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I need a new drug!
Jul 20, 2002

Dear Dr. Cohen,

I have been hiv+ since 1997. I started HARRT immediately. I have been on a holiday now for about 4 mos. since finding out i have drug resistance to many drugs. I tried to restart with DDI, Tenofovir, and Ziagen. I could not tolerate the Ziagen, it made extremely ill. My Dr. suggested to wait until mid July when a new, no side-effect, once a day PI will be out. I will continue with DDI, Tenofovir, and this new PI. What is this PI? Is this combo a good choice? My last labs were VL=60,000 and CD4=roughly 700. I have also heard that epivir can still be used in certain combos inspite of resistance patterns. Is this true? I am resistant to all sustiva class of meds, epivir. What is your pick of drugs for me? Thank-You in Denver.

Response from Dr. Cohen

Hey Denver. While I can't pick drugs for you, since I don't have all the info I'd need to do it right, I can offer some considerations.

One is to start at the beginning of the story - which is the need to treat. With a CD4 count of roughly 700, there is no clear reason to restart on antivirals at all (unless roughly includes a cd4 count below 200). Even with a viral load of 60 thou - your Cd4 count should stay well over 500 for at least a year if not longer off antivirals. Especially given that you state you have gone through most if not all available meds and have few good options now. And so instead of using up each med as soon as it gets here, it may be safer for you to take advantage of your good counts, postponing treatment a while, letting the pipeline fill up a bit, so your next combo will have a better chance of working for you. The more active meds you start next time the better, and that means starting more than one. And if I understand it correctly, you are talking about adding just one new one. So one approach would be to hold off for a while, perhaps on no meds at all so you don't create more drug resistance to these and future meds. One alternative is instead to go on a combination of current meds, rather than always adding the latest and not getting what you need which is effective control so you don't have rebound on it and then need the next one and the next and then the next due to inadequate control with whatever you've done. And while ddI, tenofovir and the next PI might work, I'd be concerned it may not. So that is one piece of the puzzle for you to consider.

As for what the new once a day PI would be - there are two coming. I am not sure if either can be labeled as having NO side effects - but more likely your MD refers to atazanavir, the PI being developed by Bristol Myers. There are several good aspects to it, but its role as a "salvage" PI (meaning its activity after significant PI resistance has already happened) is not yet a clearly proven role for this drug. There is also another PI coming - called 908 - but this is just an improved formulation of the PI currently available and called agenerase (amprenavir). It might be active after other PI resistance has occured, but again, no single drug change is likely to be enough...

And yes, epivir (3TC) can be useful despite resistance - in that it is one of the antivirals that has ongoing activity even despite resistance. This activity may be about a half log, and may not last forever if there is ongoing viral growth... so isn't enough on its own. But certainly can contribute to a new combo when that time comes.

Now, there is a pipeline coming with meds designed to be active despite resistance to the current ones. For example there is a PI called tipranavir which shows promise after multiple PI resistance. A new class of antivirals can also be of use here and the first to gain approval should be T20, the first entry inhibitor to get through phase III testing. Behind these there are a few others as well... and so the longer you can postpone, the more we'd have to play. And the more fresh potent cards in the deck, the more likely it can work to control your HIV. And the less you'll need to hope for the next...

Hope that helps.



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