CD4/CD8 ratio significance?

[friskyguy]

hi all,

Just wondering do many of you out there (on meds and not on meds) also obtain your CD4/CD8 ratio result as part of your periodical labs?

If so what is your ratio?

Does your doctor/specialist talk about the ratio much when you consult with him/her? For me no!

Reason I ask is that there is some thought circulating in studies that;
-maintaining a normal CD4/CD8 ratio > 1 is very important in keeping your immune system strong and operating normally,
-maintaining a low viral load or UD,
suggests that the hiv infected has smaller viral reservoirs and thus perhaps being in the better health position when a potential cure may come along for the eradication of these viral reservoirs.

thanks

[eric48]

The obvious is that inverted ratio is a hallmark of that infection. Other conditions (reanal failure, some cancers, ...) can also lead to an inverted ratio

When a CD4 signals itself as 'infected' it can either commit suicide or be killed by the immune specialized cells, obviously not by other CD4 therefore by CD8s.
The 'extra' amount of CD8 are HIV specific.

As long as a sufficient number of CD4 are signaling themselves as infected, then the humoral response is to expand the number of HIV specific CD8

The same with some other chronic (non lethal) infections such as CMV.

If CD4 are 'silenced' then the response goes down.

The inverted ratio (because of HIV or other) is suspected to contribute to some kind of immuno aging.

This is still open for the jury, since there are some evidence of this 'aging'. nonetheless this 'aging' takes effect well after some other age associated condition develop (hypertension, heart or coronary disease, etc)
In other word, in the non infected population most people will die way before this effect can be of statistical relevance

The debate about this among scientist is quite hot since there are also some strong evidence that this immuno aging' is very very marginal too.

Low VL indicates that viral replication has been 'silenced', at least in clinical terms, which means the person is not at risk anymore.
CD4/CD8 ratio back to normal indicates that infected CD4 are in silent mode. The immunologic system can't hear them much...

There can be several explanations:
1- infected CD4 are silenced (for example if the virus has been able to infect a cell but not to integrate DNA, for example in case of use of integration inhibitors such as RAL)
2- infected CD4s are in a very, very limited number (hence a possible relation to a low infected CD4 cell pool)
3- the immune system is just getting used to the presence of the infection and does not react to the presence of 'signaling' CD4 (at least, this Pr. siliciano explanation for difficulties in eradicating the reservoir in heavily treated patients)

Not 100% scientifically bullet proof , but graphic enough to help understand

or, so I hope

Eric

PS: there is no clinical evidence that there is a difference in life expectancy between people with ration below 1 or over 1, so do not sweat it too much

[eric48]

From memory, the canadian cohort shows that the people with VL < 50 , CD4 > 500 (which are 2 majors health markers)  AND have a ratio > 1 ( a non-major maker) is 7% of treated HIVers

Of note, in the general population a normal ratio is to be within a range of 1 to 4

The 'normal' ratio for a CMV positive HIV neg person is >1
about 98% of HIV + are also CMV +
BUT  The 'normal' ratio for a CMV neg / HIV neg person is > 2  (and age depending)

Hope this helps

Eric
 

[buginme2]

hi all,

Just wondering do many of you out there (on meds and not on meds) also obtain your CD4/CD8 ratio result as part of your periodical labs?

If so what is your ratio?

Does your doctor/specialist talk about the ratio much when you consult with him/her? For me no!

Yes, each time I get a cd4 count done they also return a cd4 percentage and ratio.

My last ratio was 1.1 (I think, could have been 1.2)

Mr dr doesn't discuss cd4 counts much.  We spend way more time going over the complete CBC results and kidney and liver functions.

From my understanding a ratio of less than 1 shows there is a heightened level of inflammation. 

[friskyguy]

Thanks Eric for your detailed explanation and to Bug2 for his reply.

Yes makes perfect sense.

Just a follow-up question for Eric......and this relates to type of med used.

You mention that infected CD4 are silenced (for example if the virus has been able to infect a cell but not to integrate DNA, for example in case of use of integration inhibitors such as RAL)

So would it not be best for the body to be on at least one med that prevents infection of a cell in the first instance?..... such as CCR5 inhibitors as their function inhibits viral infection before it enters the cell at the point of attachment, ie Maviroc (Selzentry).

Would not preserving your cells, be it CD4 cells or monocytes etc from HIV entering in the cells in the first instance?.......understand that other meds allow HIV to infect cells but not integrate DNA therefore preventing replication of HIV. Not sure if I'm making sense? 

[eric48]

So would it not be best for the body to be on at least one med that prevents infection of a cell in the first instance?..... such as CCR5 inhibitors as their function inhibits viral infection before it enters the cell at the point of attachment, ie Maviroc (Selzentry).

At first look, it sems an attractive straegy (I did take the CCR5 test myself...)

Yes, there are limitations
A- the virus must be CCR5 tropic and NO minor  X4 tropic population, so that excludes a number of patients
B - expensive
C- twice daily

but more...
1- penetration in all of your body compartment is a matter of consideration since this is a larger molecule
2- the virus can replicate even without virion entry, because:
 A - one infected CD4 that splits into 2 gives 2  infected CD4
 B - Alex Segal has 'demonstrated' cell-to-cell bridges where HIV materiel is transfered from one infected cell to a non infected cell without the help of a virion...

Intensification by Maraviroc has, thus far, not been convincing.

It is a med that works and some people here use it, but, may be not as far as far as being a reservoir reduction strategy... 

Hope this helps Eric
(who finally even declined the maraviroc intensification)