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."

[aruanan]

I would be seriously interested in the immunological evidence behind the "most" in that sentence. Because I have a hunch it may have been pulled out of somebody's tailbone, and that actually they flat do not know how many are in the one category, and how many are in the other.

Well, since most patients are progressors and those patients are the ones whose CD8 functions are impaired, and the small balance of non-progressors has a certain percentage whose CD8 functions are more like normal, it's not an unreasonable sentence.

[tortoise]

The epidemiologists that I have talked to tell me that there is no evidence of a mosquito vector at all.

Totally possible. This was a couple years ago. There were two relatively isolated locales that apparently did have an infection pattern compatible with a mosquito vector that they were very interested in. However, there could be other social/cultural causative factors. Hell, there are isolated populations in the nether regions of the U.S. where the HIV infection rate is >70% (like on some Indian reservations). Depending on local practice and custom, you could find HIV in literally anyone, which may have been the case here.

[OldFriend]

Perhaps this is why Magic Johnson has not contracted AIDS, despite being diagnosed with HIV so many years ago.

[JasonC]

Helps, but not answers. One, the large SF study says 5% for its non-progressor definition not 1-2%, but also says 21% of HIV+ will not have developed AIDs 15 years after infection. That is distinctly higher than your 1-2%. Which I suspect is more like the ratio of non-progressors to all HIV positives. It is also for only one population, which may be typical or may not be.

Two, the definitions are all over the map - some 6 years, most 7, the SF study 10 years. Some specify no anti-virals for the non-progressor definition, without saying whether the comparison groups are or aren't also no anti-viral classes. One study finds strong evidence that strains of HIV exist that do not cause disease, probably as a special case but also a monkey wrench thrown into non-progessor statistics.

Most of the rest of the studies there manage to show that defined non progressors really are healthier, not just taking longer, which is a rather limited statement that should surprise no one (since they are selected-defined as HIV+ for long periods with good blood scores and no AIDs).

Obviously, the studies are primarily designed to address guesses about how it is working or what subsystem is involved. They are not primarily directed at mapping the epidemology (how many go from this to that category in this or that long, etc). The result is less than a clear picture, but certainly I see nothing so far to support the "1-2%, corrected for everything" figure.

[JasonC]

Most patients are progressors because they are patients. Non-progressors don't walk in sick. It is not at all that simple.

[JasonC]

You have to include everything in the selecting of non-progressors. Which does not begin from "patients". When someone develops AIDs, you know they have it. (They have HIV, because that is part of the definition of AIDs). Then some group of contacts know they are at risk and are tested. Some get tested on their own initiative because they know they are in risk groups, or because they are particularly nervous or careful or can afford it or some institution makes them. Nothing like everyone exposed gets tested, and those that are involve detection failures, and a distribution of time lags between exposure and detection, etc.

Then for another monkey wrench, take the case of a mutated strain that infected 7 in Australia through a blood screening failure. None of the 7 has developed AIDs. Why do we even know it happened? Because of the manner of infection - transfusion - and screening procedures caught the HIV positives despite a complete absence of symptoms. Now, can that happen with sexual tranmission in some subpopulation in New Orleans? Sure. Would be ever know about it? We'd probably eventually see a portion of the HIV positives, because of a random testing "hit" within that subpopulation etc. Would we see all of it? No. Would such cases show up in a general survey of the incidence of HIV positives? A random one yes, a patient one no.

You have to be very careful with definitional and observational bias issues when making statements about epidemic categories...

[aruanan]

Most patients are progressors because they are patients. Non-progressors don't walk in sick. It is not at all that simple.

Think of it. You're arguing from ignorance. Bad move. Though we may not know the total numbers either of those who are progressors or those who are not (for the very simple reason that one cannot have omniscient knowledge of all members of any extremely large and constantly changing category, though one can come to have pretty solid statistical knowledge), of those who are tested, found to be HIV positive, and who are tracked, the majority is found to consist of progressors. This may not be exhaustive knowledge, but it's far more solid than categorical games such as Most patients are progressors because they are patients. Non-progressors don't walk in sick. It is not all that simple.

[sneakypete]

You are of course correct about the behaviour component of AIDS as a disease, but the research into the mechanisms of immunology can benifit a host of diseases.

Nobody on FR wants to hear that. They want to hear about people suffering terrible deaths because they had sex,and this "made Gawd angry enough to give them the punishment they deserve".

[sneakypete]

What we are learning about the immune response via AIDS research is leading to developments across the human disease spectrum.

We are not only learning a lot about acquired diseases,but also diseases that occur at the genetic level that are inhierited (like diabetes),and other birth defects. We could even learn to create genetic "triggers" that could be injected into the body to get the body itself to kick in and cure itself.

[Greeklawyer]

too much profit in treatment, not enough profit in cure.
(vaccine perhaps)

[Neuromancer]

Thank you for returning this post to the Sidebar last night.

[aruanan]

too much profit in treatment, not enough profit in cure. (vaccine perhaps)

The number of camels you've swallowed while straining for a few gnats is amazing.

[tallhappy]

For more that four years I have been posting breaking news from the world of Virology on Free Republic.

And how many times have you posted articles just like this one where the "cure for Aids" (CFA) is just around the corner based on great new findings?

This is the latest iteration on the CFA -- finding LTNPs (long term non-progressors) and the difference between them and those who get sick.

David Ho Ho Ho just came out with his (defensins) last week. These guys you cite today have theirs. Robbie Gallon of Gallo says he knows what it is and cannot say yet because it is a secret.

And other celebrity scientists (take money as scientists and play then on TV and at federal hearings) chimed in also saying they have what it is.

[tallhappy]

The sad history of PC in the AIDS pandemic is all too true

Usng the term "pandemic" makes you PC as well.

[tallhappy]

There exists a mutation in the gene that codifies for the CCR5 molecule...

Codifies?

[Atlas Sneezed]

I thought AIDS had been cured:

The cure? Use a condom and don't share needles.

[mamelukesabre]

The probably point of origin(sweden) makes sense I guess, in that it is also the probably point of origin of the pigmentation impared people(a.k.a. blue eyed blonds and ruddy complexions).

Seems to be a pattern here that seems to turn up over and over. THat is that white people, compared to other races, are of a very small gene pool and seem to have an unusual resistance to disease. Being a lay person in these matters, I will draw a conclusion without understanding all the technical details: The mystical "north man" is likely the father of all white people on the planet and this odd barbarian race developed in very harsh conditions burdened by a plethora of disease and pestilence and it is the north man genes in white people that give them an advantage against disease.

I read once that the common house fly, the common brown rat, the human flea, and something else that I don't remember(possibly lice or scabies or something like this)....were all completely unknown to the whole world untill the viking invaders brought these pests with them on their invasions into europe and elsewhere. I wouldn't be the least bit surprised if someday researchers prove that venerial deseases were introduced to the romans by the vikings as well.

[JasonC]

A known selective effect distorting a sample is not "ignorance". And no mythical exhaustive knowledge of a category is needed to minimize the distortion produced by this selection effect (which, in case anyone is having trouble tracking, is people with symptoms already being selected as progressors). You would use a cohort track of a random sample, e.g. from some regular institutional screening procedure, say, including negatives and a-symptomatic positives. You would get a measure of prevalence of each category in the general population as a result. Two or three such cohort studies in different places, with different reasons for the screening, would improve confidence in the results. It is not a question of mining bad data not directed at the question asked, nor merely speculating about the question asked in the absence of good data. It is a question of going out and getting good data.