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Will the virus in general population mutate to be resistant to PI'...
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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?
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87972_tn?1322664839
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?

Bill
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Avatar_m_tn
Excellent question...we do know the SOC drugs dont cause mutations like the PI`s...if this is true,there is always a price and trade off in anything,
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Avatar_m_tn
Another example of why this monster is evil.
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My doctor alluded to this.  He said in future, HCV treatment will be more like HIV tx - taylored to ind. according to exposures.  He said inhibitors are not the panacea.
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Avatar_n_tn
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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