Peter: In reviewing the Chicago abstracts on indinavir and nelfinavir I wanted to review several issues that have been talked about before on this thread. These issues include BID dosing of protease inhibitors, viral resistance to initial PI with rechallenge with a second PI, dual PI therapy, and unique side effect profiles that would favor one PI over another.
In looking over the abstracts I've gleaned several conclusions regarding these issues:
1. BID dosing has proven effective for both IND and NELF.
2. Initial failure to NELF can be salvaged with an RTV/SAQ combo.
3. Another paper showed that cross resistance between IND and RTV were high (90% range), but that viral strains resistant to IND, RTV, and SAQ were still sensitive to NELF about 40% of the time.
4. The PIs have unique metabolic effects on lipid and glucose metabolism. Several papers talked about Crixbelly. This is an increase in the visceral to abdominal fat ratio. People on Crix have noted increased abdominal girth that is being attributed to this drug. As yet I have not heard reports of this happening with nelfinavir. In fairness to crixivan and the others, this could be a characteristic shared with all the PIs, but as yet we do not know for sure.For now, this is a negative tied to Crixivan so there may be a perceived advantage, real or imaginary to nelfinavir. Dan Musher, in a recent NEJM article, also described hyperglycemia high enough to require a change in treatment regimens in a number of patients on PIs. His paper suggested that this adverse effect may be a class effect that all of them share to some extent. Whether the Crixbelly phenomenon will be a class effect or not is, I believe, still up in the air. I would appreciate any thoughts that others may have on this issue.
Best regards,
Tim Kross |
