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CD4 and CD4/CD8 ratio
Oct 26, 2002

Dear Cal, I have been recently diagnosed HIV+ (June 02) and have some questions regarding both the CD4/CD8 ratio and CD4 which do not seem to be spoken about as much as the CD4 absolute. My first question is what exactly are CD8 cells? What happens to them with HIV infection? My understanding is that they increase - is this correct and if so when in the course of infection (after how long)does this happen? Secondly what is the meaning/significance of the CD4/CD8 ratio? My doctor said that with HIV infection this declines/inverts - without meds what level does this ratio fall to and again when does this happen (immediately after infection or after a few months, a year??) Final question is re the CD4.How quickly does this fall on average per year without meds? What is the range? What weight do you place on the when someone has a >35 but a low CD4 because of a low WBC? Would you still start meds if the CD4 went below 350?

Thanks in advance for your response and for the great service you do - your work has certianly made the shock of HIV infection easier to deal with

Jim

Response from Dr. Cohen

Thanks Jim - glad this helps.

So - about these cell counts. We simplify the immune system to make it easier to count and report things. And one important simplification is this one - we can distinguish two major types of important cells in the immune system called lymphocytes - some that are helpers (CD4) and some that are suppressors (CD8). And in general, of these two types, HIV attacks CD4 cells, and sadly our cells typically lose this battle over time, depleting the ranks. How fast that happens depends on two factors - one is how good our immune response is at controlling HIV, and secondly, how nasty is the strain of HIV someone acquired. That balance of these two forces results in an HIV viral load measurement - and that viral load fairly well characterizes how fast the Cd4 cells will fall - the higher the viral load is, the faster the cells fall. So, as I recall from the studies done of this years ago, if the viral load was about 10-30 thousand, we'd expect about a 30-40 cells loss on average per year, but if the viral load were higher, the cell loss is of course faster. But even within these averages there's plenty room for individual differences - so the exact numbers aren't all that useful except as broad guidance.

Now - there are these Cd8 cells. And it is true - as the Cd4 counts fall, the ratio of dividing CD4 by Cd8 will result in a lower number since the top number drops. And when we treat we grow Cd4 cells, and so the number heads back to above 1, which is what we see in those without HIV infection.

The problem here is that this is a crude test. There are many many types of Cd8 cells - and so summarizing this count by that one marker isn't all that helpful to us in our monitoring. Most studies focus on the Cd4 counts since this count does predict pretty well who is at risk of illness - but it is far less clear what benefits there are in understanding the damage of HIV when looking at the Cd8 counts in addition. So personally I don't do much with the CD8s nor do I divide one by the other for any monitoring... and it is not clear what added benefit there is in doing so.

As for the CD4 count versus percent -- you are right - someone can have a good cd4 percent, but if the overall number of cells is low - the count will be lower than average given the percent you see. The hard question is which value is more predictive of the risk of illness? While there has not been a lot on this that I know of, our group did look at this many years ago and found that the lower of these values, when they disagreed, was more predictive of risk. Meaning if the count is low, then you might base decisions on that value rather than take comfort in the higher percent.

So - if that is so - and someone -- you perhaps -- has a count of 350 with a cd4 percent greater than 35% - what to do? Well - that's an easy one. We don't know the right answer. We don't know what the best answer for that one is still, after all these years of research...

Here is what we do know. At either percent or count you mention, the risk of illness due to HIV is very low. And while you don't mention the viral load here - with these counts, the risk of illness should be low for the next year even without any treatment. Which is why the guidelines written about when to start all suggest that the time to start is somewhere above a count of 200 CD4 cells, but we don't know how high above 200 to recommend. And that's because treatment has good news but side effects and resistance can and do also occur. So there is still this balance to consider in when to begin.

And one recently launched trial is taking that to the next step - which is that the timing of starting is not one that is made just once - but can be made again and again, since if someone does delay starting meds at higher CD4 counts, then once on treatment the cell counts should rise again to levels at which someone didn't initially want or need to be on meds - and so there is the option of not only when to start, but when to stop that can be considered. A very large study (the SMART study) has been launched in several countries to address this directly, and is another consideration for you. As for this big question, you can await the answer from this or other trials like it, or perhaps be a part of a study designed to answer this question.

Much to consider. But for now, I wouldn't worry too much about dividing cell counts...



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