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PI vs. NNRTI as First Therapy
Nov 27, 2000

I was recently diagnosed and following my first blood test, my doc recommended I start combination therapy (pending results of a second test next month). My T Cell count was 250 with a viral load of 50,000. My doc suggests either one of the following: 2NRTIs + 1 PI or 2NRTIs + 1 NNRTI (most likely Sustiva). Based on my numbers, would you tend to lean toward one or the other option? Thanks.

Response from Dr. Pavia

Based on your numbers, both would be very likely to work, based of course on your ability to adhere to the regimen (easy for us to say, hard for you to do).

I can summarize the pluses and minuses as I see them for you, but the bottom line is 1) what is right for you is the right choice, and 2) both are good choices. You would even be likely to do well on a three nucleoside regimen (such as AZT/3TC/abacavir.

A PI based regimen has some advantages (at this point we would use nelfinavir [viracept] or indinavir[crixivan] with low dose ritonavir to make it twice a day: We have the greatest experience and success building a second regimen on these regimens, there is a lot of long term experience with excellent immune responses, and we know the PI's are active in lymph node tissue and other compartments. It generally requires several mutations for the virus to become resistant. Disadvantages include the higher rate of problems with triglycerides, and to a lesser degree cholesterol, a small risk of diabetes, and at least a sense that body shape changes are more common on PI's.

NNRTI's have a number of pluses as well. Both nevirapine and efavirenz can be taken once a day, they are highly effective, there are very few pills to take relative to the PI's, there may be less effects on triglycerides, blood sugar, and probably cholesterol (the real answer here is complex). Body shape changes can occur on NNRTI regimens but seem to be less common. The disadvantage is the easy route to resistance (one mutation), the fact that once you have lost one NNRTI you have lost the class, and the perverse disadvantage that NNRTI's are excellent drugs to use in salvage.

It boils down to personal choice and tailoring it to you. Another choice that has become popular is to start with a PI based regimen, and then after a few months, consider switching to an NNRTI based or triple nuke regimen, especially if there seems to be a problem with lipids or body shape.

It is nice to have choices. Don't agonize too much, since all of the options you are considering are good ones.

Good luck

ATP

Andrew T. Pavia, M.D.



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