The secret of long term non-progressors (HIV+ but never developing AIDS) may have been discovered

Nature Immunology (DOI:10.1038/ni845) via New Scientist ^ | 10-06-02 | Philip Cohen

[Neuromancer]

Another theory has emerged to explain why some HIV-infected patients stay healthy despite years of infection. Researchers in the US and the Netherlands have traced the ability to immune cells that replicate rapidly.

Immunologists have long been eager to crack the secret of long term non-progressors - HIV-infected patients who never develop the health problems of AIDS. For 16 years researchers have thought the answer might lie in a product of immune cells called CD8 T cells.

Sometimes called killer T cells for their ability to destroy cells infected with virus, researchers had found the CD8s also spray out a small, unidentified protein that can halt HIV replication without killing cells. Just last week, researchers in New York announced they might have identified this elusive CD8 antiviral factor (CAF), though that claim remains controversial.

But CAF may not be the whole story, says Mark Connors at the National Institutes of Health near Washington DC. He is working with a subset of nonprogressor patients whose blood virus level is so unusually low it typically cannot be detected by standard tests.

In these patients, Connors says secreted proteins do not seem to be responsible for the protection. "We've tested for many proteins and drilled a lot of dry wells for a number of years," he says. "So we're happy we found this."

What Connors and his colleagues found was that the CD8 T cells in his extreme group of patients started replicating rapidly in response to HIV-infected cells, while that was not true in patients in which the disease had progressed.

Intriguingly, as the cells started multiplying they also switched on proteins for attacking virus-laden cells. That suggests that if the cells do not multiply, they are not properly primed for battle. Now the researchers are investigating how the CD8 cell's replication ability is closed down in most HIV-positive patients.

This is an important question since the majority of vaccine strategies against the virus are meant to stimulate the killing function of CD8 T cells. "Ideally the vaccine would prevent that phenomenon we see in progressors," Connors says. "And in infected patients, we'd like to reverse it."

[Honorary Serb]

It's good to read some good news on the research front on this forum, rather than always the usual bad news (whether posted by me or by others).

As for cancer versus AIDS research--I know a thing or two about both. Cancer is really many diseases, and it is quite insidious--the tumor cells tend to mutate or exercise some other types of defenses to defeat a lot of what researchers throw at it. For example, several cancer drugs have failed in clinical trials this year.

However, we are also beginning to figure out how to develop some new "designer drugs" against specific types of cancer. (The first one is Gleevec.) It's a step-by-step process--there's no one magic solution. So throwing lots of money at cancer without effective ways of thinking about how to approach each type of the disease does not work.

The bottom line is that what we've been spending on AIDS did not necessarily hurt our progress in cancer. And the new finding on AIDS may well help us on a broad front--there are many immune and infectious diseases that it might possibly apply to. But as you probably know, I am against "political correctness" in all its forms anyway!!!!

[tortoise]

You are referring to a specific genetic sequence found in northern European populations that confers immunity to ~1% of the population and resistance to 10-20%. This is generally true with virtually any disease you can name. There are enough humans alive today with sufficiently diverse genomes that while a particularly nasty plague could make a dent in the population, it would leave enough people alive to have a healthy genome population.

[Neuromancer]

Among the chemokine receptors, CCR5 and CXCR4 are the main coreceptors for HIV entrance. There exists a mutation in the gene that codifies for the CCR5 molecule which confers a high degree of resistance to HIV infection in vitro and in vivo.

This mutation named 32 consists in a 32 base-pair deletion that encodes for a non-functional protein, and as a result it is not expressed in the cell membrane. Homozygous individuals for this mutation do not have any known immunologic or biologic alteration.

The 32 allele is present mainly in Caucasian population.

In the United States the frequency is 8% to 10% in white population but less than 1% in Afro-American individuals. There is also a very low frequency of the mutation among Caucasians in Asia (Pakistan and India) and it has not been reported in China, Japan or pure African population.

[RobbyS]

Unsaid is how many of these patients have changed their lifestyle.

[tortoise]

Amazing, a disease that can be prevented by proper behavior choices.

Ignoring the fact that a HUGE amount of general anti-viral technologies have come out of the HIV problem (before which, we had literally no anti-viral capability). So it has definitely helped everyone. I personally know people who have been successfully treated for nasty non-behavioral viral diseases with drugs that came out of HIV research.

That said, I've had a couple epidemiologists tell me that they suspect there may now be a mosquito vector for HIV. While there is no conclusive proof at this time, there are at least two distinct locales of the world (one in southeast Asia and one somewhere in Africa) where they have seen infection patterns that are consistent with mosquito vectors that have not yet been explained. You may not care about HIV today, but you may very well care tomorrow.

[sheik yerbouty]

It must be the miracle drug Trinoasitol!

[Neuromancer]

Frequency of Mutant Allele in Europe and Africa

Sweden = 13.7%; (probable point of origin)
Russia, 13%.
Italy, 5.3%.
Turkey, 6.3%

[Neuromancer]

Jason when we say 1% or 2% it is factoring in all the very salient points you mention.

[Archie Bunker on steroids]

Wow! I can't imagine four close relatives suffering through hemophelia, then AIDS. I'm sorry.

I can only imagine how you're family felt. Trusting a treatment tainted by disgusting humans.

[Archie Bunker on steroids]

Many believed the mosquito theory about 20 years ago. I lived in south Florida at the time & people started using lots of bug dope. I hope this is not true. West Nile virus is vectored by mosquitos though.

[lafroste]

Among the chemokine receptors, CCR5 and CXCR4 are the main coreceptors for HIV entrance. There exists a mutation in the gene that codifies for the CCR5 molecule which confers a high degree of resistance to HIV infection in vitro and in vivo. This mutation named 32 consists in a 32 base-pair deletion that encodes for a non-functional protein, and as a result it is not expressed in the cell membrane. Homozygous individuals for this mutation do not have any known immunologic or biologic alteration. The 32 allele is present mainly in Caucasian population. In the United States the frequency is 8% to 10% in white population but less than 1% in Afro-American individuals. There is also a very low frequency of the mutation among Caucasians in Asia (Pakistan and India) and it has not been reported in China, Japan or pure African population.

Boy I wish you know-nothings would back up your vague generalities and unsupported theses with at least a shred of insight and a few facts to back your foggy reasoning!

just kidding :)

[Post Toasties]

Drive a large vehicle carefully and stay healthy, so you minimize your chances of needing a transfusion.

[lafroste]

I would be lying if I said I understood your post. Socialists? I'm going to Japan? WTF, Over...

[JasonC]

Who is "we", and what are the absolute numbers in each category, just in the US? (Since I expect data is spotty elsewhere, but the CDC should have reasonably good numbers for here).

[NotJustAnotherPrettyFace]

Bump for a later read.

[Post Toasties]

That, of course, flies in the face of the heated 'assurances' by US health 'authorities' that it is impossible for mosquitoes to transmit the AIDS virus.

[tortoise]

Many viral mosquito vectors can only be transmitted by a specific species of mosquito. This is almost certainly true in this case (if it turns out to be true at all). As far as I know, it is true that American mosquito varieties cannot transmit HIV. A question apparently remains about some foreign varietals.

[Neuromancer]

Perhaps this will help:

LTNP

Best Regards,

Good Night All

[Doctor Stochastic]

The epidemiologists that I have talked to tell me that there is no evidence of a mosquito vector at all. There aren't enough childred being infected to blame mosquitos. The distribution of infection should look like malaria or yellow fever or west nile if mosquitos were a vector.

This doesn't mean that such a vector could not arise.

[aruanan]

Had we poured that kind of money into cancer, it is unlikely that people would have to suffer through chemo & agonizing death.

Hardly. But the total amount spent on cancer to date is pretty staggering. If as much had been spent on cancer over the same time span as on HIV and related virus research, the possibility of a cure for cancer would be much less certain than developing a cure for a virus because "cancer" is a catch-all term for many, many different diseases that have many different causes (some of them viral--so at least here the research done on HIV has a directly applicability to virally-related cancers). The likelihood is for emerging diseases to be viral in nature, not bacterial. The knowledge gained in studying the onset and progression of a viral disease has had and will have a great impact on medical science because there is protection against only a relatively few viral diseases to date.