Time for tenofovir?
Mar 25, 2001
Hi I am currently on 3tc/d4t/rit/saq and although failing with viral load of about 20 000 my CD4 has been stable at 400 for 3 years.I have 4 RT mutations and 4 PI mutations (can't remember the numbers)Should I stay on this and risk more mutations or switch now to an NNRTI (never had) with tenofovir and maybe Kaletra?What other options can you recommend?Thanks
Response from Dr. Cohen
This is one of the most challenging questions we face in treatment for HIV. I'll try to show you our thinking about this.
As you point out - the key of the uncertainty is how quickly you might, despite the viral suppression you now have, get even more mutations in the classes of agents you are taking. And the more mutations there are, the more cross resistance we see. And with that, the less the response from the next regimen when using meds in these classes.
This is clearly shown for the newest PI - Kaletra (also spelled Cal-etra by those in the know...). What has been seen is that Kaletra is successful and potent to switch to when there are up to 5 of the common PI mutations. However, the more mutations above this that there are, the less potency you can rely on from Kaletra. So this would push you to change sooner rather than later - avoiding new mutations. Sadly we don't have a good way to predict how quickly new mutations will arise - although it seems a worry at your current viral load.
Now, if you have never taken a nonnucleoside before, adding one to your next regimen is an effective approach to a higher likelihood of suppression. A study done in the past year showed a very high success rate when efavirenz (Sustiva or Stocrin) was combined with Kaletra in those using their NNRTI class for the first time, and was especially successful at a higher than standard dose of 4 capsules twice a day - for those who had fewer than 6 PI mutations. And, just to be safe, it is reasonable to add a third effective agent such as tenofovir, since it retains reasonable potency after other nucleoside resistance is seen. In sum, at the current time, the triple you describe sounds potent enough to do the job.
However, at least for now, those whose CD4 counts are over 100 cannot get access to tenofovir on the current expanded access program. And approval of this drug in the US is not expected before the end of this year. So - what to do now? Stay on this regimen, preserving your CD4 count by this partial control but risk more PI mutations, versus a switch now without using tenofovir, or some other option?
One issue worth knowing is how much potency you are even getting from the current regimen. For example, do you know your viral load off antivirals? Is 20 thousand lower than this would be off meds entirely? That can be one way to figure out how much effectiveness you are getting - and helps decide what to do next as well. For example, if your viral load is in a similar range off these meds, then one option would be to stop these meds and avoid accumulating more PI mutations while awaiting the availability of tenofovir. However, if your viral load were high off meds -the viral load will increase when you stop. And this can cause a CD4 loss - although recent studies suggest the biggest predictor of what would happen to your CD4 count if you did stop meds is your lowest CD4 count in the past. And if it were pretty low in the past - that might argue against stopping now. So one question is what you might be able to do without tenofovir - which mutations do you have in the RT class? And, even more controversy - is there any role for a dual NNRTI regimen here? One added option is to consider a dual PI approach if/when you do switch - since there are data to suggest that sometimes two are better than one. Which one to use in addition to Kaletra is yet another decision...
Much to decide. You clearly need to be working closely with someone familiar with the data to help look at the considerations I have mentioned and make a choice. Since, as you can see - much to consider.
Hope that helps.
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