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Follow-up To "Resistant Mutations"
Jun 30, 2011

Dr. McGowan,

I just read this question to you. In your answer, you mentioned that mutations/resistance may not always show up on the genotype and possible to not become aware of them until after you start treatment. I've been reading about just this. I think some refer to them as archived resistance.

My genotype showed I was resistant to NNRTI's like Atripla, due to the K103N mutation. I still haven't started meds as my CD4 has been around 750 and low vl. After reading about these archived resistances that may not show up initially, I wondered whether I could run into this problem. I know, no one can say and why worry about something until you have to, right? I'm just curious how often this happens--where you're told you have many options only to find out that was wrong? Do you rarely see it in your patients? Do you have many patients treatment naive who are just about resistant to every med?

One last question--- Everyone is either infected with a strain that is resistant or not at all, right? You don't develop more resistances from not being on meds yet? I know you can from being on meds and not adherent.

Thanks!

Response from Dr. McGowan

Thanks for your thoughtful questions.

It is not common to run into problems with archived mutations in a person who has never received treatment. The strain has to make up less than 20% of the overall population of virus to be missed.

Broad resistance to all or most meds in someone who was never treated is extremely rare (there was one reported case a few years ago).

It is true that the virus will not pick up drug resistance mutations if a person is not taking any meds to put pressure on it. The one exception is the Co-receptor antagonist (maraviroc/Selzentry). This drug blocks how the virus attaches to the CD4 cell. The virus can use one of 2 pathways (attaching to CCR5 or CXCR4 on the CD4 cell surface). Most virus choose CCR5. Over time there can be a shift away from CCR5 using to CXCR4 using virus that can occur even without exposure to the antagonist. So tropism (identifying which co-receptor the person's virus is using) should be measured just before maraviroc would be used to see the state of the virus at that moment.

Best,

Joe



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