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Follow up on Future Regimine
Mar 19, 2005

Dr. Young, To follow up on your last answer, how much better is the toxicity of today's drugs compared to 4-5 years ago? Furthermore, if you don't expect theraputic vaccines in the near future, how much better can the toxicity get in the next 5 years with existing medication? Can you see a day when there is a once a day pill with much much less toxicity to the organs?

Response from Dr. Young

Thanks for your post.

In general, the short- and long-term tolerability of medications has improved in recent years. (I won't bite on the 4-5 year point, since it's difficult to quantitate exactly when things have improved.) We've learned a lot (via evidenced-based medical studies) about which combinations of medications to use, and which ones not to use. Unexpected failures of seemingly rational combinations, like tenofovir/abacavir/3TC or tenofovir/ddI/efavirenz highlight the dangers in just assuming that combinations will work.

The example of the advances in NRTI or protease inhibitor classes illustrate this thesis: recent once-daily fixed dose combo NRTIs, tenofovir, or the PIs, atazanavir (Reyataz) and fosamprenavir (Lexiva, Telzir).

The case for improvements in the tolerability and toxicity of medications are clearly exemplified by the PIs-- improved tolerability, improved cholesterol toxicity. For the case of fosamprenavir, no dietary restriction.

How much better will things get in the next 5 years? It's pretty difficult to predict-- rather than trying to anticipate yet-to-be developed drugs, it's probably more accurate (and less speculative) to say that we will continue to refine our understanding of how to better combine and dose medications will continue. We'll also see continued and improving long-term surveillance for toxicities.

We already have once-daily combination therapies; there is a tenofovir/FTC/efavirenz combination pill in development. Will the toxicity of the combinations be better? The combo pills will only be as "non-toxic" as their components, so we'll need to continue to support such research to be sure.

Remember that this is a prediction of how things may develop. Medications have clearly improved since the early days of combination therapy, but are not non-toxic to 100% of persons who take them. Fortunately, for those who do develop side effects or toxicity, we have a sufficient number of alternatives that effective therapy can be found for many. Lastly, while fear of or aversion to side effects are entirely understandable, these aversions should not be taken as a reason not to use or provide access to potentially life-saving medications.

I hope this answers your questions. BY



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