protease inhibitors should they be avoided?
Sep 14, 2002
Dr. Young, My question deals with reading over an article from poz magazine this month that questions the effectiveness of protease inhibitors? In the article it becomes clear that protease inhibitors can be the result of many vast side effects and also once resistance occurs to protease inhibitors, many options are not left? My question is, do you agree? Or do you believe that companies that produce protease inhibitors are right now working on new formulations to address this problem. Thanks,
Response from Dr. Young
Fred- thanks for your question.
I've not had a chance to read the POZ article, but yes, many drug, including protease inhibitors are associated with a number of side effects, and that resistance is a major limitation of treatment.
However, I think that this is a worse case scenario that might overly scare people away from therapies that are well tolerated and even life saving. Indeed, in my practice, we have several hundred patients who are tolerating protease inhibitor therapy very well, indeed, a recent survey of many of these persons offered them the opportunity to switch to other treatments (non-nuke-based) and nearly all refused to switch. I'd view this observation as a statement for the tolerability of PI-based treatments.
As for all treatments, it is important to recognize that there is a potential for side effects, some serious, some irreversible. Not everyone who receives such therapies experiences all such side effects, and as I have suggested above, many persons experience little or no side effects at all. A minority of persons experience severe, treatment-terminating side effects, particularly if properly monitored and counselled (recall that, paradoxically, that side effects are often worse with poor adherence).
As for resistance, there is a now outdated view that failure of the first protease inhibitor regimen meant that all subsequent PI treatments would fail. We now have substantial genetic, virologic and importantly, clinical data that demonstrates that this is not the case. Indeed, there is substantial evidence that cross resistance to all available non-nukes almost certainly happens after the failure of the first non-nuke. Furthermore, cross resistance among nucleoside drugs occurs, and is likely more common than previously thought.
In sum, the approach to therapy needs to appropriately take into account for issues related to the risks, benefits and tolerabilty of therapies. Improvements in these is the objective of all drug discovery programs. Newer protease inhibitors in development offer the potential for lower side effect and toxicity profiles, but the proof of this is waiting for the analysis of ongoing studies.
I hope that you find this useful. -BY
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