Unlocking HIV's Drug-Proof Fortresses

Scientists Exploring Whether Parasite Drug Can Be Key To Reaching AIDS Virus Hideouts In Body

(AP)  The AIDS virus has hideouts deep in the immune system that today's drugs can't reach. Now scientists finally have discovered how HIV builds one of those fortresses - and they're exploring whether a drug already used to fight a parasite in developing countries just might hold a key to break in.

Researchers have long struggled unsuccessfully to attack what they call reservoirs of dormant HIV, and the new work is in very early stages.

But University of Rochester scientists say it may be fairly straightforward to attack one of these reservoirs, blood cells called macrophages that HIV hijacks and turns into viral hideaways.

The new discovery shows the exact steps that HIV takes to do that - and found that some existing drugs, including a long-used treatment for leishmaniasis called miltefosine, can block the main step and thus cause these cells to self-destruct.

"It's a very smart virus," said lead researcher Dr. Baek Kim. "They have to have a very good fence to protect their house for a long time. ... Get rid of the fence, and now their house is gone."

Today's drugs have turned HIV from a quick death sentence into, for many, a chronic infection. Yet those drugs don't eliminate HIV because they can't reach the two known pools of cells where the virus can lie dormant, ever ready to resurface.

So-called memory T cells form one such pool. As the name implies, these are the cells that ensure if you get, say, measles as a child, you're forever immune. They live for years, even decades, making them a logical HIV hideout, and one that scientists have repeatedly sought to dismantle to no avail.

Macrophages, another type of immune cell, form the second pool. They roam the body looking for invaders like bacteria to gobble up. If they get harmed, such as becoming infected by a virus, they're supposed to commit suicide. But HIV instead keeps them alive long past their normal lifespan.

"Up to now, nobody has really thought about how to eliminate the macrophage reservoir," said Dr. Kuan-Teh Jeang, an HIV specialist at the National Institutes of Health. "The imagination now has turned toward, 'How do we eliminate reservoirs?' ... The best way to address our problem is to simply kill those cells."

The Rochester team found that HIV produces a protein that turns on a particular cell-survival pathway. After a multistep process, it ultimately activates an enzyme called Akt that in turn prevents cell suicide, the researchers reported Thursday online in the journal Retrovirology.

That was good news, Kim said, because the Akt pathway is a culprit in certain cancers - meaning oncologists have been trying to target it for some time. So Kim put human HIV-infected macrophages in lab dishes and started adding drugs known to block the Akt pathway, to see if any killed the cells.

He had luck: Miltefosine and a cousin named perifosine both rapidly killed the macrophages, thus depriving HIV of this hideout.

Perifosine is currently being studied as a possible cancer drug. But miltefosine is known to be safe through its use in leishmaniasis patients. So Kim's goal is to rapidly study the already available miltefosine in animals, to see if it truly targets infected macrophages well enough to then test in HIV patients.

"The evidence they show is in fact pretty good," said NIH's Jeang, who says the next step should be a test of miltefosine in monkeys infected with SIV, the monkey version of the AIDS virus.

[brianbwb-2009]

Posted by tiddsanbeer

You forgot a few,

No blood transfusions

No organ transplants

Keep your mouth closed (no oral s-e-x)

No contact sports

[redhoffer]

Dan9111- You have lied in your post, there is very promising research that says circumsision hugely decreases the risk of HIV transmission, in fact they stopped one study in Africa as it seemed unethical to withold this effective treatment from the control group. You are a sick liar, shame on you. Anyone can google the data.

Denn- Um, heterosexual women are the highest group of persons getting HIV, many from the husbands and boyfriends. You are against people getting married and having ***? It''s people like you have support abstinence based education and get to see their kids and the neighborhood kids get increasing rates of STD''s and HIV, as well as pregnancy. Way to go, your hatred for the children is sickening. Why else would you support programs that lead to increased risk of HIV and pregnancy.

[denn034]

The story states: "Today''s drugs have turned HIV from a quick death sentence into, for many, a chronic infection." Yeah, an extremely painful "chronic infection" that ultimately kills them. There''s also the issue of the "long and productive" proverty inducing cost of the drugs as well. Your comment CBS can only promote the very behavior that leads to AIDS and that''s disgusting, shame on you.

[denn034]

Cure one strain and another superstrain that resists all known cures comes along. Stories like this can only result in less restraint where high risk behavior is concerned. In the end, AIDS targets homosexuals, bisexuals, and drug addicts as per a statistic in the 2002 World Almanac and we should be about stopping the spread of AIDS by discouraging such behavior. Period!

[dan9111]

Why are they trying to "find HIV"? Not too long ago, we were told it was hiding in baby boys genitals and that mutilating baby boys in their crotches would cure AIDS. We are supposed to take these HIV researchers seriously after their circumcised-peniss theory disproven by men across America?

After they condone sexually attacking boys in the hospital, I am pretty sure these folks are dangerous pedophiles. If you see them dying of AIDS, we are supposed to believe it is a macrophage reservoir and that mutilation is a magic cure-all. Got it. Science has come a long way. These guys are truly selling modern-day snake oil.