|1st Major Regime Change in 6 yrs
Oct 12, 2003
I was diagnosed mid-Sept'97 with VL 900,000 & T4 Cells less than 75. Hospitalized with PCP early Oct'97. Began HAART Oct'97 (Fortovase, Viracept, AZT and Zerit). Excellent results. By Jan'98 VL undetectable w/ T4 cells rebounding to low 300's. Persistent neuropathy of feet so switched from AZT/Zerit to Combivir in '98. Subsequent MRI of spine revealed micro lesion of spinal column-probably from primary infection. VL continued undetectable through late'00 then began occassional quarterly blips of(400-650 copies)followed by undetectable. Quarterly VL detection(500-800 copies) emerged in'02 so switched from Combivir to Trizixir. T4 cells currently 550. Have tried several times to get geno/phenotyping but not enough virus copies for a complete test.
My ID physician has suggested three potential tx options: a) no change - monitor VL, b) Sustiva QD w/ Trizivir BID, c) Sustiva QD, VidexEC QD, Rayatax BID, Norvir QD.
I would appreciate your opinion on these options and treatment recommendations. Thank you for your assistance.
Response from Dr. Cohen
Sure thing. First I just want to take this opportunity to point out what we've learned not to do anymore since we can do better. For example, we have learned that the combination of AZT and Zerit (d4T) is now strongly discouraged since we have learned that this combination does not perform as well as other NRTI pairs, including the Combivir that you later changed to. Similarly, we have done work over the years to try and improve upon what was an initially interesting protease combination using Viracept plus fortovase as you are on. And based on recent data, we do find that we can make this simpler and probably more potent for example, using what we call "boosted" protease inhibitors instead of the double PI approach you list here. Examples of boosted PIs include Kaletra, or most any of the others when we add a low dose of norvir (ritonavir) to them.
So one detail that I will guess is that since going from Combivir to Trizivir your viral load has stayed suppressed to <50. I note that you tried to get a resistance test done during some of the low level viremia events but could not get the result successfully so we will just have to guess what resistance your virus might have. And if there is any underlying resistance, the most common mutation is the M184V mutation, conferring resistance to the 3TC that is one of the antivirals in both of the combination tablets Combivir and Trizivir.
So, now what?
It is not clear why you are asking about switching if this is motivated by ongoing viral load "blips" or just trying to find a more "compact" regimen that is easier to take. Both reasons are good ones and both might lead us to similar places, with the exception of your choice "a" of not changing at all since you can stay on this based on what you have written here unless this one is just too much - and you need to change this and see how we can do better. For example your regimen is probably about 12 pills twice a day although Viracept recently was reformulated so that instead of taking five tablets twice daily, you can take just 2 twice a day. But this is still a higher pill burden than the other combinations listed -- indeed it is one of the highest of most regimens we use these days...
The first switch option you mention is simply exchanging the protease inhibitors for Sustiva one of the most potent drugs we have in the class of drugs called nonnucleosides. Sustiva-based combinations have been among the most consistently successful we have with some of the best responses over time. And this new regimen would be very "compact" in that it would be only three tablets per day. The only potential reluctance one might have in switching to this one is that the Trizivir may not be fully potent since there is some reason to suspect resistance to at least the 3TC, and perhaps even to one of the other antivirals contained in the Trizivir. And since we can't know this based on your history it is hard to know if this revised combination will be amply potent or if it might be less that fully suppressive. And there is some concern that since Sustiva while potent only requires one mutation in HIV to create high-level resistance there is a desire to use it as much as possible in a maximally potent combination and not allow HIV to develop that one mutation.
And your next combination is an example of how we might create a more potent regimen. Your combination #2 is an example of using the newest protease inhibitor called atazanavir or Reyataz. While this protease inhibitor is itself potent it can be made even more potent by using 300 mg of the Reyataz and then adding a low dosage of norvir (ritonavir) -- specifically adding 100 mg to this. The addition of ritonavir acts to increase the blood levels of atazanavir/reyataz and this make the protease inhibitor far more potent. It also allows us to use it with Sustiva since this drug can lower the blood levels of the atazanavir. And this becomes a very potent combination since you are combining the already potent drug Sustiva with the highly active single boosted PI. And then your clinician suggests adding ddI to this in addition which certainly only adds more potency and this is reasonable to do although there is some reason to predict that just the combination of Sustiva and boosted atazanavir might be enough just by themselves.
One comment however is that the atazanavir boosting works best when you take all of the atazanavir at the same time as the norvir so the only modification I'd suggest is that you not take the Reyataz twice a day as you describe (BID means twice a day for those that don't know) but take this all once a day at the same time as the norvir. Indeed this entire combination might be dosed all together once daily though technically the Videx EC is still recommended to be taken without food, while Reyataz should be taken with food. There fortunately is some debate about how important this food restriction is for Videx some clinicians do use Videx EC in combinations that are otherwise taken with food given that the food impact on this formulation is small. Also - note that there are certainly some possible side effects seen in those starting any of these drugs those are another aspect to how you might choose which way to go next.
In sum any of the options you mention are reasonable to consider. And there are of course many many other options in addition to the three you list here. However either of the newer combinations offer you a far more compact regimen with fewer pills and an easy schedule the second combination even taken just once daily. And both of these alternatives should work with the second one adding even more insurance by starting both a boosted PI and a nonnucleoside to maintain control. Hopefully this is of some help in sorting through your next step since it is possible that this next change may allow a very durable response that could last for years to come.
ACTG 5095 - keep Trizivir alone for VL suppressed patients ?
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