Tuesday, October 20, 2009

HIV treatment: the good news and the bad

First, the good news: more people worldwide living with HIV/AIDS are receiving treatment than ever before. Over the last 5 years, there seems to have been a 10-fold increase, and now some four million people are taking antiretroviral drugs. Traditionally, UNAIDS 'epidemic updates' on treatment access in Africa made for depressing reading, with only tiny percentages of HIV-positive persons within African countries being treated. For the vast majority of Africans, HIV/AIDS remained what it was in the beginning, a death sentence, even if had obtained the status of a chronic disease in far-off (and better-off) countries. Now there are three million Africans taking AIDS drugs. This impressive achievement has taken more than a decade of advocacy, negotiations with pharmaceutical companies, creation of cheaper generic drugs, lobbying, program development, investments in local capacity ... blood, sweat and tears, in other words.

The bad news. The numbers of persons 'on treatment' cannot be trusted altogether. The statistics are developed by governments in a vested interest in stating the highest possible estimates. To do otherwise might show incompetence in the use of (mainly external) funding. The numbers also tend to reflect the number of those who were placed on treatment, and not those who later stopped treatment for one reason on another.

But even if the numbers were more trustworthy, there are other concerns. AIDS treatment and care is lifelong. To keep these millions of persons on treatment in the future requires a vast and ongoing investment. The World Health Organization is considering revising its treatment guidelines on account of studies that indicate earlier initiation of treatment increases life-expectancy. More HIV-positive persons will fall into the category of those in need of treatment, and meeting this new demand will add to the already soaring costs. In addition, some of those currently on first-line treatment will develop drug resistance and need to switch to (more expensive) second-line drugs. And last but not at all least, millions of persons continue to be infected by HIV, meaning that the 'treatment pool' will grow larger and larger in the coming years.

The old questions keep coming back: is this magnitude of spending on HIV/AIDS treatment ethically justified? Is it justified when there are other diseases and conditions, causing greater numbers of deaths, but which do not attract nearly the same level of political and financial support? Why not devote greater attention to HIV prevention research or prevention strategies that may help reduce the rate of new infections?

This is becoming a dramatic example of 'hell being paved by good intentions.' Back a few years ago, we had the unacceptable situation of Africans routinely dying of untreated AIDS, while North Americans and Europeans accessed antiretrovirals and went on with their lives. It was a striking case of global health inequality, and no one with any sense of solidarity could fail to be moved by it. But in the process of trying to improve the situation, something else, vaguely Frankensteinian, has emerged. Billions of dollars will need to be spent to keep the (growing) millions of HIV-infected on treatment. This might not be sustainable, and all the spending might not be proportional or fair, but it would also be unwise to stop financing global AIDS treatment programs now that they have been started. Halting treatment would not only spell death for those living with HIV/AIDS, it could also mean creation of new drug-resistant strains of HIV, making prevention efforts more difficult than ever.

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Blogger bobrien said...

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3:26 PM  
Blogger joe said...

Can this method be used to fight HIV???

New gene therapy halts 2 boys' rare brain disease
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Delicious Digg Facebook Fark Newsvine Reddit StumbleUpon Technorati Twitter Yahoo! Bookmarks Print By LAURAN NEERGAARD, AP Medical Writer Lauran Neergaard, Ap Medical Writer – Thu Nov 5, 5:12 pm ET
WASHINGTON – French scientists mixed gene therapy and bone marrow transplants in two boys to seemingly halt a brain disease that can kill by adolescence. The surprise ingredient: They disabled the HIV virus so it couldn't cause AIDS, and then used it to carry in the healthy new gene.

The experiment marks the first time researchers have tried that long-contemplated step in people — and the first effective gene therapy against a severe brain disease, said lead researcher Dr. Patrick Aubourg of the University Paris-Descartes.

Although it's a small, first-step study, it has "exciting implications" for other blood and immune disorders that had been feared beyond gene therapy's reach, said Dr. Kenneth Cornetta, president of the American Society of Gene and Cell Therapy.

"This study shows the power of combining gene therapy and cell therapy," added Cornetta, whose own lab at Indiana University has long researched how to safely develop gene delivery using lentiviruses, HIV's family.

The research was published in Friday's edition of the journal Science.

In 20 years of gene therapy research, there have been few home runs and some headline-making setbacks — including a risk of leukemia caused by otherwise successful gene therapy for another rare disorder, "bubble boy disease." That's a risk that specialists hope a lentivirus-based gene therapy will eliminate.

Best known from the movie "Lorenzo's Oil", adrenoleukodystrophy, or ALD, is a rare genetic disease that, in its most devastating form, destroys the coating of nerve fibers in boys' brains. Without that coating, called myelin, the neurological system breaks down. The disease typically strikes between the ages of four and 10, leading to blindness, deafness, dementia and loss of muscle control, and killing them within a few years.

Bone marrow transplants can halt ALD by letting new myelin-forming stem cells take root. But it's difficult to find a matching marrow donor, and the transplant itself is very risky.

So what if stem cells from the boys' own bone marrow could be genetically corrected, eliminating the ALD mutation? To do that, Aubourg's team had to overcome a technical hurdle: Gene therapy works when scientists harness deliver a healthy new gene by attaching to a virus that can harmlessly infect cells. But none of today's so-called gene therapy "vectors" could penetrate enough of the stem cells needed for an ALD treatment to work.

Unlike most viruses, HIV can penetrate stem cells, and it sticks permanently. So Aubourg's team removed the genetic parts of HIV that make it dangerous, leaving basically a scaffolding to carry the new therapeutic gene.

Then they culled stem cells from two 7-year-old boys in the early stages of ALD, and mixed in the healthy gene. The boys underwent bone marrow-destroying chemotherapy and then had their genetically corrected stem cells reinserted.

Two years later, the boys have shown no sign of worsening brain damage and are functioning well with 15 percent of their blood cells producing the healthy protein, said Aubourg, who plans to test the experimental procedure in more patients. An advocacy group, the Stop ALD Foundation, is working to raise money for a similar U.S. study.


On the Net:

Science Web site: http://www.sciencemag.org

11:56 AM  
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