Progress, no big breakthrough, in hunt for HIV cure

[ichigo_kun]

Progress, no big breakthrough, in hunt for HIV cure
By Deena Beasley
Sun Mar 11, 2012 9:05am EDT
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By Deena Beasley

(Reuters) - Scientists, stymied for decades by the complexity of the human immunodeficiency virus, are making progress on several fronts in the search for a cure for HIV infections, a leading medical research conference was told this week in Seattle.

Promising tactics range from flushing hidden HIV from cells to changing out a person's own immune system cells, making them resistant to HIV and then putting them back into the patient's body.

A major stumbling block is the fact that HIV lies low in pools or reservoirs of latent infection that even powerful drugs cannot reach, scientists told the Conference on Retroviruses and Opportunistic Infections, one of the world's largest scientific meetings on HIV/AIDS.

"We need to get the virus to come out of the latent state, then rely on the immune system or some other treatment to kill the virus," said Dr. Kevin De Cock, director of the Center for Global Health at the U.S. Centers for Disease Control and Prevention.

HIV, which surfaced more than 30 years ago, infects more than 33 million people worldwide. Thanks to prevention measures, tests that detect HIV early and new antiretroviral drugs that can control the virus for decades, infection with the virus that causes AIDS is no longer a death sentence.

Still, questions of cost, side effects, drug resistance and ultimate lifespan, make lifelong use of antiviral drugs a less-than-ideal solution.

The International AIDS Society last year formally added the aim of finding a cure to its HIV strategy of prevention, treatment and care.

Early human trials of vaccines designed to prevent or treat infection with the difficult to target virus have proved disappointing. HIV is a "provirus" that is integrated into the DNA of a host cell, where it can remain latent or eventually reactivate.

"It has proven to be an incredibly formidable challenge to develop a vaccine," said John Coffin, professor of molecular biology at Tufts University in Boston. "In recent years the pendulum is swinging back."

Scientific advances in molecular engineering are allowing researchers to delve more deeply into the mechanism of HIV.

"Vaccines work by recognizing the surface of the virus and eliminating it," said Dr. Dennis Burton, professor of immunology and microbial science at the Scripps Research Institute in La Jolla, California. "HIV is a highly evolved virus that has developed a surface incorporating features to avoid antibody responses," including instability.

He presented research showing that "broadly neutralizing antibodies" can be designed to recognize and penetrate HIV, giving researchers new vaccine targets.

Merck & Co presented data showing for the first time that its cancer drug Zolinza, also known as vorinostat, can disrupt latent HIV infection.

"Once you have a validated approach you can really go back to the drawing board in the labs and design molecules more suited to therapy," said Daria Hazuda, vice president for infectious disease discovery at Merck.

She said the company is currently exploring how to design future studies.

"The sobering fact is that only one competent provirus in one tissue could reseed the entire infection," said Dr. John Mellors, chief of the infectious disease division at the University of Pittsburgh.

Phillip Gregory, chief scientific officer at Sangamo BioSciences, said he was not "fanatically optimistic about priming the immune system to fight HIV" with a preventive vaccine.

He explained that because HIV is a "reverse transcriptase" virus it is constantly mutating, making it very difficult for the body's immune system to keep up. Vaccines induce the production of antibodies that recognize and bind to very specific viral surface molecules, but the HIV molecules end up with a variety of subtle molecular differences on their surface.

"Eradication is a very tough theoretical sell," he said. "What's going to work is getting to the point that we could reasonably expect the immune system to get it totally under control."

Sangamo is conducting two mid-stage trials of its gene therapy in which infection-fighting white blood cells known as CD4 cells are removed, manipulated to knock out the CCR5 gene used by HIV to infect cells and then replaced.

"The change is permanent. Those cells and their progeny will go on to carry that genetic change," said Geoffrey Nichol, head of research and development at Sangamo.

An earlier study of a single infusion of the gene therapy in six HIV-infected patients showed mixed results, eliminating the virus in one patient with a naturally occurring gene mutation.

In the newer trials, according to Sangamo, patients will first be treated with an agent that reduces the number of lymphocytes in the bone marrow. The aim is to prime the immune system to take up more of the genetically modified CD4 cells when they are returned to the patient.

(Reporting By Deena Beasley; Editing by Gary Hill)

http://mobile.reuters.com/article/idUSBRE82A05R20120311?irpc=932

[Dr.Strangelove]

An earlier study of a single infusion of the gene therapy in six HIV-infected patients showed mixed results, eliminating the virus in one patient with a naturally occurring gene mutation.

This is somewhat imprecise. Sangamo doesn't seem to say much about the actual numbers but from what I understood from their press release the vial load was reduced in all patients but only one patient went actually undetectable.
That doesn't mean that the virus was 'eliminated' though. I doubt he will stay undetectable without constant new infustions of his modified CD4 cells.

[newt]

Vorinostat, as proof of concept and even if the agent is not vorinostat, is v interesting. It would be helpful to find a safe (ie already approved for human use) agent that will do the job of kicking HIV out of bed to get finally hammered, it woud save so much time.

This is 1990 folks, so 6-10 year wait for a possible pharma cure (in developed countries at least).

In the deckchair but opening the good Scotch.

- matt