedes making screening part of routine care.

Sengstock said there are jurisdictional reasons why Waters did not include Medicaid in her legislation, but the congresswoman is trying other means to resolve the issue.

Another priority for AIDS advocates is passage of the Early Treatment for HIV Act. Currently under Medicare and Medicaid rules one must have an AIDS-de fining illness in order to qualify for the program. The goal is to s upport earlier access to drugs according to current treatment guidelines.

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