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It's me...Mr. 908 again....
Sep 29, 2002

Dr Young,

Well good news... I got my latest bloodwork back, and 5 weeks after starting on the trial, my VL has gone from 375,000 to UNDETECTABLE. CD4 from 272 to 588. Gotta feel good about that, right?

I have a two-pronged question:

a) I am hearing with ever increasing frequency, that the use of PI's should be scaled back and be saved for last ditch attempts at controlling HIV. This due to the side effects, quick resistance, etc. As you know, Norvir is part of the study. (I'm not sure if Aggresnase (sp?) is a PI as well..???)

Should I not be on this regimen yet? This is kind of unnerving.

b) Many people that I know who are on HARRT take far more pills than I do. (ex: have a friend who takes 4 norvir 2x a day and god knows what else) Does the fact that I only take ONE of each twice a day reduce the occurance of side effects or long term damage to the body?

I know these may seem like long-winded, sometimes paranoid, often amusing questions but you have emerged as my best source of balanced information in this assault on HIV, and for that, Dr. Young, I owe you. Big. Thank you SO much.

God Bles....

Response from Dr. Young

Thanks for the follow up.

Your lab results look great.

The points that you raise about PIs have definately been circulated, though much of what had driven the discussion was the potency, high pill count and side effect profile of the first generation of protease inhibitors. In general, too, these point refer to unboosted PIs (without Norvir, for example). As you have provided testimony to are the improvements in tolerability and pill burden on 908-- . As for resistance, it is generally thought that resistance is not quick to emerge, particularly with boosting.

The use of lower-dose ritonavir should be associated with fewer side effects and toxicity.

So overall, I don't think that there is any compelling basis for recommending non-nuke-based regimens to newer generation unboosted- and boosted-PIs, though there are definately theoretical differences. Some of these clinical studies are underway. Recently presented data on 908 suggest superior potency to the standard PI comparator, nelfinavir (ICAAC meeting, 2002).

I hope that you find this helpful. Thanks again for your participation in the clinical study. -BY



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