News (Updated May 9, 2010)

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New HIV subtype found in Macao

2010-05-07

  MACAO , May 6 (Xinhua) -- The Health Bureau of Macao announced on Thursday that it has found a CRF12_BF subtype of HIV (human immunodeficiency virus) that is slightly different from the one found in other regions.

The new subtype was detected after the Bureau and the medical experts at the Chinese University of Hong Kong cooperated to carry out molecular biologic analysis of the HIV virus samples found in Macao between 2006 and 2007.

The Bureau said that unprotected sex was the major way through which the HIV was transmitted in Macao before 2004, but the number of needle-sharing drug abusers contracting HIV increased dramatically in that year, and the virus they contracted was the new HIV subtype.

The HIV can be divided into two strains, the HIV-1 and HIV-2, and CRF12_BF is a recombinant subtype of the virus, which has been found in South America and parts of Europe .

Being an international city, a large number of visitors flock into the city every day, which makes it unavoidable for foreign virus to be brought into Macao , the Bureau said.

The Bureau added that it has closely followed the situations of the patients who contracted the new HIV subtype, and they have reacted well to the medical treatment like other AIDS patients.

A total of six AIDS cases were recorded in the first quarter of this year, two of which were locals, bringing the total number of such cases to 433 since 1986 when the record was started.

To curb the spread of the deadly virus, the government of Macao Special Administrative Region (SAR) has formed a joint-department committee in 2005 to fight AIDS, and the SAR's anti-drug law was promulgated in 2009.

 

HIV Vaccine Secret Found in 'Elite Controllers'

Genetic Mutation Allows Some People to Never Get AIDS

By Daniel J. DeNoon
WebMD Health News

Reviewed by Laura J. Martin, MD

May 7, 2010 - Harvard/MIT researchers appear to have solved one of the great mysteries of HIV -- and may at last be on track to develop an effective AIDS vaccine.

The mystery is why about one in 200 people infected with HIV -- dubbed "elite controllers" -- never get AIDS. It's long been thought that solving this secret would lead to the Holy Grail of AIDS research: an effective vaccine.

Now researchers led by MIT's Arup Chakraborty, PhD, and Harvard's Bruce D. Walker, MD, report that elite controllers have a rare set of genes that allow their immune systems to unleash killer T cells with unusual powers. The findings come from an elegant series of experiments, including study of 1,100 elite controllers and 800 people with AIDS.

Normal killer T cells work as a team. It usually takes a swarm of these cells, which recognize different bits of a virus, to kill virus-infected cells. But this process is too slow to stop fast-mutating viruses such as HIV. The astonishing ability of HIV to change its spots via mutation is one reason the normal immune system can't control the virus.

The killer T cells in elite controllers don't need help. They knock off virus-infected cells all by themselves. Moreover, they are "broadly reactive" and can kill off mutant HIV variants as they arise.

There's a downside to having broadly reactive killer T cells: They don't always leave normal cells alone. This makes elite controllers more susceptible to autoimmune diseases.

But there's an upside, too. Elite controllers aren't just impervious to HIV. They're also protected against other fast-growing viruses such as hepatitis C virus.

As it turns out, normal people have a few of these "broadly reactive" killer T cells. A few may be all that are needed.

"We think they might be coaxed into action with the right vaccine," Chakraborty says in a news release.

Once activated and directed against HIV, these super killers would naturally expand by cloning themselves in large numbers.

The study drew praise from Nobel laureate and CalTech researcher David Baltimore, PhD.

"Rarely does one read a paper that stretches the mind so surprisingly far," Baltimore says in a news release.

Chakraborty, Walker, and colleagues report their findings in the May 5 online issue of the journal Nature.

 

Roche’s patent on HIV drug is dismissed

The Swiss drug maker has the option of filing an appeal against the patent office’s decision on Valcyte with IPAB

Radhieka Pandeya

New Delhi : People living with HIV may soon be able to buy cheaper versions of antiviral drug Valcyte, the oral dosage form of intravenously administered ganciclovir, which is used to treat HIV-related infections.

On Wednesday, the Indian Patent Office annulled the patent on Valcyte, granted to Swiss drug maker F. Hoffmann-La Roche Ltd, following opposition by domestic drug makers and patient groups.

Cipla Ltd, Ranbaxy Laboratories Ltd, Matrix Laboratories Ltd and Bakul Pharma Ltd, along with patient groups Indian Network for People Living with HIV/AIDS and Tamil Nadu Networking People with HIV/AIDS, had challenged the Valcyte patent on technical grounds.

“Since the object of the invention is to provide a prodrug of ganciclovir with improved oral bioavailability, the comparison provided in the specification to show such an improvement is not scientific,” said S.P. Subramaniyan, patent controller.

A prodrug is biologically inactive itself, but gets converted into an active drug inside the body. Bioavailability is the amount of a drug that reaches the systemic circulation in its original form after administration.

Amar Lulla, chief executive of Cipla, said the patent office’s decision was fair.

“We are exploring the legal options,” said a spokesperson for Roche.

In August, Roche reduced the price of Valcyte by nearly one-third after the government slashed import duty on it. The medicine became available for Rs475 per tablet, down from Rs700. But the generic version of Valcyte, launched by Cipla in 2008 under the brand name Valcept, costs Rs245 a tablet, or Rs64,680 for the entire treatment—almost half the cost of treatment with Valcyte.

Roche filed patent and trademark infringement lawsuits in the Bombay high court as Cipla’s version defied its patent. But with Roche’s patent now annulled, the lawsuits may also be dismissed. Cipla can continue selling its generic version, while other manufacturers can launch their own versions.

“If there is no patent, they (Roche) cannot fight anything,” said Anand Grover, director of the Lawyers Collective on HIV/AIDS in India , who was a counsel for the two patient groups opposing the patent.

However, Roche has the option of filing an appeal against the patent office’s decision at the Intellectual Property Appellate Board (IPAB).

“Since this appears a well- reasoned and logically coherent decision, the chances of it being overruled by IPAB are slim,” said Shamnad Basheer, professor in intellectual property law at National University of Juridical Sciences.

“This decision sends a strong signal to the world that India will not permit very obvious tweaking of existing molecules, but will permit only meritorious pharmaceutical inventions to pass the patentability filter,” he added.

radhieka.p@livemint.com

 

FDA probes risks of HIV, prostate, other drugs

Tue, May 4 2010

WASHINGTON (Reuters) - U.S. regulators are investigating potential risks from Abbott Laboratories Inc's HIV drug Kaletra, GlaxoSmithKline Plc's prostate drug Avodart and other medicines.

The Food and Drug Administration said on Monday it was probing reports of liver toxicity with patients who used Kaletra to prevent HIV infection after exposure to the AIDS virus.

The agency also said it was investigating cases of male breast cancer in patients treated with Avodart as well as Merck & Co's prostate drug Proscar and baldness treatment Propecia.

The FDA releases a quarterly list of safety probes to inform the public about early investigations of potential side effects that have been reported. The list released on Monday covered issues identified between October and December 2009.

Being on the list does not mean the FDA has concluded the drug causes the specific risk, the agency said.

Abbott spokeswoman Elizabeth Hoff said the company added information to Kaletra's label last week noting that patients who took the drug to prevent HIV infection were among those who should undergo liver monitoring tests.

The label says some reported cases of liver dysfunction were serious. "However, a definitive causal relationship with Kaletra therapy has not been established," the drug label says.

Merck spokeswoman Pam Eisele said the prescribing instructions for Proscar and Propecia already mention cases of male breast cancer seen in clinical trials. Both drugs contain the same active ingredient.

"A causal relationship has not been established," she said.

Glaxo spokeswoman Sarah Alspach said the company evaluates all reported cases of breast cancer in men taking Avodart.

"Based on reports evaluated to date, there is not conclusive evidence of a causal association between Avodart and male breast cancer," she said.

The FDA posted the list.

(Reporting by Lisa Richwine; Editing by Tim Dobbyn; Carol Bishopric)

 

Discovery Of Potential New Drug Target To Combat Kaposi's Sarcoma

08 May 2010   

Research from the University of Leeds has identified how the virus which causes Kaposi's Sarcoma replicates and spreads - opening a door to a possible new treatment for the disease.

Kaposi's Sarcoma is a cancer caused by a human herpes virus and is widespread in sub-Saharan Africa , where it is the most common cause of cancer amongst those infected with HIV.

Researchers from Leeds ' Faculty of Biological Sciences found that a human protein - known as PYM - is hijacked by the virus to help it replicate. A virus-encoded protein, ORF57, interacts with PYM and when this interaction was blocked during molecular experiments, the virus was unable to replicate. The findings are published in the EMBO Journal.

"This is the first time that the cellular protein, PYM, has been shown to play a role in virus replication and Kaposi's Sarcoma," explains Dr Adrian Whitehouse, who led the research. "Our work is still at a very early stage, but it should in time be possible to design drugs which block the interaction between PYM and the virus protein, thereby stopping the virus replicating and hopefully stopping the cancer from developing."

Kaposi's Sarcoma-associated herpesvirus is an opportunistic infection which is most prevalent amongst people with a weakened immune system, such as those infected with HIV. Treatment for KS does exist but currently involves chemotherapy and highly active antiretroviral therapy which is both toxic and not always effective. Moreover, such combined therapies are only available to a small percentage of those affected in sub-Saharan Africa and other parts of the developing world.

The researchers - funded by the Wellcome Trust and BBSRC - are now looking to obtain the structure of these two interacting proteins, as the next step towards designing an anti-viral drug to combat the disease.

Source:
Dr. Adrian Whitehouse
University of Leeds

 

Dynavax Completes Over 2000 First Immunizations In Phase 3 Study

07 May 2010   

Dynavax Technologies Corporation (NASDAQ: DVAX) reported completing the first immunizations of over 2,000 subjects enrolled in its large-scale Phase 3 study of HEPLISAV™. This starts a 12-month follow-up on these subjects and sets the study's completion for May 2011. Dynavax said this event supports its goal of a BLA submission for HEPLISAV in the second half of 2011.

About HEPLISAV

HEPLISAV is an investigational adult hepatitis B vaccine. The vaccine candidate is being evaluated in two Phase 3 studies that are directed toward fulfilling licensure requirements in U.S. , Canada and Europe . In a completed pivotal Phase 3 trial, HEPLISAV demonstrated increased, rapid protection with fewer doses than current licensed vaccines. Dynavax has worldwide commercial rights to HEPLISAV and is developing the vaccine for large, high-value populations that are less responsive to current licensed vaccines, including individuals with chronic kidney disease. HEPLISAV combines hepatitis B surface antigen with a proprietary Toll-like Receptor 9 agonist known as ISS to enhance the immune response.

About Hepatitis B Vaccines

Currently available hepatitis B vaccines require three doses over six months to achieve full immunogenicity in healthy patient populations. Because compliance with this vaccine regimen is low, new vaccines are needed to provide increased protection with fewer doses in a shorter timeframe. Furthermore, currently available vaccines do not fully address the needs of several patient populations, including those with chronic kidney disease, HIV or chronic liver disease. In particular, patients with compromised immune systems require both rapid and enhanced protection, either because they are less responsive to conventional vaccine regimens or because they are at high risk of infection.

Source
Dynavax Technologies Corporation

 

FDA Recommends New Dosing For Colcrys(R) (Colchicine, USP) When Co-Administered With Protease Inhibitors

07 May 2010   

URL Pharma, Inc., announced that the U.S. Food and Drug Administration (FDA) has issued new label information affecting all approved protease inhibitors for treatment of HIV when co-administered with Colcrys® (colchicine, USP). These dosing guidelines are intended to avoid potentially fatal drug-drug interactions.

These new dosing recommendations were issued as a result of several clinical studies designed and conducted by URL Pharma that uncovered the risk of serious interactions when colchicine is taken along with certain other prescription medications. In addition to protease inhibitors, the URL Pharma studies discovered potentially dangerous interactions between colchicine and certain hypertension medications and antibiotics. URL Pharma conducted 17 clinical trials as part of its submissions to the FDA in the 3 New Drug Applications (NDAs) filed for Colcrys.

"The drug-drug interaction studies we conducted for Colcrys have yielded new and critically important guidance for physicians on the safe and appropriate use of colchicine, particularly among special populations, and represent a significant public health milestone in the treatment of gout," said Matthew W. Davis, M.D., R.Ph., Chief Medical Officer. "Prior to our work, scientifically rigorous guidance on dosing colchicine to avoid drug interactions was virtually non-existent. We urge all healthcare providers to consult the new labeling for protease inhibitors prior to concomitant use with Colcrys."

New Colcrys Dosing Guidance

The new dosing adjustment covers all approved protease inhibitors for the treatment of HIV-1 infection, including Lexiva® (fosamprenavir calcium) and ritonavir.

-- Patients with hepatic or renal impairment: For the prevention or treatment of gout flares, or for FMF, FDA has recommended against the co-administration of Colcrys with protease inhibitors.

-- Acute gout flares: The new recommended dosing for the treatment of gout flares is 0.6 mg (1 tablet) x 1 dose, followed by 0.3 mg (half tablet) 1 hour later; this dose to be repeated no earlier than 3 days.

For patients taking Lexiva without ritonavir, the suggested dose is 1.2 mg (2 tablets) x 1 dose; this dose is to be repeated no earlier than 3 days.

-- Prophylaxis of Gout Flares: In patients taking Colcrys for the prophylaxis of gout flares, FDA recommends that if the original colchicine regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg once a day. If the original colchicine regimen was 0.6 mg once a day, the regimen should be adjusted to 0.3 mg once every other day.

In patients taking Lexiva without ritonavir, FDA recommends that if the original Colcrys regimen was 0.6 mg twice a day, the regimen should be adjusted to 0.3 mg twice a day or 0.6 mg once a day. However, if the original Colcrys regimen was 0.6 mg once a day, FDA recommends it be adjusted to 0.3 mg once a day.

-- Familial Mediterranean fever (FMF): In patients with FMF, FDA recommends a maximum daily dose of Colcrys of 0.6 mg (may be given as 0.3 mg twice a day) when co-administered with protease inhibitors.

However, in FMF patients taking Lexiva without ritonavir, the maximum daily dose of Colcrys is recommended to be no more than 1.2 mg (may be given as 0.6 mg twice a day).

"At URL Pharma, patient safety is our primary concern," said Richard H. Roberts, M.D., Ph.D., President, Chief Executive Officer and Chairman of URL Pharma. "This is evidenced by the fact that our rigorous clinical program for Colcrys discovered these previously unknown drug-drug interactions. Patients and physicians should feel confident that they are prescribing and using a thoroughly tested, FDA-approved medication that meets all modern standards of safety, efficacy, purity, consistency and labeling."

Colcrys received approval from the U.S. Food and Drug Administration (FDA) on July 30, 2009 for use in treating acute gout flares at the first sign of a flare, and for the treatment of FMF. Colcrys received FDA approval for the prophylaxis of gout flares on October 19, 2009. It is the first and only single-agent colchicine treatment to receive FDA approval.

About Gout and Painful Gout Flares

Gout is a painful form of arthritis that affects an estimated 3 to 5 million Americans, most commonly adult men. It occurs when excess uric acid in the body is deposited as needle-like crystals, or tophi, in the joints or soft tissues, which cause inflammatory arthritis and can lead to gout flares typically lasting three to 10 days.

Gout flares are characterized by intermittent swelling, redness, heat, joint stiffness and pain, which are often excruciating and can be debilitating enough to significantly interfere with work, social activities and daily living. For many people, gout initially affects the joint of the big toe, though it can also affect other joint areas such as the ankles, heels, knees, wrists, fingers and elbows.

Important Safety Information

COLCRYS (colchicine, USP) tablets are indicated for the treatment of acute gout flares.

COLCRYS is contraindicated in patients with renal or hepatic impairment who are concurrently prescribed P-gp inhibitors or strong inhibitors of CYP3A4 as life-threatening or fatal toxicity has been reported. Dose adjustments of COLCRYS may be required when co-administered with P-gp or CYP3A4 inhibitors. The most common adverse events in clinical trials for the prophylaxis and treatment of gout were diarrhea and pharyngolaryngeal pain. Rarely, myelosuppression, thrombocytopenia, and leukopenia have been reported in patients taking colchicine. Rhabdomyolysis has been occasionally observed, especially when colchicine is prescribed in combination with other drugs known to cause this effect. Monitoring is recommended for patients with a history of blood dyscrasias or rhabdomyolysis.

 


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