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Dec 26, 2000


i have been on crix+retrovir+epivir for almost a year and some 5months but from undetectable levels i was detectable for the past 4months and my doc suggested resistance test which showed that i have developed resistance to Epivir. now what can be my next good combination? do i need to replace all the three or i an just switch epivir?

thanks a lot in advance.

Response from Dr. Cohen

It is a common observation that when there is initial suppression and viral rebound that is not transiently up but stays up - we see resistance to epivir first. In part this has to do with how "easy" it is for HIV to create higher degrees of resistance to these meds. With epivir, it takes just one mutation to lead to fairly high resistance. It appears to take longer to develop resistance to either the retrovir/AZT, and longer still to see it develop to the Crixivan/indinavir.

So now what? Well, most studies suggest that if this is the only med that was lost to resistance, and the others appear to be fully active, you have many options. But the one we still don't know the answer to is that one you ask about - can you simply just substitute something instead of or in addition to the epivir - and otherwise maintain the cocktail as is. The answer is sadly that we just don't know. We have the general rule that we should add or change more than one drug at a time when there is failure. That is because when we did just one change in this circumstance, we didn't see success as often as when we changed two different meds. So the rule is to make more than one change - to both change for what you can see on the test, and perhaps what we don't see but could be there anyway.

However, a series of studies were done when just one change was made. The one done the most was to add the medication abacavir/ziagen to these combinations. And if the viral load was on the lower side, like below 2000 or so, then we could reestablish viral control more than half the time. And the lower the viral load is, the more likely the success. So this is an option. What is quite unclear is whether to continue the epivir despite the resistance seen to it - or stop it. I would guess that most would continue it especially if just adding one drug - but this has never been adequately studied to know the right answer. This approach - of adding just one drug if the viral load is up to a low level - is called intensification - something studied for the past few years. Other meds can be considered here as well instead of ziagen - mainly ddI would be considered.

But is there a second change you might also make here? In part, given that you mention you are on just indinavir/Crix, there is another change that could be made to not only increase the potency of the combo, but also could make it much easier to take. It is difficult for some to take indinavir - every 8 hours, without food. And a missed dose can be what led to the viral escape. Fortunately, we have much research that shows that when we add a second PI called ritonavir/norvir, we can turn Crixivan into a much easier med. Taken then just twice a day, with food. There are two strategies of how to do this change - one that uses two Crix capsules twice a day with one Norvir twice a day, and the other that uses one Crixivan twice a day with four Norvir caps. There is an ongoing debate of which is better - and one that you and your clinician can discuss to see which might be the better one for you. However, both should work well, whichever you pick. And, in one study of people in your circumstance, just this change was made - without initially changing the nucleoside meds first. And it did work well to many (although not all) - but it is another way to approach this. And you can change the nucleosides if your viral load is not below 50 in the next few measurements if this change isn't enough.

So while you might just make one med adjustment - to the nucleosides, making one to the PI side, or perhaps to both, might be worthwhile here - even if we don't see resistance to the PIs. The PI change not only simplifies the combo for you, but turns it into one that is even more potent. And simplicity is one key to long term success.

Hope that helps.


Cal Cohen, M.D., M.S.

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