Wednesday, January 30, 2008

Tamiflu effectiveness weakening rapidly

Revival for Relenza? So much for all those millions of doses that our wise governments have stockpiled. The money would have been better spent on research and on emergency manufacturing facilities

Roche Holding AG's Tamiflu may be losing potency against seasonal influenza in Europe after tests showed resistance to the drug in more than one of 10 samples. Tests on 148 virus specimens from patients with the H1N1 flu strain in 10 European countries found 19 that harbored resistance to the pill, most of them in Norway, the European Centre for Disease Prevention and Control said today.

The results show viruses capable of evading Tamiflu, also known as oseltamivir, may be spreading. Some resistant viruses were also found in the U.S., leading doctors to consider GlaxoSmithKline Plc's Relenza and other treatments for a disease the World Health Organization estimates causes 250,000 to 500,000 deaths globally each year. ``These preliminary results are in contrast to previous years where little or no resistance to oseltamivir was observed,'' Martina Rupp, a Roche spokeswoman, said in an e-mail today. More surveillance is needed to establish the prevalence and geographical distribution of the resistant H1N1 variants and to assess the impact on Tamiflu's effectiveness, she said. Basel, Switzerland-based Roche has ``informed health authorities worldwide about this situation,'' Rupp said. Roche fell 1.8 Swiss francs, or 0.9 percent, to 192.2 francs in Zurich trading. The shares have dropped 1.7 percent this year.

The H1N1 viruses identified in Europe that aren't susceptible to Tamiflu carry a so-called H274Y gene mutation that confers ``high-level resistance,'' said Frederick Hayden, a researcher with the WHO's Global Influenza Program in Geneva. Preliminary data from the U.S. Centers for Disease Control and Prevention in Atlanta ``indicate that there have been some of these kinds of resistant variants detected, albeit at low frequency, in the U.S.,'' Hayden said. Teleconferences will be held this week to gauge their geographic distribution, he said. Of 204 viral samples tested by the CDC during the 2007-2008 flu season, six, or 2.9 percent, were resistant to Tamiflu.

All those resistant samples were among 109 H1N1 viruses, for a rate of 5.5 percent in that strain, said Joseph Bresee, chief of the epidemiology and prevention branch of CDC's influenza division in Atlanta. ``It bears watching,'' he said today in a telephone interview. ``Our recommendations for use of oseltamivir haven't changed, but we're going to continue to do close monitoring on flu viruses from here on out.'' There's no evidence the mutation is associated with increased transmissibility or increased likelihood of causing disease, Hayden at the WHO said by telephone from Geneva today. ``This is an unexpected circumstance to see the circulation of H1N1 viruses harboring this particular mutation,'' he said.

Relenza and amantadine, an older class of antiviral medicine, are capable of fighting the mutant variant, health officials said. However, large numbers of flu viruses have other mutations that make them resistant to amantadine and a related drug, called rimantadine, Bresee said. Neither drug is recommended for treatment of seasonal flu in the U.S.

A WHO report last April said 2.2 percent of H1N1 samples from Japan, the world's biggest user of Tamiflu, had the H274Y mutation. There have been no reports from Japan of recent cases. The samples tested in Europe were taken from patients who hadn't been treated with Tamiflu, and resistance rates varied from country to country, Hayden said.

In Norway, 12 of 16 H1N1 samples taken from patients across the country this winter showed ``a high degree of resistance,'' the Norwegian Institute of Public Health said in a Jan. 25 statement. An H1N1 variant from the Solomon Islands is the dominant flu strain now circulating in the Scandinavian country and other parts of Europe, the Oslo-based institute said.

``It is disturbing that resistant viruses are now being detected in Europe, which has a very low level'' of antiviral use, said Jennifer McKimm-Breschkin, a virologist at the Commonwealth Science and Industrial Research Organization in Melbourne. ``This suggests that resistant viruses have obtained a growth advantage elsewhere on the globe, and have been sufficiently fit to now start spreading possibly globally even in the absence of widespread drug use.''

Tamiflu, which generated 2.63 billion francs ($2.4 billion) in sales for Roche in 2006, is the company's fourth-best-selling drug. Relenza, an inhaled medicine, had sales of 91 million pounds ($180 million) in the same year for London-based Glaxo. The medicines are being stockpiled by the Geneva-based WHO and governments around the world for use in the event of a pandemic, and to treat the H5N1 avian flu strain that's spread to more than 60 countries, infecting people in 14 of them.

``With the global focus on oseltamivir as the drug of choice for treating influenza, many clinicians are not even aware that there is an effective alternative: Relenza,'' McKimm-Breschkin said in a telephone interview today. Relenza and Tamiflu work by blocking neuraminidase -- one of the two surface proteins in influenza viruses and the ``N'' in H5N1 and H1N1 -- that allows the virus to spread from infected cells to other cells in the body.

The H5N1 bird flu strain could trigger a global outbreak if it adopts some of the characteristics of seasonal flu that enable it to be spread easily through coughing and sneezing. Seasonal flu strains with resistance to Tamiflu and other so-called neuraminidase inhibitors could potentially exchange genes with the pandemic strain, making the medicines a weaker weapon to fight the global contagion. ``Antiviral resistance to neuraminidase inhibitors has been clinically negligible so far, but is likely to be detected during widespread use during a pandemic,'' the WHO says on its Web site.


New AIDS drug

A new class of drug for people with HIV is being introduced in Britain today, having been described by researchers as a huge step forward in treating the deadly infection. Raltegravir, available as tablets to be taken twice a day, is approved for use with other antiretroviral drugs to treat HIV in about one in ten patients whose therapy has stopped working. Because of their potential to prolong life by decades, HIV drugs are considered cost-effective and raltegravir is likely to be available on the NHS for all infected patients.

Doctors believe that the drug could become standard treatment, potentially preventing HIV progressing into full-blown Aids. Three quarters of trial patients showed a significant reduction in viral load - the prevalance of the virus in their bloodstream - compared with 40 per cent taking current medication alone. Some patients had a marked improvement to the point where levels of the virus were "undetectable", doctors said.

An estimated 73,000 people in Britain are infected with HIV, or human immunodeficiency virus, which culminates in Aids (acquired immunodeficiency syndrome). Although HIV infection is still considered serious, early diagnosis and appropriate treatment can allow for a relatively normal lifespan.

HIV continually changes and can become resistant to treatment, leading to a continuing search for new drugs. Raltegravir is the first in a new class of HIV treatments called integrase inhibitors, which it is hoped will avoid the risks of heart attack and cancer associated with existing medication. It works by blocking integrase, an enzyme that HIV relies on to replicate itself. It affects the ability of the virus to infect other cells, thus reducing the blood's viral load.

During the trials, patients were given raltegravir or the dummy drug plus optimised background therapy (OBT), a regime of antiretroviral drugs tailored to individual patients.

One study published in The Lancet in April last year was based on 178 patients with advanced HIV. They had been taking regular antiretroviral drugs for about ten years but were not responding to them. Patients taking raltegravir had an average of a 98 per cent drop in their HIV ribonucleic acid (RNA) count, compared with 45 per cent in the dummy group. The number of CD4 cells, an indicator of the immune system's ability to fight disease, was also boosted.

Made by the US-based company Merck, the drug is also known by the brand name Isentress. Mark Nelson, director of HIV services at the Chelsea and Westminster Hospital, London, said that it had already provided a life-line to 30 of his patients. "While this is not a `cure' for HIV it does mean we can suppress the virus to where it is virtually undetectable."

Dr Nelson added that the drug's long-term safety record would be very important, given that more adverse effects from existing treatments were emerging after many years of therapy.

"Raltegravir is going to be popular because it's very effective and it seems to have a good safety profile," he said. "Previous drugs have done a terrific job keeping people alive. But now we have to start thinking about safety."

Eight years and four different drug cocktails after Philippe B, 41, learnt that he had HIV, he almost gave up.

"Ten years ago nobody told you anything about the drugs or how to take them, so I stopped for a few months. I became resistant and had to change my combination. Every new combination meant new side effects - nausea, diarrhoea. Sometimes the fatigue was so bad, I couldn't get out of bed."

Philippe, who works for the Terence Higgins Trust, had a viral load of 500,000 (more than 100,000 is considered high) and was in hospital with toxoplasmosis, ulcers and paralysis. After three months, he started a new regime that was the first to work - his viral load is below 50.

Philippe says that he is lucky because he has yet to run out of drug options. "It's very important that there are new drugs. HIV is not a death sentence any more but there's still no cure. After you become resistant, you start running out of options."



Just some problems with the "Obesity" war:

1). It tries to impose behavior change on everybody -- when most of those targeted are not obese and hence have no reason to change their behaviour. It is a form of punishing the innocent and the guilty alike. (It is also typical of Leftist thinking: Scorning the individual and capable of dealing with large groups only).

2). The longevity research all leads to the conclusion that it is people of MIDDLING weight who live longest -- not slim people. So the "epidemic" of obesity is in fact largely an "epidemic" of living longer.

3). It is total calorie intake that makes you fat -- not where you get your calories. Policies that attack only the source of the calories (e.g. "junk food") without addressing total calorie intake are hence pissing into the wind. People involuntarily deprived of their preferred calorie intake from one source are highly likely to seek and find their calories elsewhere.

4). So-called junk food is perfectly nutritious. A big Mac meal comprises meat, bread, salad and potatoes -- which is a mainstream Western diet. If that is bad then we are all in big trouble.

5). Food warriors demonize salt and fat. But we need a daily salt intake to counter salt-loss through perspiration and the research shows that people on salt-restricted diets die SOONER. And Eskimos eat huge amounts of fat with no apparent ill-effects. And the average home-cooked roast dinner has LOTS of fat. Will we ban roast dinners?

6). The foods restricted are often no more calorific than those permitted -- such as milk and fruit-juice drinks.

7). Tendency to weight is mostly genetic and is therefore not readily susceptible to voluntary behaviour change.

8). And when are we going to ban cheese? Cheese is a concentrated calorie bomb and has lots of that wicked animal fat in it too. Wouldn't we all be better off without it? And what about butter and margarine? They are just about pure fat. Surely they should be treated as contraband in kids' lunchboxes! [/sarcasm].

9). And how odd it is that we never hear of the huge American study which showed that women who eat lots of veggies have an INCREASED risk of stomach cancer? So the official recommendation to eat five lots of veggies every day might just be creating lots of cancer for the future! It's as plausible (i.e. not very) as all the other dietary "wisdom" we read about fat etc.

10). And will "this generation of Western children be the first in history to lead shorter lives than their parents did"? This is another anti-fat scare that emanates from a much-cited editorial in a prominent medical journal that said so. Yet this editorial offered no statistical basis for its opinion -- an opinion that flies directly in the face of the available evidence.

Even statistical correlations far stronger than anything found in medical research may disappear if more data is used. A remarkable example from Sociology:
"The modern literature on hate crimes began with a remarkable 1933 book by Arthur Raper titled The Tragedy of Lynching. Raper assembled data on the number of lynchings each year in the South and on the price of an acre's yield of cotton. He calculated the correlation coefficient between the two series at -0.532. In other words, when the economy was doing well, the number of lynchings was lower.... In 2001, Donald Green, Laurence McFalls, and Jennifer Smith published a paper that demolished the alleged connection between economic conditions and lynchings in Raper's data. Raper had the misfortune of stopping his analysis in 1929. After the Great Depression hit, the price of cotton plummeted and economic conditions deteriorated, yet lynchings continued to fall. The correlation disappeared altogether when more years of data were added."
So we must be sure to base our conclusions on ALL the data. But in medical research, data selectivity and the "overlooking" of discordant research findings is epidemic.

"What we should be doing is monitoring children from birth so we can detect any deviations from the norm at an early stage and action can be taken". Who said that? Joe Stalin? Adolf Hitler? Orwell's "Big Brother"? The Spanish Inquisition? Generalissimo Francisco Franco Bahamonde? None of those. It was Dr Colin Waine, chairman of Britain's National Obesity Forum. What a fine fellow!


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