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Can better adherence lead to MORE resistance?
Jun 21, 2003

Hello Doctors!

I was scanning the highlights from the "12th International HIV Drug Resistance Workshop" and ran across this article:

http://www.hivandhepatitis.com/2003icr/12thdrug/documents/7_abstract.htm

I'll cut to the chase with the quote that puzzled me greatly:

"Conclusions: While improved adherence by treatment-experienced patients was associated with better virologic response, it may have promoted selection of more resistant HIV. Thus, interventions to improve adherence in such patients may be effective at preventing virologic failure but may have little or a negative impact upon acquisition of new antiretroviral resistance."

Now, there are plenty of qualifications in that quote, but even so: Can you explain how better adherence can lead to better virologic response while at the same time leading to more resistance?

Could this have something to do with diminished replication capacity in the resistant virus?

What does this mean (if anything) for patients trying very hard to achieve 100 adherence?

Thanks for your time and insight!

Response from Dr. Wohl

The situations in which the risk of developing HIV drug resistance is the LEAST is at the extremes of adherence. Meaning, if people are absolutely adherent OR are hardly taking their meds at all, the risk of resistance is the lowest.

It is in the middle that things get hairy. If you are 30% adherent and then get religion and become 60% adherent you may not have done yourself a great favor as far as preventing mutant drug resistant virus from popping up. This is because to get drug resistance you need a level of the drug in your blood that is high enough to force the virus to mutate to survive but not high enough to kill the virus. At 30% (I am making up the % adherence as no one knows what levels exactly correspond to risk of resistance) maybe there was too little drug around to prompt resistance mutations. But at 60%, viola! Mutants abound. Again - the % adherence I am using are examples. As you get real close to 100% adherence viral replication shuts down and resistance can't occur.

Take your medications 95-100% of the time and risk of resistance will be low and chance of optimally suppressing your virus, high.

DW



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