News (Updated March 1, 2009)

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New drugs needed to fight flu pandemic

Fri Feb 27, 2009 6:14am EST

By Tan Ee Lyn

HONG KONG (Reuters) - Experts on Friday urged governments on Friday to diversify their stockpiles of drugs and called for more new medicines to fight what could be the world's next flu pandemic caused by the H5N1 bird flu virus.

Many advanced countries stock up on oseltamivir and zanamivir, two varieties of the same class of drugs that stops the H5N1 virus from multiplying.

But oseltamivir has proven to be largely useless in fighting the H1N1 seasonal human influenza virus and experts are questioning how well, and how long, the drug would stand up against the H5N1 virus, should it unleash a pandemic.

"We have been extremely foolish on our policies of stockpiling drugs. We have been stockpiling two varieties of the same drug," virologist Robert Webster at the St Jude Children's Hospital in the United States said at a medical conference in Hong Kong .

He said the resistance of the H1N1 virus to oseltamivir was as high as 98 percent worldwide.

"The likely scenario is that the (H5N1) virus will become resistant when you start using more and more (of one) drug, you get resistant (H5N1) mutants," he told Reuters later.

The U.S. Centers for Disease Control and Prevention said in December 2008 that 49 out of 50 H1N1 virus samples tested were no longer sensitive to oseltamivir, which is made by Roche AG and Gilead Sciences Inc..

Relenza, known generically as zanamivir, is made by GlaxoSmithKline under license from Australia 's Biota Inc..

Viruses and bacteria are sturdy organisms that fight hard to survive and adapt swiftly to drugs that are used to kill them, quickly becoming resistant to them.

Experts at the conference said most H1N1 viruses were sensitive to oseltamivir just a few years ago but learnt to adapt to the drug very quickly.

They warned that H5N1 could learn to adapt quickly to oseltamivir, just as H1N1 has done, because both viruses share a similar "N1" protein component.

Scientists in Vietnam reported in the past how certain strains of H5N1 were no longer sensitive to oseltamivir, resulting in the deaths of several infected patients.

Experience with viruses similar to H5N1 suggests that it would best be tackled with a combination of drugs, Webster said.

"Studies with HIV, leukemia have shown that we have to use multiple drugs," he said. He suggested that oseltamivir and zanamivir be trialled alongside other drugs like ribavirin and the adamantane class of drugs, like amantadine and rimantadine.

Malik Peiris a microbiologist with the University of Hong Kong said: "There is a need for developing new antivirals (drugs). Some are in very early clinical trials but development should be stepped up so there is a diversification of options."

(Editing by Valerie Lee)

 

HIV mutates at high speed to avoid immune system: study

AFP - Thursday, February 26

PARIS (AFP) - - A worldwide team of scientists said the human immunodeficiency virus (HIV) was swiftly evolving to avoid the body's immune defences, a phenomenon that adds to the challenge of crafting an AIDS vaccine.

Mutations in HIV enable it to rapidly sidestep genetic variations that offer a better natural shield against the deadly pathogen, they said in a study released by the journal Nature.

"Even in the short time that HIV has been in the human population, it is doing an effective job of evading our best efforts at natural immune control of the virus," said Oxford University researcher Philip Goulder.

"This is high-speed evolution that we're seeing in the space of just a couple of decades."

Goulder's team analysed the genetic codes and viral strain of 2,800 infected people in North America, the Caribbean, Europe, sub-Saharan Africa, Australia and Japan.

Their big focus was on so-called human leukocyte antigen (HLA) genes.

These control specialised proteins whose job is to act as a signaller against intruders. The proteins present little pieces of HIV to the body's heavy armour, T cells, which then seek out the virus and kill it.

Since HIV was identified as the cause of AIDS, more than a quarter of a century ago, doctors have learnt that even though no-one appears to be naturally immune to the virus, people progress to the full-blown disease at different rates.

Without antiretroviral drugs, some individuals may develop AIDS as little as a year after infection, while others take as long as two decades.

The span depends largely on inherited luck, for there are variants of HLA genes that are far better at combatting HIV than others. A tiny difference in DNA can make a huge difference in holding back the virus.

Goulder's team came across some bad news.

They found that the virus is able to mutate when facing the more successful variants of these genes.

This "escape mutation" is then transmitted on to the viral progeny and then handed on to the human population when another person becomes infected.

"Where a favourable HLA gene is present at high levels in a given population, we see high levels of the mutation that enable HIV to resist this particular gene effect," said co-author Rodney Phillips in a press release issued by Oxford University.

"The virus is outrunning human variation, you might say."

The study adds a further complexity in the quest for an HIV vaccine, say the authors.

Vaccine engineers will have to wrestle with different "escape mutations" in HIV that exist in distinct pools of populations.

For instance, a highly favourable variant of HLA is called HLA-B*51. It is common among people in Japan -- and, as a result, two-thirds of infected people there have a strain of HIV which features the "escape mutation" for this variant.

In Britain and Africa, though, HLA-B*51 is far less common. As a result, only between 15 to 25 percent of HIV-infected people have the "escape mutation" in their version of the virus.

So it means that a successful HIV vaccine may have to take these geographical differences into account, as well as the stealthy, slippery mutability of the virus itself.

"The implication is that once we have found an effective vaccine, it would need to be changed on a frequent basis to catch up with the evolving virus, much like we do today with the flu vaccine," said Goulder.

AIDS first emerged in 1981 as a novel disease that destroys immune cells, exposing the body to opportunistic infections. HIV was identified as its source in 1983. Twenty-five million people have died of AIDS and an estimated 33 million people have HIV.

The new paper focuses only on HIV's ability to sidestep natural immune systems. It did not address the virus' mutability towards anti-HIV drugs.

 

Matrix Laboratories says gets WHO approval for HIV durg

Reuters - Thursday, February 26

MUMBAI, Feb 26 - Matrix Laboratories Ltd said it got approval from the World Health Organisation for generic version of a drug to treat the human immuno-deficiency virus .

The WHO approval enables Matrix to market Lopinavir or Ritonavir tablets in dosages of 200 mg or 50 mg in most countries outside the United States and Europe , the company said in a statement on Thursday.

The tablets are the generic version of Abott Laboratories' Kaltera tablets, it added.

 

Interruptions in HIV therapy common in ex-inmates

Tue Feb 24, 2009 4:20pm EST

NEW YORK (Reuters Health) - Results of a new study show that major interruptions in HIV drug treatment occur after release from prison.

Within 60 days of release from prison, just 30 percent of HIV-infected inmates in the Texas Department of Criminal Justice system filled a prescription for antiretroviral drug therapy, researchers report in Wednesday's issue of the Journal of the American Medical Association.

Moreover, 90 percent or more of inmates did not fill a prescription soon enough to avoid an interruption in their antiretroviral therapy, according to the report.

"These remarkably high rates of lengthy HIV treatment interruptions are troublesome from a public health perspective," study investigator Dr. Jacques Baillargeon, from the University of Texas Medical Branch , Galveston , noted in a written statement.

"Several studies suggest that many released inmates who discontinue antiretroviral therapy also resume high-risk behaviors such as injection drug use or unsafe sex," Baillargeon added, "and this combination may result not only in poor clinical outcomes for these individuals but also in the creation of drug-resistant HIV reservoirs in the general community."

The study involved 2115 HIV-infected inmates who were receiving antiretroviral therapy prior to their release from prison between January 2004 and December 2007.

Just 5.4 percent of inmates filled an antiretroviral prescription within 10 days of release, the researchers found.

Hispanic and African American inmates were 60 percent less likely than white inmates to fill a prescription within 10 days, and 30 percent less likely to do so within 30 days.

"Adequately addressing a public health crisis of this scale and complexity will require carefully coordinated efforts between academic institutions, the criminal justice system, and public health agencies," the researchers conclude.

SOURCE: Journal of the American Medical Association, February 25, 2009.

 

Mylan says WHO approves heat-resistant HIV drug

Wednesday February 25, 2009, 2:38 pm EST

NEW YORK (AP) -- The World Health Organization approved an HIV drug designed to withstand heat in warm climates, Mylan Inc. said Wednesday

Mylan said the WHO's prequalification program approved a generic version of Abbott Laboratories' drug Kaletra, which is sold in the developing world as Aluvia. The drug is designed to be heat-stable and low-cost, making it more practical to distribute and use in countries with warm climates. The approval clears the way for marketing the drug in many countries outside the U.S. and Europe .

The generic tablet combines the drugs lopinavair and ritonavir. It is being made by Matrix Laboratories Ltd. of India . Pittsburgh-based Mylan owns a 71.5 percent stake in Matrix.

Abbott reported $378 million in Kaletra revenue in 2008.

 



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