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Medical Forum / Diseases and Disorders / AIDS / May 2007Scientists refute HIV theory
Is the penny starting to drop? <http://www3.imperial.ac.uk/newsandeventspggrp/imperialcollege/newssummary/news_2 2-5-2007-10-16-27?newsid=11714>: "Scientists have refuted a longstanding theory of how HIV slowly depletes the body's capacity to fight infection, in new research published today. [...] One popular theory has been the 'runaway' hypothesis, which says that T cells infected by HIV produce more HIV virus particles, which activate more T cells, that in turn become infected, leading to an uncontrolled cycle of T cell activation, infection, HIV production and cell destruction. However, today's new study in PLoS Medicine shows that this theory cannot explain the very slow pace of depletion that occurs in HIV infection."  Signature<http://www.hiv-poz.co.uk/> >Is the penny starting to drop? It did for Michael Bellefountaine. He followed his friend, David, into death by AIDS needlessly because he bought your stupid lies. >>Is the penny starting to drop? >It did for Michael Bellefountaine. He followed his friend, David, into >death by AIDS needlessly because he bought your stupid lies. You can't blame that on me. Michael and David were questioning HIV=AIDS=Death a long time before me. Signature<http://www.hiv-poz.co.uk/> >>>Is the penny starting to drop? > [quoted text clipped - 3 lines] >You can't blame that on me. Michael and David were questioning >HIV=AIDS=Death a long time before me. I'm not blaming you for it.....I am warning you that following their path is extremely dangerous. In their case, denial was deadly. >Is the penny starting to drop? > [quoted text clipped - 3 lines] >depletes the body's capacity to fight infection, in new research >published today. Oh--and this merely refutes Ho's "Tap-and-Drain" model which is not the least bit surprising nor particularly news. It does NOT say ANYTHING that supports the notion that HIV does not cause AIDS. Quite to the contrary. Indeed, I and others rejected Ho's model back in the 90s when it came out as being inadequate to describe HIV disease pathogenesis. Further, this supports the point I was making that you knee-jerk denialists f.ck up this FAR more important discussion because you can't get to square one, living in your delusional la-la land. How many more people will you murder with this bullshit? George M. Carter >[...] > [quoted text clipped - 7 lines] >cannot explain the very slow pace of depletion that occurs in HIV >infection." >>Is the penny starting to drop? >> [quoted text clipped - 3 lines] >>depletes the body's capacity to fight infection, in new research >>published today. >Oh--and this merely refutes Ho's "Tap-and-Drain" model which is not >the least bit surprising nor particularly news. Ah yes, you have your pet theory that CD4 cells suddenly commit suicide for no apparent reason. I don't find it very convincing. >Further, this supports the point I was making that you knee-jerk >denialists f.ck up this FAR more important discussion because you >can't get to square one, living in your delusional la-la land. What's the more important discussion? Signature<http://www.hiv-poz.co.uk/> >>>Is the penny starting to drop? >>> [quoted text clipped - 9 lines] >Ah yes, you have your pet theory that CD4 cells suddenly commit >suicide for no apparent reason. I don't find it very convincing. Excuse me?? "No apparent reason" is your commentary. There are plenty of proposed mechanisms for CD4 death. What brought your CD4 count down so low? >>Further, this supports the point I was making that you knee-jerk >>denialists f.ck up this FAR more important discussion because you >>can't get to square one, living in your delusional la-la land. > >What's the more important discussion? Understanding how and why CD4 counts are depleted, which can have therapeutic implications. Oxidative stress is probably one of the mechanisms that cause CD4 count depletion. Other forms of immune dysregulation are understood. Destruction of neurons is undoubtedly due to inflammatory cytokines and products released by HIV infected glial cells. Just a few examples of mechanisms that indeed have potential therapeutic implications. George M. Carter >>Ah yes, you have your pet theory that CD4 cells suddenly commit >>suicide for no apparent reason. I don't find it very convincing. >Excuse me?? "No apparent reason" is your commentary. There are plenty >of proposed mechanisms for CD4 death. I thought your theory was that CD4 sat around ignoring HIV for a few years, then suddenly committed hara-kiri for bringing shame on the immune system. >What brought your CD4 count down so low? We've already discussed this. You don't like my suggestions and I don't like yours. Some I put forward included natural decline, depression, being healthy. Wikipedia suggests CD4 was discovered in 1985 to support the HIV theory. <http://en.wikipedia.org/wiki/CD4>: "CD4 (cluster of differentiation 4) is a glycoprotein expressed on the surface of T helper cells, regulatory T cells, monocytes, macrophages, and dendritic cells. It was discovered by Steven McDougall in 1985, while he was looking for the binding site of HIV to T-lymphocytes." >Understanding how and why CD4 counts are depleted, which can have >therapeutic implications. Oxidative stress is probably one of the >mechanisms that cause CD4 count depletion. Erm, hold on a second. Isn't that the same theory suggested by the Perth Group 'denialists?' Signature<http://www.hiv-poz.co.uk/> >>>Ah yes, you have your pet theory that CD4 cells suddenly commit >>>suicide for no apparent reason. I don't find it very convincing. [quoted text clipped - 5 lines] >years, then suddenly committed hara-kiri for bringing shame on the >immune system. I've never expressed such an odd theory. Those are your clumsy words and confused thoughts. >>What brought your CD4 count down so low? > >We've already discussed this. You don't like my suggestions and I >don't like yours. Some I put forward included natural decline, >depression, being healthy. "Being healthy" causes CD4 decline? And on what evidence do you base and chronic, persistent and severe decline of CD4 counts being caused by "natural decline" or depression? What evidence do you have for any of these absurd notions? >Wikipedia suggests CD4 was discovered in 1985 to support the HIV >theory. <http://en.wikipedia.org/wiki/CD4>: [quoted text clipped - 3 lines] >and dendritic cells. It was discovered by Steven McDougall in 1985, >while he was looking for the binding site of HIV to T-lymphocytes." Perhaps so. >>Understanding how and why CD4 counts are depleted, which can have >>therapeutic implications. Oxidative stress is probably one of the >>mechanisms that cause CD4 count depletion. > >Erm, hold on a second. Isn't that the same theory suggested by the >Perth Group 'denialists?' The Perthies have a dismal grasp of the science. No, it's not the same because they think they're smarter even than that jackass Duesberg and claim that HIV doesn't exist. Oxidative stress on its own does not cause a chronic depletion of CD4 counts--but it may be one of the mechanisms that HIV infection initiates. George M. Carter "GMCarter" <fiar@verizon.net> wrote in message > a dismal grasp of the science. > > Oxidative stress on its own does not cause a chronic depletion of CD4 > counts--but it may be ... this or that or perhaps something else, maybe. It is certainly true that the Perth Group do not know everything about what can cause CD4 depletion, but: 1. Nobody does. 2. Low CD4 cells counts are a "marker," and there is no direct correlation between this marker and "AIDS." In other words, until a doctor can say, "you have a CD4 count of X, and so you will die within three to five months" (and have it actually happen all the time), one can only take this marker with a grain of salt. It is not uncommon for those who are "HIV negative" to have low CD4 counts, for no apparent reason! Ask people in the life insurance industry. 3. "Oxidative stress" is contextual, that is, there are factors which influence how dangerous this is. One factor is the kinds of fatty acids one has in one's cells that the body uses to make inflammatory metabolites. "HIV/AIDS" occurred at the exact time the first generation of young (sexually active, obviously) adults with arachidonic acid in their cells decided to not only have sex, but to take drugs, etc. It is likely that the combination of factors in their lifestyles led to their "AIDS" (the minority who got "AIDS," that is). This is easy to demonstrate in an experiment in which gay young men are exposed to the typical STDs, given large doses of antibiotics, corticosteriods, "poppers," etc., have passive anal sex without condoms with each other, etc. Then after a couple of years of that, you give them AZT for a couple of years, and voila - you have "AIDS" (in the same proportion to those who died of "AIDS" in the gay community in the early 1980s). >"GMCarter" <fiar@verizon.net> wrote in message >> [quoted text clipped - 4 lines] > >this or that or perhaps something else, maybe. LOL...lil death has joined the denialists. You're in good company, dear. > >"GMCarter" <fiar@verizon.net> wrote in message > >> [quoted text clipped - 7 lines] > LOL...lil death has joined the denialists. You're in good company, > dear. Not at all. I am just tired of your caveats with every statement. 20+ million dead of AIDS patients do my talking for proof of the effects. I don't get involved in the why aspects of the drugs, just the personal behavior that led to their death. Now that the blood banks have been made safe for heterosexuals only the at risk hets have to worry about the effects of the poisonous drugs. >> >"GMCarter" <fiar@verizon.net> wrote in message >> >> [quoted text clipped - 9 lines] >> >Not at all. I am just tired of your caveats with every statement. Here's one without caveats: you're an a.shole! LOL. Poor wittle poopy head. Wonder what your last thoughts are gonna be? That you wasted your life wallowing in futile hate? Yeah...probably. > >> >"GMCarter" <fiar@verizon.net> wrote in message > >> >> [quoted text clipped - 11 lines] > > Here's one without caveats: you're an a.shole! In your perverted opinion. > LOL. Poor wittle poopy head. Childish > Wonder what your last thoughts are gonna be? > That you wasted your life wallowing in futile hate? > Yeah...probably. More of your faggot denial double-speak. That question has been asked.......and answered. I told you my last thought will be that I am glad I didn't waste my life as a faggot. Poor Carter, see the faggot does earn its name every-day. snip >I told you my last thought will be that I am glad >I didn't waste my life as a faggot. LOL! And you don't even see how profoundly pathetic that is, do you? Oh my god, you poor, poor dear. I do hope you find healing so that some other thought might pass through that sodden little mind. How angry are you right now? Check your blood pressure! That last thought might be coming sooner than you think!! > snip > >I told you my last thought will be that I am glad > >I didn't waste my life as a faggot. > > LOL! And you don't even see how profoundly pathetic that is, do you? In deed, I see how profoundly pathetic being a faggot is. You see, I am not the one sitting here attempting to lead others down a road they do not wish to travel. You are the one insisting others take your advice or die. Take your recommended meds or die. Live like you say, or die. You truly are one perverted faggot. >> snip >> >I told you my last thought will be that I am glad [quoted text clipped - 3 lines] >> >In deed, I see how profoundly pathetic being a faggot is. You're a pathetic faggot? LOL....good luck and try to find healing, dear. > >> snip > >> >I told you my last thought will be that I am glad [quoted text clipped - 6 lines] > You're a pathetic faggot? > LOL....good luck and try to find healing, dear. LOL, you even attempt to pervert this, how faggot. >>>>Ah yes, you have your pet theory that CD4 cells suddenly commit >>>>suicide for no apparent reason. I don't find it very convincing. [quoted text clipped - 8 lines] >I've never expressed such an odd theory. Those are your clumsy words >and confused thoughts. Perhaps you don't like my analogy, but you do support the suicide theory, don't you? You mentioned it in another thread. >>>What brought your CD4 count down so low? >>We've already discussed this. You don't like my suggestions and I >>don't like yours. Some I put forward included natural decline, >>depression, being healthy. >"Being healthy" causes CD4 decline? And on what evidence do you base >and chronic, persistent and severe decline of CD4 counts being caused >by "natural decline" or depression? > >What evidence do you have for any of these absurd notions? Well, as I said: we've already discussed this. You don't like my suggestions. What evidence do I have? The very real evidence that I am alive and well at a time when HIV=AIDS=Death statistics, data, and believers tell me I should be extremely unwell and planning my funeral. >>>Understanding how and why CD4 counts are depleted, which can have >>>therapeutic implications. Oxidative stress is probably one of the >>>mechanisms that cause CD4 count depletion. >>Erm, hold on a second. Isn't that the same theory suggested by the >>Perth Group 'denialists?' >The Perthies have a dismal grasp of the science. No, it's not the same >because they think they're smarter even than that jackass Duesberg and [quoted text clipped - 3 lines] >counts--but it may be one of the mechanisms that HIV infection >initiates. It's quite funny the way you share the views of The Perth Group and Duesberg while condemning them at the same time. Signature<http://www.hiv-poz.co.uk/> >>>>>Ah yes, you have your pet theory that CD4 cells suddenly commit >>>>>suicide for no apparent reason. I don't find it very convincing. [quoted text clipped - 11 lines] >Perhaps you don't like my analogy, but you do support the suicide >theory, don't you? You mentioned it in another thread. Apoptosis is not a theory. There are ample evidence to show that programmed cell death is a significant feature of HIV pathogenesis. >>>>What brought your CD4 count down so low? > [quoted text clipped - 13 lines] >believers tell me I should be extremely unwell and planning my >funeral. That's what David P and Michael B used to say. They died of AIDS. This is pretty thin "evidence" - and you're not well. You have HIV. HIV induces immune activation. This increases T cell turnover. It destroys gut function, resulting in increased lipopolysaccharide secretion, which results in further immune activation. This results in oxidative stress, as well as chronic depletion of CD4 numbers, along with other immunological perturbations. The result? AIDS. I agree with the US definition that includes a CD4 count below 200 as a marker for having developed aquired immune deficiency--the syndrome part arises with the dramatically increased risk of opportunistic infections associated with a chronically low CD4 count. George M. Carter >>>>Understanding how and why CD4 counts are depleted, which can have >>>>therapeutic implications. Oxidative stress is probably one of the [quoted text clipped - 13 lines] >It's quite funny the way you share the views of The Perth Group and >Duesberg while condemning them at the same time. >>Perhaps you don't like my analogy, but you do support the suicide >>theory, don't you? You mentioned it in another thread. >Apoptosis is not a theory. There are ample evidence to show that >programmed cell death is a significant feature of HIV pathogenesis. This HIV=AIDS=Death theory is becoming more and more convoluted. Don't you ever look at it and think to yourself 'this doesn't make sense?' Now you want us to believe that HIV doesn't directly lead to T-cell depletion. Apparently it all happens by some indirect process. Perhaps Duesberg is right and HIV is harmless and doesn't deserve the blame it receives. Or, perhaps, it's simply not there at all. >>Well, as I said: we've already discussed this. You don't like my >>suggestions. What evidence do I have? The very real evidence that I >>am alive and well at a time when HIV=AIDS=Death statistics, data, and >>believers tell me I should be extremely unwell and planning my >>funeral. >That's what David P and Michael B used to say. They died of AIDS. > >This is pretty thin "evidence" - and you're not well. You have HIV. My doctor and the UK government disagree with you. I've recently had my application for disability benefit turned down because I am well. >The result? AIDS. I agree with the US definition that includes a CD4 >count below 200 as a marker for having developed aquired immune >deficiency--the syndrome part arises with the dramatically increased >risk of opportunistic infections associated with a chronically low CD4 >count. That isn't how HIV is viewed in the UK. Here HIV is considered, *at worse*, to be a long-term manageable condition. And those diagnosed with HIV can expect to live a natural life-span. Some time ago the UK government stopped publicising HIV and AIDS, and began winding down funding to HIV and AIDS charities. No doubt you'll say that's the policies of a right-wing administration who don't understand the situation and wants to save money. However, AIDS kills a tiny number of people each year here. Last year AIDS deaths totaled less than 500, from a total population of sixty million. You paint a gloomy picture that doesn't represent reality. Signature<http://www.hiv-poz.co.uk/> >>>Perhaps you don't like my analogy, but you do support the suicide >>>theory, don't you? You mentioned it in another thread. [quoted text clipped - 3 lines] > >This HIV=AIDS=Death theory is becoming more and more convoluted. LOL...that's because your construct is faulty. >Don't you ever look at it and think to yourself 'this doesn't make >sense?' No--you go ahead and explain to me why it doesn't. I would ask you the same thing--what makes you think a steadily declining CD4 count being caused by "stress" makes any sense. Or "drugs cause AIDS." There'd be a LOT more cases of AIDS if that were so. >Now you want us to believe that HIV doesn't directly lead to T-cell >depletion. Apparently it all happens by some indirect process. You think disease processes always work just one way??? Are you really that ignorant? And you're betting your life based on this level of ignorance? >Perhaps Duesberg is right and HIV is harmless and doesn't deserve the >blame it receives. Or, perhaps, it's simply not there at all. La-la-la-la....perhaps little fairies will sprinkle magic pixie dust on your weenie and make your CD4 count jump magically! Oh! Let's buy some pretty pink balloons to celebrate.... Ah...can you see "intellectually bankrupt response"? I thought not. >>>Well, as I said: we've already discussed this. You don't like my >>>suggestions. What evidence do I have? The very real evidence that I [quoted text clipped - 8 lines] >My doctor and the UK government disagree with you. I've recently had >my application for disability benefit turned down because I am well. Eh. If you're well, you shouldn't be on disability then, should you? Why not get a job? >>The result? AIDS. I agree with the US definition that includes a CD4 >>count below 200 as a marker for having developed aquired immune [quoted text clipped - 5 lines] >worse*, to be a long-term manageable condition. And those diagnosed >with HIV can expect to live a natural life-span. Yeah--if you use ARV. If you refuse the ARV--chances are you'll develop an OI and die. This is just wandering away from the issues raised above though. >Some time ago the UK government stopped publicising HIV and AIDS, and >began winding down funding to HIV and AIDS charities. Perhaps true. But then Tony Blair decided it was better suck George Bush's nasty floppy cock and throw away lives in Iraq. >No doubt you'll say that's the policies of a right-wing administration >who don't understand the situation and wants to save money. Ask Tony. >However, AIDS kills a tiny number of people each year here. Last year >AIDS deaths totaled less than 500, from a total population of sixty >million. That's encouraging. I hope it indicates fewer new infections and better treatment outcomes. >You paint a gloomy picture that doesn't represent reality. No dear--I paint a gloomy picture for denialists who pretend that all is well and then fail to take care of themselves. And a gloomier picture for those who WANT access to ARV but cannot because of the unmitigated and genocidal greed of the pharmaceutical industry. George M. Carter "GMCarter" <fiar@verizon.net> wrote in message > Ah...can you see "intellectually bankrupt response"? Yes I can. Most of your responses are like that. > I thought not. LOL, you thought. Now that is funny. > >>That's what David P and Michael B used to say. They died of AIDS. No they died because they let an infected dick f.ck them where a dick is not intended to be. > ...unmitigated and genocidal greed of the pharmaceutical industry. Communist Carter hates to see the free market at work. Get Fiar to send them free meds. Get ACT-UP to send free meds. Get the faggot rainbow group to send free meds. >>This HIV=AIDS=Death theory is becoming more and more convoluted. >LOL...that's because your construct is faulty. It's not my construct. You've told me many times that HIV leads to AIDS which leads to death. >>Don't you ever look at it and think to yourself 'this doesn't make >>sense?' >No--you go ahead and explain to me why it doesn't. It doesn't make sense because you have to keep shifting your position and coming up with new excuses to keep your HIV dream alive. I've seen a change in your stance during the past few days: you've even aligned yourself with The Perth Group. >I would ask you the same thing--what makes you think a steadily >declining CD4 count being caused by "stress" makes any sense. Or >"drugs cause AIDS." You asked why my CD4 count has declined. I looked at what was going on in my life and put forward some suggestion. I think you need to get over your relentless obsession with CD4 counts. Apart from in the US, CD4 count does not diagnose AIDS, and I've seen no long term CD4 count data from HIV- and healthy people to use as a comparison. It's interesting that you don't mention HIV viral load results very much. You'd expect a measure of how much HIV is in the blood to be a far better indicator of disease progression. But no doubt you know how useless HIV viral load testing is, and that's why you keep quiet about it. >There'd be a LOT more cases of AIDS if that were so. Are you referring to drugs in general or ARVs? I don't think I've ever said drugs in general cause AIDS. AIDS needs an HIV diagnosis first, and I don't believe HIV exists, so I wouldn't argue that drugs cause HIV. There is evidence that AZT caused AIDS-like symptoms as well as many deaths. As for ART, I don't think its effects have been fully realised yet. >>Now you want us to believe that HIV doesn't directly lead to T-cell >>depletion. Apparently it all happens by some indirect process. >You think disease processes always work just one way??? Are you really >that ignorant? And you're betting your life based on this level of >ignorance? After over twenty years of research and spending billions of dollars, HIV researches are still throwing their hands into the air, shrugging their shoulders, and saying 'we don't know.' And you call me ignorant for suggesting that, perhaps, they've got things wrong. Would I be less ignorant if I followed your advice: take the pills and don't ask any awkward questions? >>Perhaps Duesberg is right and HIV is harmless and doesn't deserve the >>blame it receives. Or, perhaps, it's simply not there at all. >La-la-la-la....perhaps little fairies will sprinkle magic pixie dust >on your weenie and make your CD4 count jump magically! Oh! Let's buy >some pretty pink balloons to celebrate.... > >Ah...can you see "intellectually bankrupt response"? Erm, yes. >>My doctor and the UK government disagree with you. I've recently had >>my application for disability benefit turned down because I am well. >Eh. If you're well, you shouldn't be on disability then, should you? >Why not get a job? Because I'm dying of AIDS, aren't I? >Perhaps true. But then Tony Blair decided it was better suck George >Bush's nasty floppy cock and throw away lives in Iraq. Fortunately Bliar's going soon. However, apparently, Gordon Brown is even worse. BTW, is there a rule that all of your Republican presidents have to have some sort of mental health problem, and all your Democratic ones have to be sex mad? :) :) :) >>However, AIDS kills a tiny number of people each year here. Last year >>AIDS deaths totaled less than 500, from a total population of sixty >>million. >That's encouraging. I hope it indicates fewer new infections and >better treatment outcomes. The number of HIV infections is at an all-time high. And the data suggests ARVs have had no positive impact. Signature<http://www.hiv-poz.co.uk/> >>>This HIV=AIDS=Death theory is becoming more and more convoluted. > >>LOL...that's because your construct is faulty. > >It's not my construct. You've told me many times that HIV leads to >AIDS which leads to death. Then you misunderstand. Being born leads to death. HIV is NOT a death sentence any more than life is. MOST people with HIV if they don't seek some kind of treatment will develop AIDS. And MOST people with AIDS who do not receive treatment will die not long after the diagnosis. >>>Don't you ever look at it and think to yourself 'this doesn't make >>>sense?' [quoted text clipped - 3 lines] >It doesn't make sense because you have to keep shifting your position >and coming up with new excuses to keep your HIV dream alive. Not in the slightest. I've been more or less stating the same views about HIV disease pathogenesis. HIV is the primary culprit that initiates chronic immune activation, of which oxidative stress is one significant feature. >I've seen a change in your stance during the past few days: you've >even aligned yourself with The Perth Group. Again, no. The idiots of Perth can't even recognize that HIV exists. >>I would ask you the same thing--what makes you think a steadily >>declining CD4 count being caused by "stress" makes any sense. Or >>"drugs cause AIDS." > >You asked why my CD4 count has declined. I looked at what was going >on in my life and put forward some suggestion. Based on what? Pretty lame suggestions, dear. >I think you need to get over your relentless obsession with CD4 >counts. Apart from in the US, CD4 count does not diagnose AIDS, and >I've seen no long term CD4 count data from HIV- and healthy people to >use as a comparison. You've been shown it and walked away from the data. That's disingenuous. Dangerously disingenuous. >It's interesting that you don't mention HIV viral load results very >much. You'd expect a measure of how much HIV is in the blood to be a >far better indicator of disease progression. But no doubt you know >how useless HIV viral load testing is, and that's why you keep quiet >about it. LOL...that's just f.cking stupid. I also haven't talked about macrophages a lot but I think they're important...you really are desperate, aren't you? Viral load correlates pretty closely with rate of CD4 decline. The test is of less importance to me than it is to others in the world of non-denialists--but it is still important. What matters is how your immune system is doing. It is not doing well at all. >>There'd be a LOT more cases of AIDS if that were so. > >Are you referring to drugs in general or ARVs? No. Try to keep up, dear. If stress, ANY drugs or your other vague handwaving excuses about why your CD4 count is profoundly depleted were accurate hypotheses, there'd be a lot more people with AIDS. There aren't, indicating your theories are baseless. Data tend to refute them. >I don't think I've ever said drugs in general cause AIDS. AIDS needs >an HIV diagnosis first, and I don't believe HIV exists, so I wouldn't >argue that drugs cause HIV. So good luck then. Nothing more to talk about. George M. Carter > Is the penny starting to drop? > [quoted text clipped - 17 lines] > -- > <http://www.hiv-poz.co.uk/> This is actually an interesting study, although they erred somewhat in citing a "runaway hypothesis" because no such hypothesis exists! I emailed the people that put out the press release just to see if they could provide a citation - no answer. I think it represents their take on the published immune activation data, but it was a little foolish to put "runaway" in quotes when they aren't actually quoting anyone. The full text of the paper is here: http://medicine.plosjournals.org/perlserv/?request=get-document&doi=10.1371/jour nal.pmed.0040177 I think the first supplemental analysis is particularly interesting: http://medicine.plosjournals.org/archive/1549-1676/4/5/supinfo/10.1371_journal.p med.0040177.sd001.pdf "We assume that in the presence of HIV there is a small probability that any given activation event will lead to the irreversible acquisition of an 'exhausted' phenotype with reduced survival time and lower activation rate. The simulation shows how this model can predict the slow accumulation of this phenotype, progressively lowering T cell counts over a timescale of years." Which of course begs the question, is there any evidence that exhausted T cells accumulate in progressive HIV infection that might support this assumption? And there is a considerable amount, going way back in time and continuing up to the recent discovery of PD-1 as a marker for T cell exhaustion (a few examples are cited below, I've provided full text links wherever possible). http://bloodjournal.hematologylibrary.org/cgi/reprint/79/7/1746.pdf Legac E, Autran B, Merle-Beral H, Katlama C, Debre P. CD4+CD7-CD57+ T cells: a new T-lymphocyte subset expanded during human immunodeficiency virus infection. Blood. 1992 Apr 1;79(7):1746-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=7973455&query_hl=1&itool=pubmed_DocSum Caruso A, Cantalamessa A, Licenziati S, Peroni L, Prati E, Martinelli F, Canaris AD, Folghera S, Gorla R, Balsari A, et al. Expression of CD28 on CD8+ and CD4+ lymphocytes during HIV infection. Scand J Immunol. 1994 Nov;40(5):485-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=16921384&query_hl=9&itool=pubmed_docsum Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, Mackey EW, Miller JD, Leslie AJ, DePierres C, Mncube Z, Duraiswamy J, Zhu B, Eichbaum Q, Altfeld M, Wherry EJ, Coovadia HM, Goulder PJ, Klenerman P, Ahmed R, Freeman GJ, Walker BD. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006 Sep 21;443(7109):350-4. Epub 2006 Aug 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=17307327&query_hl=6&itool=pubmed_docsum Appay V, Almeida JR, Sauce D, Autran B, Papagno L. Accelerated immune senescence and HIV-1 infection. Exp Gerontol. 2007 May;42(5):432-437. Epub 2007 Jan 8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=16765088&query_hl=6&itool=pubmed_docsum Fernandez S, Price P, McKinnon EJ, Nolan RC, French MA. Low CD4+ T-cell counts in HIV patients receiving effective antiretroviral therapy are associated with CD4+ T-cell activation and senescence but not with lower effector memory T-cell function. Clin Immunol. 2006 Aug;120(2):163-70. Epub 2006 Jun 9. http://www.jimmunol.org/cgi/content/full/175/12/8415 Palmer BE, Blyveis N, Fontenot AP, Wilson CC. Functional and phenotypic characterization of CD57+CD4+ T cells and their association with HIV-1-induced T cell dysfunction. J Immunol. 2005 Dec 15;175(12):8415-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstra ctPlus&list_uids=7911525&query_hl=10&itool=pubmed_docsum Chou CC, Gudeman V, O'Rourke S, Isacescu V, Detels R, Williams GJ, Mitsuyasu RT, Giorgi JV. Phenotypically defined memory CD4+ cells are not selectively decreased in chronic HIV disease. J Acquir Immune Defic Syndr. 1994 Jul;7(7):665-75.
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