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time to change?

Apr 24, 2000

Dear Dr. Cohen,

thank you for your forum and help you give out. I have received my latest lab results. T-cells, 650 and %is 34%. Viral load, now detectable at 850 copies, three months ago <50, t-cells 653 with the % at 34%.. I started triple combo drug therapy May 1997 with viracept,azt, 3tc,fortavase HC. T-cells were over 500 and Viral load was very low at 387 copies, off all drug therapy for 8 months just prior to commencing the combo in May 1997.(I had no medical care for 8 months)

Over time the combo changed to: Viracept, combivir and fortavase SC. I have had some viral load blips the last 8 months but everytime VL was detectable(very low levels 54-254 copies), the next test VL was undetectable.

Also I have missed some doses of the drugs but not many. I have also started IL-2 cycles approx. 1 year ago,every other month. My t-cells jumped up to 1000 and stayed very close to that number until three months ago. T-cells have bounced while cyclying IL-2: 1300,1000,1200,800,753,653.650 now.

Geno type testing shows strong resistance to AZT & 3tc.

Before starting triple therapy I had used single nrti's before 1996.(d4t & ddc& azt)) I have been positive since 1987.

So, Feeling great, no problems, except detectable VL now.

What do you think I should do? Change drugs regiment? Wait some time then repeat another round of tests? Wait for newer drugs- abbott's protease & sustiva & DDI?

I don't know how to proceed? Thank you for your response.


Response from Dr. Cohen

Well, kyle, a few options to consider...

As you point out, you have a very good combination waiting for you that should work well in the future - another PI plus a nonnuke such as Sustiva, and you could enhance that with ddI (altho some of the high level AZT mutations might decrease the potency from other NRTI's including ddI). And newer meds coming like tenofovir to boost the potency as well. So one principle to what you do now is to both stay well, and use the meds in a way that does not damage the success you would have from the next combo.

It does some sense for you to be on a double PI combo now since the nukes (azt/3tc) may be contributing only a little of the potency of your current combo. And 2 PI's are more potent that one. Which two to pick is an ongoing debate - and it does seem that, if we believe your viral load results, the two you are on now are not fully suppressive for you. In general, low level viral load "blips" don't seem to lead to resistance to the PI's - 3tc is the most vulnerable drug to resistance in this combination. And you mention you have resistance to it now. But higher level rebounds could cause more PI resistance, and the concern is that the more resistance you have to these, the less you'll respond to others. However, you mention abt-378, and it does seem to be fully potent even after other PI's are lost to resistance, so that is the card in the pocket for you.

So - a few options with these principles. One is leave it alone - working well, you feel well, and only low level resistance on a combo that allows you future options. Second, intensify this regimen. You can change to two other PI's - we think for example that ritonavir plus a second PI - Crixivan, Fortovase, Agenerase - all might be more potent because we can get higher blood levels of the second PI this way. And higher blood levels is more potent. Or switch around the nukes - stop azt, add either ddI or abacavir. (You could keep the azt, but with hi level resistance, it may be doing less for you, and there is merit to keeping your combo to four and not five meds...) More potent meds might get your VL consistently below detectable, and this postpones resistance that much more... so a more durable combo.

Now for the controversial option... Third - with your T4 count - there is debate whether you even need to be on antivirals - with a T4 count over 500, and we don't know your viral load off meds do we? So, instead of risking resistance while on meds at a healthy t4, some are stopping meds, decreasing risk of resistance to the meds, and if the t4's drop to some lower number, restart later, with this or some other combo.

There are variations on these themes - but that is the current thinking. Which way to go? We truly don't know the best way to go here - which is why there is discussion of a clinical study of exactly this situation, comparing some of the above options. Because each way there are pros and cons...

good luck. let us know what happens.

What are the signs and symptoms of cytomegalovirus?
quite happy with my cocktail results!

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