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A question about mutations
Sep 7, 2004

Are there HIV mutations that are known to be harmless? Do we know which ones they are. Also when mutations naturally occur, can you naturally have one or two that are M184V or K103N or do those occur ONLY when you are on treatment. Which are the mutations then that naturally occur in your body? Do we know their names?

Response from Dr. Sherer

Yes, there are many mutations that have not been associated with any alteration in the virologic, immunologic, or clinical response to therapy, and thus that appear to be harmless. These are called 'polymorphisms'.

Two facts result in a high frequency of mutations in all possible locations of the HIV genome. First, HIV is a high volume infection, with 10 billion virons produced daily; and second, HIV replication is a sloppy, highly error-prone process, with mutations occurring every 10,000 cycles. If you do the math, you can see that thousands of mutations (or 'polymorphisms')are produced daily, and many pairs of mutations also occur.

So, yes, it is reasonable to expect that virus containing the M184V and the K103N are produced along with the many other polymorphism-containing viruses. Polymorphisms can be named in the same way we do the mutations that are associated with clinical resistance to medications.

A word of caution: I am reluctant to assert that all of these polymorphisms are 'harmless'. So far, we have not observed a negative impact on response to treatment in their presence, but there is still much that we don't know about drug resistance. We can only say that we haven't defined a negative role for polymorphisms at this time.

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