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Another early treatment question
May 29, 2003

Dr. Young,

You and Dr. Wohl are easily two of the best contributors to this sight. You seem to care a great deal.

Anyway, I've become familiar with the dilemna that has developed regarding identifying acute infections(Immune system preservtion/VL suppression VS. waiting/avoiding early resistance).

I fall in that category, and I only have a short period of time before benefits of treatment will be lost forever.

My question involves the development of new drugs. I will put them into 2 categories: Next generation same target(PIs, NNRTIs, NRTIs) and new targets.

Ok, I'm wondering if you think someone who starts now to preserve immune function could be making the same mistake as in the late 1980s using mono and dual therapies. Will resistance to say, Indinavir create cross-resistance to all next generation PIs? And are the new target drugs going to be used in conjnction with current ones, rendring 'treatment failure' patients hopeless upon their approval?

Should I weigh these factors in making my decision to begin treatment?

Lastly, what do you think of Viread, Epivir, and Viramune for a young, otherwise healthy male in the acute stage who wants to avoid all the telltale signs of the disease, now and in the long term. Can you thik of a better regimin?

Your optimism is contagious, thanks for any info you can add.

Response from Dr. Young

Thank you for your questions and comments.

The key issue about starting early, so far as current data goes, is starting during acute infection-- this means prior to full antibody conversion and typically within the first 12 weeks of initial infection. After this period, the benefits of early initiation of treatment becomes much more controversial.

Provided that the regimen that you ultimately decide to take suppresses your virus to undetectable levels, there shouldn't be any significant risk of developing drug resistance-- the very issue that raised cross resistance to drug classes in the pre-HAART era. Nevertheless, the issue of cross resistance within drug classes is a very important one and points out why we typically don't recommend therapy for those persons who are past their acute infection stage.

New drugs do come in a number of varieties-- newer members of exisiting classes, like second-generation PIs-- often with resistance profiles that permit their use after some degree of initial class-specific cross resistance (like the new PI, tipranavir) and new classes of medications, like fusion inibitors or integrase inhibitors (not yet).

Speaking to your specific proposed drug regimen, tenfovir/3TC/nevirapine should be a very well tolerated and potent drug regimen; though this combo has not actually been studied prospectively (yet). From extrapolation from the widely publicized Gilead 903 and 2NN clinical trials (you can look up this study on the Conference coverage section of TheBody), the combo should be very well tolerated and potent among persons with high viral loads (like acute infected persons). What has not been fully established is what types of medications most benefit the acute infected person- that is to say PI-based or NNRTI-based therapies, though I believe that the basic prinicple in this time is to prevent viral replication and destruction of CD4s-- so any drug regimen that can acheive the first goal will accomplish the second.

Good luck. BY



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