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The participation of Dr. Renslow Sherer in this Forum is made possible in part by an unrestricted educational grant from Abbott Laboratories.

Ask the Experts about Drug Resistance and Staying Undetectable
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Intelence?
Mar 9, 2008

Dear Dr.

I am switing out the PI's for Intelence. Currently on boosted Lexiva with Truvada. Going to start just Truvada and intelence. I have tested resistance to the old nnrti's. My dr. wants to do VL within 1 mos to ensure it works. If not, the plan is to resume the old combo. Stopping PI cause of GI issues, and reduce pill and copay count. Plus High trigycerides from ritonavir. Sound reasonable?

Response from Dr. Sherer

Honestly, no. I can't give you a fully informed answer, because I lack too much information that is specific to your case, but your plan concerns me, so I will explain why and offer you and your physician some alternatives to consider.

In general, a single drug switch for toxicity is a well-accepted strategy, provided that the relative potency of the two agents is similar. It is also true that the demands on a single drug in this setting when the viral load is below detection are less than in the setting of initial therapy with high viral load.

Still, the maximal potency of etravirine (Intelence) is in the range of 1-1.5 log, and somewhat lower if you have one or more NNRTI mutations. If you have never been treated with an NNRTI, this might be true in your case, but more likely you have failed an NNRTI-based regimen in the past, which is the reason that your doctor has chosen etravirine.

If I were your physician, I would be reluctant to rely on etravirine as the anchor of your current regimen. The information in your past resistance tests will inform this question, but even then, minority species that might harbor other NNRTI mutations may not be detected by standard resistance testing. Another important key factor would be whether there is any evidence that tenofovir is compromised by either the K65R (I would guess not) or multiple TAMs from earlier NRTI therapies, including AZT or D4T.

You and your doctor have other options that you can consider. The GI toxicity of one PI such as boosted fAPV may be reduced by a substitution of another boosted PI such as atazanavir or the newer lopinavir tablet formulation, for example. To address the copay issue, Kaletra offers coformulation of ritonavir and lopinavir. Unless the triglyceride were severely elevated, e.g. over 6-800, I would be reluctant to factor this into this decision, as your continuing virologic control should be your highest priority. This option might also be useful to you, since one part of your plan is to return to the current regimen if it fails - so perhaps the search for a better tolerated PI is worthwhile.

Finally, even if your proceed with this plan, I might suggest that you and your doctor first add the etravirine to your current regimen and observe side effects and virologic control. If all is well, you could then observe the effect of discontinuing the PI.



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