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Treatment interruption-mutation of virus?
Jun 3, 2001

If you have been on various treatments and you stop lets say 1-2 years (being able to resist), does the virus mutate to wild strains again? - if so, would that mean that you lose some of the resistances to past treatments? Thank you

Response from Dr. Cohen

No, thank You.

This is such an important question that there are at least two if not three large trials going on to explore exactly this issue.

What is clear so far - when someone is on a combination and HIV has started to regrow due to resistance, and then treatment is stopped, the viruses that are resistant to at least some of the medications that were used might fade away. And wild type, sensitive viruses will grow back. Why is this? Well, one key issue is that HIV appears to pay a price for creating drug resistance - and while these viruses can grow and can do harm when they do grow, they are not as "fit" as the wild type virus that is sensitive to the medication. And so, when there are no meds around, the wild type grows back, and often grows more than the drug resistant strains we see while on the meds. Now, the price that HIV pays to create resistance varies alot. So that some mutations appear to be "fully fit" - meaning that even off meds, these mutations are easily measured. Some however do fade as they are less fit.

But if they fade off meds, are they gone? The short answer is no. They often appear to be there, lurking around integrated in some of the memory cells of the immune system... ready to return in the mix if the drugs to which they are resistant are back in the picture.

So - the key question - Is it possible that having fewer resistant strains around will help when starting a new combo? That is the focus of the research. It may be that switching from combo A to B is more successful if we allow the virus that was resistant to combo A to fade away, and then start combo B. Especially if the virus' resistance to the meds used in combo A led to some cross resistance to the meds in combo B. Then, the logic goes, having fewer of these resistant viruses around could help in increasing the success rate when starting a new combo.

But the key is that we don't know yet. There are hints to suggest this might work - and this has led to these two large studies comparing just switching from combo A to combo B, versus stopping A for a few months, and then starting on B. Some time next year, if people help us by entering these studies, we'll know the answer to this question. Instead of just guessing.

But thanks for asking...

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