Topping up trizivir
Oct 18, 2003
I've been on trizivir for about 15 months now, with mixed results. For the first few months it worked fine: v/l was <50 (it was 100,000 when I started after a 15 month break), T-4 climbed from 200 to 460. But after about 6 months things weren't so great: v/l went to 250, then back to <50 and now back up to 226. T-4 remaining stable at around 460.
It's obviously time to change things. My doctor wants me to add a new drug, but I've had terrible experiences with Sustiva so that's out of the question. What would be the next best addition to the trizivir regime? Do you think it makes sense to have a resistance test?
I'm now talking a break from all medications, so would this be a good time to look at a completely new combination?
Thanks for all your help.
Response from Dr. Cohen
So, Mark, you've raised a coupla options. First one now that you are off meds when to restart? And then of course, with what do you restart?
Let's take the first one. Short answer as long as the CD4 count is above 200 our current info suggests anytime above 200 is reasonable. There are strong opinions based on our observations and convictions about how high above 200 we recommend someone to start. And, if all is said and done, when / if we ever get the perfect HIV treatment this will be a much easier debate. Since much of the back and forth about waiting versus starting/restarting comes down to a battle between the side effects of untreated HIV which are numerous and real (so start treatment as soon as you're willing) to the side effects and "burdens" of pill-taking to control HIV including distressing body shape changes, mood alterations (perhaps your Sustiva-story?) and so on. Not to mention the risks of resistance and challenging questions about what to do about them But - If treating HIV were a vaccine that we gave once every 3 months this paragraph would have been quite a bit shorter. But it isn't yet. So there is a very large study underway going on around the world at this point called the SMART trial. It compares those who go on and stay on meds if the CD4 count is above 350 versus an alternative strategy of waiting until 250 treating to get the CD4 counts above 350 again and then stopping, monitoring to see when it's necessary to restart meds. And since several studies of both strategies have been done many times we know we can do either. What we don't know is in the long run which is better. Thus the study. So for those open to helping answer the question you might check out the Web Site and see if there is a Study site near you. (click on the text at the end of this answer to go there...)
Now what to restart on. Since I don't know your history of what else you've taken it is harder to answer this one well. Clearly you tried and didn't tolerate Sustiva I'll need to assume that is the entire list of meds you tried so far. Which leaves us a lotta options. What we have learned is similar to what you've noted which is that while Trizivir can be used it is not as potent as other options. And for those with viral load above 100,000 when off meds we need a potent combo. And so we'd want to do better than Triz. And since based on those viral load "blips" you report we also should assume there might be some viral genetic resistance to at least one of the drugs in Trizivir which usually is something called the M184V mutation conferring some loss of potency to the epivir that is one of the antivirals in the trio-pill. So then what is more potent that Triz and retains activity despite that M184V? And avoids restarting Sustiva?
Among our best studied next steps are regimens built on "boosted" PIs. This simply means a protease inhibitor that is "boosted" in potency by the addition of a low dose of norvir/ritonavir. This acts to increase the blood level of the PI and this allows the drug to be far more potent. This increase in the potency allows it to be reliable for those with a viral load of 100 thou or greater as well as handle the fact that the other meds you might add to the PI may have some diminished potency from whatever mutations arose on the Triz. And since you are now off all meds a resistance test is sadly unlikely to tell us much. Since the "wild type" HIV is still there as well - and is often able to grow so well when off meds that it obscures our ability to measure what additional resistant strains might be swimming in the soup. And so while you can get the test odds are good it won't contribute much to informing the next step. But some might still check just realize that it may not tell us what we want to know.
Which boosted PI? Well it is fair to state that assuming you're nave to the PI family all of them want to be your first friend. Since all of them can do well in this role as first PI. There are several boost-able PIs that can be selected these days including Kaletra, Reyataz, and Invirase. There are also two PIs that can also be listed but are less typically selected -- at least in studies done here in the US - indinavir and amprenavir. Soon amprenavir will be released in an all improved reformulation called 908 at least so far and at that point it can be added to the former list. Which of these to choose is a far longer answer and something you and your provider will need to discuss assuming you choose from any of these.
As you'll also need to discuss what meds to add to it. Since the choices of combinations based on your favorite boosted PI are quite variable. Anything from restarting the Triz to using some of the meds within the Triz and/or using others in the same family as Trizivir that you've not yet taken like videx or Viread or even just dual PI combinations combining two boosted PIs together which has done very well in studies... or even the provocative and still highly controversial approach taken by two physicians in the Southern US who've presented data on the use of only one boosted PI in their studies just starting Kaletra.
So you've got choices. About when to restart. And on what. And hopefully this helps give a framework to your next steps. Let us know what happens.
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