Bonus Round Patient Pages -- Dickie's HIV THEORY.
Presented by Steve Schalchlin's Living In The Bonus Round as a friendly and open educational conversation between patients and health care professionals. We encourage feedback and active participation.


Dickie's Personal HIV Theory.
The FULL MONTY - Chapter 1

by Dick Remley, every doctor's nightmare:



Throughout The THEORY, certain mechanisms -- such as Apoptosis, Syncytia formation and Margination -- have been introduced as models of known biological processes that might fill in some of the details as to how The THEORY accomplishes its goal.  None of these processes are critical to the heart and soul of The THEORY.  They are a means to an end.   Although ALL of these processes are known to occur in HIV infection, in truth, they might not be the most significant factors involved.  Cell death might occur through other processes in addition to apoptosis.  Long-lived HIV infected cells might exist for reasons that are not syncytial.  Infected cells might migrate out of circulation and become sequestered in tissues through means other than margination.

These three processes, however, provided the simplest and most direct means of explaining The THEORY through known biological models.   They may or may not be critical to the process The THEORY attempts to describe.  The THEORY is married to none of them.

What IS critical to The THEORY is its basic framework.  The critical postulates of The THEORY are these:

  1. T-cell depletion is caused by the failure to replace some infected cells, not by the wholesale death of cells.
  1. This failure to replace cells is the result of a failure to receive a "replacement signal" from dying cells.
To my knowledge, neither of these postulates has been proven or disproven (that's why its called "The THEORY" and not "The CERTAINTY").

These two postulates are important, because they help explain most of the anomalies that we see in HIV disease that currently accepted theories do not explain - at least not without great difficulty.

The Currently Accepted Theory (which, hereinafter, we will refer to as "the CAT") is that there is this "raging war" going on between HIV and the human body's ability to replace T-cells.  In the CAT, HIV releases millions - perhaps billions - of viral particles into the bloodstream constantly; and a percentage of these particles infect and kill T-cells in a wholesale slaughter of the body's immune system.  The body responds by pumping out new T-cells as fast as it can.  But the body is apparently supposed to be always just one step behind the virus, and slowly loses the war.

I don't buy it.

This currently accepted explanation seems to me to fall short in accounting for some major anomalies seen in HIV disease.  We will now pit elements of The THEORY against the Currently Accepted Theory (CAT) by exploring some of these anomalies.  In the process, we will likely see The THEORY reconstruct itself.


ANOMALY #1:  HIV viral load (the amount of free-floating virus in the bloodstream) can increase to VERY high levels during outbreaks of other viral illnesses such as herpes or the flu.  Even vaccination can cause an increase in viral load.  But increases under these circumstances are almost always temporary.  Once the illness has passed, HIV viral load tends to decline back to the level it was at prior to the occurrence of the illness.  Why?

If the HIV virus is overwhelming the immune system gradually by some very fine margin of cell-death vs. cell replacement, then these increases in viral load should nearly always be disastrous for the patient.   More virus would mean a greater number of T-cells would be infected, which would mean more infected cells producing more virus and then dying off.  If the immune system is just barely able to keep up with HIV infection in the first place, then this set of circumstances would logically be expected to result in the HIV gaining a decisive edge in this contest.  Viral load would spiral upward, and T-cell counts would crash.   In fact, this usually doesn't happen. Viral load jumps - and then falls back down. Patients usually survive this temporary increase in viral burden relatively unscathed.  How can this be?

I can think of four possible explanations for why this would happen:

  1. The immune system somehow responds more strongly to the increase in viral load, and wipes out the extra burden.
  1. The additional viral particles (virions) formed by this process are non-infectious mutations.
  1. The increase in viral load in the bloodstream does not represent the stimulation of viral replication at all, but is caused by the return to circulation of virally infected cells that are usually sequestered outside the bloodstream.
  1. The increase in viral load represents an increase in free-floating virus that was never all that critical to reducing T-cell counts in the first place (The THEORY).
Now, of the above explanations, # 1 seems to me to be the least likely.  If the immune system can control additional viral load and effectively eradicate it, then why wouldn't it go on to wipe out the rest of the viral particles as well?

Explanation # 1 implies that the immune system commonly gains an edge in the war against HIV.  But, if that were the case, then the immune system ought to be able to wipe out the virus completely, and progression to fatal illness would not occur.  This is obviously not the case, and I am dismissing explanation # 1 on those grounds.

Explanation # 2 (that additional virions produced by environmental factors are almost always noninfectious mutants) seems possible, but has a slight problem: why would the newly stimulated viral growth be any more prone to non-infectious mutation than the virus as it is normally found?  Wouldn't virions produced under most conditions have the same percentage chance of survival as virions formed under normal circumstances?

Explanation # 3 (that the increased viral load represents a return to circulation of infected cells that HAD been sequestered somewhere outside the bloodstream) also seems possible, but you'd still have to explain why the increased viral load isn't doing more damage.  Wouldn't the increased level of virions also give rise to an increase in cell infection and death?  I suppose one could endeavor to explain this by saying that the sequestered cells were always causing the same amount of damage - they just weren't SEEN doing this because they were in sequestration.  The net effect of returning them to circulation would therefore be zero.  But it could also be true that the new virions are largely noninfectious - just as required in explanation #2 above.   For Explanation # 3 to work, it would have to concede at least one (and perhaps both) of two major issues in The THEORY:  That infected cells are often found OUTSIDE the bloodstream, and that they produce virions that are unlikely to infect other cells in the bloodstream.

This leaves explanation # 4:  that HIV virions are USUALLY not responsible for the decline in T-cell counts.  This explanation is not exclusive of any of the other explanations, and declares the increase in viral load largely irrelevant to the outcome of the disease process.

To summarize: of the four explanations, #1 seems impossible, #2 seems improbable, #3 must claim the whole effect is something of an illusion, while conceding at least one key issue to The THEORY, and #4 claims the issue is mostly irrelevant. 

The CAT relies on at least one of the first three explanations being true, while the fourth one MUST be untrue.

The THEORY suggests that explanation # 4 is true regardless of whether any of the others are true or not.

ANOMALY #2:  In a certain, small percentage of cases, patients undergoing successful antiretroviral therapy experience BOTH an increase in viral load, AND an increase in T-cell counts.  The increased T-cell counts tend to be sustained and correlate well with an increase in immune response leading to a favorable clinical outcome.  Why is that?

Again we are faced with the issue of increasing viral load, and we return to the four explanations offered above.

The CAT tells us that the new virions are non-infectious because the antiretroviral therapy has resulted in poorly formed viral particles.  I can believe that.  So, it now looks like the CAT favors explanation #2.  This is the only consistent hypothesis the CAT offers us to explain viral load anomalies.  This suggests that only virions produced under natural circumstances are capable of initiating successful infection leading to viral reproduction and cell death.  To me, that seems possible, but a little hard to swallow.

The THEORY suggests that explanation #4 (that the death of cells is NOT what gives rise to T-cell depletion) would hold true in virtually all circumstances.

I have no problem accepting the idea that any of the first three explanations might turn out to be true - although, clearly we've seen some problems with making them "fit".  The reason explanation #4 was chosen to be incorporated into The THEORY is its pure simplicity.  The other three explanations all require acceptance of the idea that there are times when circulating viral load does not cause a decline in T-cell counts.  Explanation #4 simply says, "Yes: and that is MOST of the time."

As we examine this issue further, you may begin to see why I think explanation #4, as offered by The THEORY, simply collapses the complex arguments implied in explanations #1, 2 and 3 down to a more basic point: virions in the bloodstream are clearly not always deadly, and CAN be controlled by the body's immune system.

There are other, similar circumstances in which increases in HIV viral load do not correlate well with expected disease progression.   However, the situations we examined above are the clearest and simplest examples.   The arguments and explanations in all cases would be the same.  Taken together, the incidence of HIV viral load NOT correlating well with consequent impact on the immune system - while it is the exception rather than the rule - seems to me to be sufficiently high so as to make HIV viral load appear to be useful as a surrogate marker, but not as an explanation for T-cell loss.  Viral load might give you an indication of how many cells are already infected, or the rate at which already infected cells are producing virus, but not of how many cells are likely to BECOME successfully infected through the bloodstream.  If infectivity through the bloodstream were the cause of the decline in T-cell counts, then I would expect there to be a more consistent cause-and-effect relationship between viral load and T-cell counts.

ANOMALY #3:  This is actually more of a puzzle than an anomaly,  because it occurs universally: when HIV viral load is brought under control, T-cell counts do not return to normal automatically.  In fact, recovery of the immune system literally takes years, even in the presence of viral load brought so low as to be undetectable.  If there really were a raging battle going in which the body was constantly replacing rapidly disappearing T-cell populations, then removal of the causative factor ought to result in an immediate huge jump in T-cell counts to nearly normal levels.  This just simply NEVER EVER happens.  I've never seen it occur even once.  I've never heard of a REPORT of it happening.   Immediate and significant T-cell increases do occur, but not in huge numbers.   T-cell counts increase gradually over a period of years - and usually in spurts.   Why?

I've never seen a really satisfactory explanation of this that adheres to currently accepted theories.  The closest anyone has ever come to an explanation involves thymic function: T-cells are said to "mature" in the thymus gland.  The condition of the thymus declines with age, and could decline even more rapidly in the presence of disease. Therefore, CD-4 replacement would be retarded.

The problem with this explanation is that it is not really consistent with the description of slowly declining T-cell numbers being caused by a war between HIV and the body's ability to replace T-cells.  Supposedly, the reason for the decline in numbers of T-cells occurring slowly over a number of years is because HIV has a slight edge over the body's replacement capabilities.  The CAT describes the body as being unable to replace CD-4 cells quite as quickly as HIV destroys them, and so the body gradually loses the war.  But, if this is true, then where did all those replacement CD-4 cells that DID appear during this "war" come from?   Didn't THEY require a healthy thymus in which to mature?  What happened?   Did the thymus suddenly "poop out" just at the moment when effective treatment was applied against the virus? In EVERY patient? ALL THE TIME?!?


It seems far more likely to me that the cells are being replaced as they die off.  Remember that current treatments do not kill off infected cells - they only curtail viral reproduction. (Think of it as being more like a chastity belt than a gunshot to the head.)  If certain cells are exceptionally long-lived, then they will be replaced only after a long time passes.  And a cluster of cells dying out all at once would create a "spurt" of  replacement.   Syncytia are sometimes described as "cell clusters". Hmmmm...

But wouldn't the replacement of dying cells require some sort of signal from the cell to the body that death was occurring?   Hmmm...

(But let's not get ahead of ourselves.)

There are other, more scientific, reasons for doubting the thymus hypothesis.  Some studies have been published comparing the rate of T-cell replacement in persons with a relatively normal thymus gland to that of persons whose thymus has been completely removed.  I am aware of at least one study that concluded there was no difference.

I have heard it rather peripherally argued that the NUMBER of T-cells that re-appear in the bloodstream is not what is significant: what counts is whether they are mature and functional.  It is argued that patients need a healthy thymus in which these cells can mature to a more functional state.  I have two replies to that:  First, the NUMBER of T-cells is precisely what we are talking about, since that is the most commonly used way to monitor recovery in AIDS patients.  Secondly, in my involvement with lending support to AIDS patients, I spent a lot of time in hospitals and hospices.  When effective drug treatment finally became widely available about three years ago, the "AIDS wards" of hospitals and hospices emptied out literally in a matter of weeks.  Patient recovery was so startlingly rapid that it placed a financial strain on some hospitals and doctors whose practices consisted largely of HIV-positive patients.  If those new T-cells weren't working, I'd like to hear a really good alternative explanation for why that happened.

Don't get me wrong: I think it is better to have a healthy thymus than NOT to have one.  I just don't think it figures critically into this issue.

To recap a bit: among the things that the CAT has asked us to accept so far, are the following two premises:

  1. Free-floating virus in the bloodstream does not ALWAYS result in cell death and the decline in T-cell counts.
  1. Many of the T-cells that DO die get replaced - and rather rapidly, at that.
There may be more than one way to skin a cat; but the more you scratch the surface of THIS CAT, the more it begins to resemble The THEORY.

ANOMALY #4:  HIV-infected patients who are placed on immunosuppressive therapy, and then have that therapy withdrawn, have been known to exhibit a rebound in T-cell counts to ABOVE the level they were at before the suppressive therapy was administered.  Why?

If currently accepted theories are correct, and the immune system is only just barely losing the war against HIV, then suppressing immune function ought to have an additive effect on the course of the disease. (That is: clinical decline in the patient ought to be accelerated.)  I am aware of no explanation that The CAT offers to reveal how lost T-cells would be replaced under such conditions, let alone result in a net gain in numbers of cells.

But, if inhibiting the immunological inflammatory responses resulted in the attraction and absorption of fewer cells into syncytia, then CD-4 counts might actually rise following the withdrawal of the immunosuppressive therapy. (The therapy itself might likely lower T-cell counts while it is underway.)  This idea implies that cell ABSORPTION accounts for the critical decline in T-cell counts.

Hmmm... there's that "syncytia" thing, again.

The point I'd like to make here is that, if syncytia figure prominently in the clinical decline of the patient, then the explanation that declining T-cell counts are due to the FAILURE of cells to die becomes much more plausible.  This would lead to the "companion" conclusion that dying cells are being replaced, probably by sending some sort of replacement signal to the body.

It should be noted that the above postulates are based on my observation of patients, not on laboratory experiments using test tubes, microscopes, flow cytometry or the like.  It would be nice to have some sort of experimental evidence to help prove or disprove the premise of The THEORY.   But how could we devise such a test?


A DISCLAIMER FROM STEVE SCHALCHLIN: Dickie is my friend in Los Angeles who was infected with HIV in 1981. He's been through more near death experiences than anyone I know, including a recent two month delirium where his liver was failing and he was dying. But through a careful balance of some drugs that alternatively dehydrate and then rehydrate him, he is alive yet again. 

Dickie, after he got sick, began reading books on microbiology. And when we met earlier this year, he used to sit for hours and just explain for me microbiology and all the sites on the cells and what proteins do, etc. He kept telling me about his theory about the immune system. He had it well thought out and, as far as he could tell, it -- THE THEORY -- can account for all the phenomena that has occurred so far in the strange tale of HIV. 

This does not mean he is right. His theory is untested. It is ONLY theory. It came to him as he read book after book on microbiology, so it could be a naive theory or it could be one of a billion theories. So why have I invited him to be a Bonus Round site? 

Because when he's hot on the trail of new information and when ideas are popping in his head; when he's making new discoveries through the books and published studies, I see him come back to life the same way Jimmy saw my songs bringing me back to life. 

There are scientists who read my page, you know. Even if his theory doesn't pan out, I will learn a lot about my own body and about the thing that almost killed me. (cue song: "at least i know what's killing me"). 

Dickie is not a doctor nor does he work in the medical field. 

He's a Patient. *cue the mannix theme* 

So, the reader should note that THIS IS ONLY A THEORY we are using as a jumping off point to ask questions and learn more about HIV and the immune system. 


Tell us what you think. -- The Bonus Round Management. :-) 


© 1998 by Richard Remley (deceased)


| A Brief History of the THEORY  | The NICKEL Tour  | The DIME Tour |
| The FULL MONTY - Chapter 1 | The FULL MONTY - Chapter 2 | The FULL MONTY - Chapter 3 |
| January 1999 - New Research Supports The THEORY |