Will the virus in general population mutate to be resistant to PI's?
I was thinking about this recently. If somebody try's a PI, and fails / builds resistance to that PI, then re-infects somebody else in the general population with Hep C - won't the disease gain resistance to that PI? The new mutation could spread, and become the standard for Hep C (given the new resistance, will make it live longer). Are PI's a short term fix, that the virus will eventaully become resistant to?
That’s a very good question, and one that others are surely better qualified than I to answer. However, isn’t that why PI’s aren’t used as a monotherapy? My limited understanding is that PI’s are always used as an adjunct to standard IFN/riba treatment so the IFN will then cull escape variants produced via PI use. Whether this addresses *all* mutation production is interesting; perhaps ‘Willing’ or someone more familiar with this side of things will offer their thoughts. I hope they are sequencing results in trials to watch this as they proceed; it would be pointless as well as frightening to go forward with production if this were true, wouldn’t it?
It is well known from phase 1 trials of inhibitors including Telepravir that there is a mutation and rebound after 3-4 weeks.
The answer is combination threapy whereby the wild type is knocked out quickly with interferon supressing any variant until it litereally gives up and dies.
Ribavirin is crititcal to induce genetic sampling error to prevent a successful variant forming whilst the wild type is being knocked out.
The key to SVR is isto knock it out quick before it can regroup.
P.I resistant strains will be offset by lower infection rates and higher cure rates.
Remember Hepatitis C rates are reducing not increasing.
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