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tenofovir - what to add
Aug 6, 2001

Hello I think I asked this question before, but I will try again. I am a very experienced med taker. I have run though all the available drugs -- with the exception of Kaletra and agenerase. My Dr is trying to get me enrolled in a program for tenofovir. My question is what should I combine it with. Is the tenofovir and kaletra combo potent enough to work. Should I also add the agenerase???? I have been on therapy for 8 years. My cd4 just dropped to 140 and my viral load went to 120,000.

Response from Dr. Cohen

This circumstance is a pretty common one and so here are the issues you face.

First, it is worth thinking about why these meds haven't worked well for you in the past. There are many reasons - we have made mistakes in how we have used these meds in the past and this has led to much resistance. One factor that also emerges is the issue of adherence to the regimen, as we have seen so much evidence to suggest that erratic missing of some doses now and then can threaten some of these regimens. So as you consider your next step, it is worth ensuring that whatever was not done in all prior combos be done better in the next one...

As for your next step, here are the issues. You don't mention whether a resistance test was available to help plan this next step. If you are now on meds, and getting ready to plan for a switch, this may be a good time to get one. Since whatever meds you can use next that may be "active" is worth knowning about. Since even the three you mention, Kaletra, Agenerase, and Tenofovir may or may not be potent enough for you.

How can we tell? Well, again a resistance test can be somewhat helpful. For example, we have seen info to suggest that the more resistance you have on these tests, the less likely it is you'll respond. There are tests called genotypes, phenotypes, and one called a virtual phenotype. And there are some guidelines for some meds, such as Kaletra to help give you some idea of how likely it is that drug will work for you based on the resistance test. One chart to help interpret the test for Kaletra is available, and is a part of the text called the "package insert", the very tiny print that comes in every box of medication in the US. In there you'll see that some will, but others won't likely have much activity when using Kaletra, based on how much resistance was created by other protease inhibitors. And so a resistance test may point you to whichever meds still have at least some chance of working - since taking just three new meds may not be enough, whereas taking five meds might be more effective. But it helps to know which five, if that is the direction you take.

And it may be that whatever meds you take do the job - either all the way to an undetectable viral load - or just part of the way down. And if that is best we can do, it appears likely this is still worth doing - since even partial control can get you a CD4 boost. But in time if it is still growing while on meds, this virus wiggles out from under - so we always are on the lookout for ways to go for maximal control - so as to get the longest benefit we can.

Now, in the absence of a resistance test from you, and based on many studies, using Kaletra and Agenerase often appear to be the best options left, since they do appear on studies using resistance tests to retain activity after other PIs were used. And as a result, many clinicians have put these two agents together. But another issue that is a recent concern is what dose to use of these two meds when using them together - since there are studies ongoing to try and help define what the best dose of each should be. And we don't know yet. So while we can guess, another option, available in select areas, might be a test of drug levels. These tests can sometimes help guide us in changing a dose of meds that you are on to either increase them so as to get all you can from them (or less likely in your case, decrease the dose to avoid unnecessary toxicity). For example, while the standard dose of Kaletra is three caps twice a day, perhaps you would do better if you were on four caps twice a day. And so on. These tests are still considered "experimental" and controversial at best but are another consideration.

One more point. You don't mention your history of CD4 counts and viral load. If your CD4 count now is near the lowest it has ever been, another option to consider is one being studied across the US, which is to test the role of interrupting treatment before switching to a new combo. There are a few hints from prior studies to suggest that for those with a lot of resistance, stopping meds may allow the resistant strains to fade away a bit, and this may be just enough to increase the odds of the next combo working better. We don't know if this helps or not which is why it is being done in clinical studies - to do it safely with intensive monitoring, and in so doing, learn in a definitive way whether this added step helps. Since, for those in this circumstance, any little bit may help. And as we don't yet know if this interruption helps - the studies continue.

Your next step is key - we only have a few options now, and while the industry is working on the next steps for you and others in this circumstance, it will be awhile before a lot of meds get here. So anything you can do to make this work is worth considering.

Hope that helps.



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