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Rapid cd4 drop--time to restart meds?
May 5, 2003

Dr. Cal, I became infected in 1999. I began treatment during acute infection, my VL was 4.5 million and the CD4 was 428 26 percent. I have been off meds since August of 2001. When I stopped I was undetectable and had a CD4 of 786 33percent. My last five labs:

2002 Feb 20: VL 11K CD4 605 24 percent Jun 24: 28K 586 23 Oct 1: 26K 531 21

2003 Jan 7: 24K 486 21 April 14: 34K 369 25

First, what do you think of this rapid drop--is there reason for concern? It's particularly distressing to see my CD4 drop below the point where it was during acute infection. My doctor wants me to go back on meds permanently. But, Im wondering if I should restart and get my CD4 up in the 700-800 range and then stop again. I wish I could be in the SMART study but it's not available where I live. It will be years before there are any results. Is there any anecdotal evidence now that this works? Thanks.

Response from Dr. Cohen

Thanks for the note. And the details.

So - the first question is back to you - which is what do you mean by "does this work"? And since waiting any longer here for a response from you to clarify is unlikely to be all that productive... let me elaborate on what I mean.

We know that you can start meds during acute infection and there were early data to suggest that at least some will be able to use this to improve their long term outcomes. As you likely know - what happened in a few early studies is that people who did start early - during the acute initial infection with HIV - started meds, and then stopped = and some would have a long period of time with low viral load and stable CD4 counts but others would have higher viral loads and CD4 drops - and so if the immune system could not control HIV well enough during the first stop - they'd restart and after a time stop again. What is found in test tube studies is that there is evidence that these stops/restarts can increase the number of cells directed at HIV itself in some people - and the hope is that these repeat stops/restarts expand the effective cell population to increase the chances that your own immune system can control HIV. And have even more stable counts over time when off meds.

So what do we mean by controlling HIV? This is very ambiguous - it may be that your own start/stop led to improved outcomes compared to what would have happened if you never started meds at all. We simply cannot tell - and studies are gearing up in Boston, Sydney Australia and elsewhere - to address this critical question. Meaning if we do find people who have become HIV positive in the past year - can we boost the immune system to do better with treatment?

So - in your circumstance - your concern is with the CD4 drop to just under 400. And this took about 18 months. Is that fast? Given your viral load - it is perhaps a bit faster than expected - but not out of what we can see when people are off treatment. But yes - when HIV is untreated - with a viral load in this range - losing >100 cells per year is a bit faster than average. However there are some who will drop faster - and the factors that predict this are still being clarified by researchers. But I also do note that your cd4 percent is pretty stable over the past year - and it is not so clear how to interpret this difference in how the counts responded. In any case - what to do now?

One approach is to do what your clinician said - restart meds and stay on from now on. And no doubt your HIV can be controlled, your CD4 counts will improve, and if you find meds you feel well on - this can work... but I think you are asking about more start/stop approaches to further boost your own immune system's ability to control HIV without meds in the future? So as you mention - can you restart - get the counts back up to say 700 - and then stop again?

We truly cannot yet tell you how well that works to "boost" your immune system. There are hints that some - perhaps 25% - seem to improve in their own ability to control HIV with these interventions at least temporarily. This is still a controversy and we are still learning how to do this if it can be done at all... but the short answer is YES you can start meds, and stop at higher counts. That's been done for years - and as you've shown - at a minimum you can have over a year off meds - and might only need a year back on to get the counts high enough so that you can have another year off - even if all this does is boost the T4 counts high enough to give you the cushion that allows you to stop and enjoy the time off without risking HIV related illness...

As you note our SMART study will answer this part of it - can people safely start and restop and just have time off meds - and in the long term is this as good (or better) as staying on every day every year -- but until that is enrolled and done - we are guessing. And so the best we can say for now is that you can start - and you can stop. And there are hints that repeated stops/restarts might reset your viral set point to a lower point and give you even longer time off meds... but this is not certain - and you might have the same time off that just happened. Which is 18 months. And that might be one way to say that your approach "worked".


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