Re: Undetectable VL but t-cells not going up much?

September 19, 2006

Thanks so much to everyone who responded to this situation with their

own experience or information. It confirms some of what I knew, and

helps me to solidify a position that I want to take with my physician.

Sanford

Sanford M. Gross, OD, FAAO

Associate Professor

Illinois College of Optometry

3241 South Michigan Ave

Chicago, Illinois 60616

>>> " Norm Stuart " 09/18/06 8:14 PM >>>

One of the ways HIV affects T cells is that HIV proteins, particularly

gp-120, can inactivate the T cell making it non-responsive to

pathogens.

If you take these T cells out of the body and wash them with saline

solution, these cells will become normally responsive within 24 hours.

So what does this have to do with a low T4 count after controlling

your

HIV viral load?

1.) HIV proteins from degraded virus can still inactivate T cells and

the viral load test does not measure this. So an undetectable viral

load

is likely to imply an improved immune system but not a fully

functional

immune system;

2.) T Regulatory Cells (CD4+/CD25+/FoxP3+) are one of the primary

control mechanisms behind total T4 count.

A.) French and Swedish researchers have found that a culture of blood

from HIV+ people can quickly increase the number of T4 cells if you

kill

all of the T Regulatory cells with a monoclonal antibody to CD25+. The

CD25+ receptor is also called the Interleukin-2 receptor. They

logically

suggest using this killer antibody in patients as a therapy to

normalize

T4 counts in people with HIV. I'd be very interested in the results

but

no amount of money could interest me in being one of the first to try

this therapy.

I expect that killing off all T Regulatory cells would normalize the

T4

count for a period and then the effect would wear off, needing another

infusion of anti-CD25 antibodies. Why? HIV proteins should inactivate

T

Regulatory cells in exactly the same way that they inactivate other

CD4

and CD8 T cells. If you have a viral load, this inactivation takes

about

30 days. If you have an undetectable viral load this inactivation

takes

longer, typically 60 to 90 day. So I expect you would need and

anti-CD25

infusion every 90 days or so.

B.) In contrast, NIH researchers in America have found that

Interleukin-2 injections increase the number of both T Regulatory cell

and T4 cells. How do we explain this seeming conflict with the French

and Swedish results?

I think Interleukin-2 and anti-CD25 antibodies are doing similar

things.

When Interleukin-2 binds to the CD25+ receptor on T cells, it

activates

the cell. Activated cells which are abnormal in any way begin the

apoptosis process in which they kill themselves by allowing in a

influx

of calcium ions which destroys the cell's DNA. So I suspect that

Interleukin-2 injections cause the inactivated T cells to kill

themselves. Interleukin-2 is also a T cell replication signal, so

normal

T cells and T Regulatory cells proliferate and increase in number.

You can see this effect is you take a blood draw and get T cell counts

every day while you inject Interleukin-2. You will observe that during

the first two days of Interleukin-2 injections, your T4 and T8 cell

counts will decline while your T4 and T8 percentages remains constant.

On the third day of Interleukin-2 usage, and on each day after the

Interleukin-2 treatment, your T4 and T8 count will increase. I have

observed the same effect on my T Regulatory cells, with the caveat

that

we only measured CD4+/CD25+ without the FoxP3 marker when we did my T

cell count daily.

So Interleukin-2 injections causes a die-off in some T4, T8 and T

Regulatory cell counts during the first two days of use, and then

produces an increase in T4, T8 and T Regulatory cells over the initial

pre-Interleukin-2 levels. I believe this is due to the apoptosis of

non-functional cells.

So I think Interleukin-2 and the anti-CD25+ antibody increase T cell

count through a similar mechanism. Both kill of non-functional T

Regulatory cells and create new T Regulatory cells which are not yet

rendered non-functional from HIV infection, even though the viral load

is undetectable. But only Interleukin-2 creates this die-off of

non-functional T4 and T8 cells - although the antibody does create new

cells to supplement the inactive cells.

I use 7.33 mu of Interleukin-2 each day for 3 days, every other month.

This is one bottle of Interleukin-2 (Proleukin) every other month.

Always have Indocin-SR available to control fever, if it develops.

The anti-CD25+ antibody has not yet been used in a human and so is not

available, but Proleukin is available at your pharmacy with a

prescription.

If you take antivirals to make your viral load undetectable, it is

certain that some percentage of your T cell count is inactivated T

cells

which provide no immunity. So while a person with a controlled viral

load is almost certain to have an improved immune system, it is also

certain that they don't have a normal immune system. This is

particularly true in the GI system where HIV remains uncontrolled,

even

in people with an " undetectable viral load " . In other words, studies

which measured the HIV viral load in your intestines find it is quite

detectable, in contrast to the blood level.

>

> I have been on Sustiva/3TC/Viread for 9 months now (been poz for 24

years, but that is another story).

>

> The good news is that I went from a pre-treatment VL of 120,000 to

264, to 62 to undetectable in three months and I am still

undetectable.

My t-cells were creeping up from 220 to 340 to 380 to 440, but just

fell

back to 340, despite being undetectable.

>

> My Dr. is not concerned and says that sometimes there can be blips

like this and that really being undetectable is wayyyyyy more

important.

He says some people go undetectable they never get really huge t-cell

increases, but that in his experience, he has never seen anyone with

an

undetectable VL get any kind of HIV-related illness - no matter what

their t-cell count is.

>

> has anyone else experienced this phenomenon and does it mean

anything,

or should I just listen to my Dr. and disregard it?

>

> in Toronto

>

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September 19, 2006