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HIV Drug ResistanceHIV Drug Resistance
          
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Why worry about low NRTI load?
Nov 22, 2002

I hope you can explain the logic of current treatment strategies to me. This situation is very close to my own situation right now. My experience has been that just adding or switching a single drug of the same class where some resistance has already occurred only provides limited surpression, even if one is fully compliant, for a limited period of time.

So here's my question. If someone has some resistance to all of the currently available NRTIs and NNRTIs but has not ever had resistance to PIs, and continues to have >30 T cells and <1000 VL on several successive tests for several months while on treatment, why not just continue with taking these drugs? I know that conventional treatment thinking is to avoid additional resistance and mutations. But if it may take a long time to develop more resistance while one waits for more options in other classes of drugs (e.g. PIs, entry inhibitors, integrase inhibitors). Isn't it better to gain some benefit from partially surpressive drugs regimens than to go "naked" off medication entirely and let the virus do more immune system damage? I realize that one might be "writing off" these classes of drugs for the future, but it seems to me that just as in the past any new NRTIs or NNRTIs will likely have some cross-resistance to existing NRTIs and NNRTIs and would only be of marginal treatment intensification or additive benefit anyway.

It seems to me if one can get another year or two of reasonably good virus surpression out of existing NRTIs and NNRTIs now, he may still be in a better place when switching to entirely new classes of anti-HIV medications (e.g. Kelatra + T-20) to obtain more complete and durable surpression. Thanks for explaining this.

Response from Dr. Little

You have asked a very good question - which may have a different answer for people taking different drugs or with a different viral load. As I understand your situation, you have resistance to the NRTIs and NNRTIs yet have fairly good control of your virus on a regimen of these drugs. You have not yet tried any of the PI drugs. So if this is correct, the concern with continuing this partially suppressive regimen depends completely on the regimen and the types of resistance mutations you already have. In general, we do try to switch to a completely suppressive regimen (if there is one that we believe will do the job) in people with viral relapse on their current regimen. The level of virus which will prompt providers to recommend a switch may also vary (generally greater than 1,000 to 10,000, depending on the care provider).

You are correct that there is good data to support the continued use of a nonsuppressive treatment regimen over no treatment at all, but this does not really relate to your question of whether it is better to switch now to a completely suppressive regimen or continue the one you are on and hope for a durable suppression and the availability of new drugs before a switch is really needed. The difficulty is in predicting how long you will continue to have relatively good control on your current regimen. In general, I become more conservative (i.e. change less readily) when the treatment choices become more and more restricted, but I cannot say I would generally continue an incompletely suppressive regimen if I really thought that by going to a PI based regimen you could achieve complete suppression. This would depend on the rate of your CD4 decline and the number and type of resistance mutations that you already have on your current regimen.

So - I cannot give you an easy answer - since I would really need to know when new drug classes were going to be available and I would need to be able to predict better than I can now whether the regimen you are currently taking will last that long. Sorry - but the question is very complicated and very individualized.


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