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Resistance to PI's
Dec 6, 2004

Diagnosed + in November 2002 with a virus resistant to PI's (though I don't know to what extent; I guess that I should ask).

I'm treatment-naive and will likely go on meds soon as my CD4 is around 280 and VL is about 5,000. My doctor said my first regimen would be combivir and sustiva.

Does resistance to PI's significantly impact my long-term prognosis? I just learned today that my resistance was to PI's, which are credited to extending so many lives since their development in the '90s. (I knew that I had some resistance previously but was unaware of to what class of drugs.)

Is it worse to be resistant to PI's than other classes of drugs? This news really scared me.

Thank you for your response. This site is an amazing resource!

Response from Dr. Sherer

I will answer your question in general, though it would be better to know the exact mutations and number of mutations that you have. And of course, I urge you to talk to your doctor about these concerns.

You will recall that the PIs generally require multiple mutations before resistance develops. An exception is nelfinavir, to which resistance develops with only a D30N or L90M mutation. And with boosting of PIs with ritonavir, the number of mutations needed increases, as with lopinavir/r (Kaletra), for which 6-8 mutations are needed before decreased susceptibility is seen.

So if you have one, or even two, common PI mutations, this may be of little or no consequence if you are first started on a boosted PI such as lopinavir/r when you first receive a PI. Indeed, I would suggest that you and your doctor plan for what that first PI regimen would contain now in order to address this question and ease your mind. In all likelihood, you can identify a PI-based regimen that is likely to have activity.

There is little comparative data on the natural history of people who acquire PI mutations at baseline compared to those who acquire NNRTIs or NRTIs, in part because PI mutations are less common. My own answer would be no, its not worse to have these mutations, and it may be better than either an NNRTI mutation (which would likely result in the loss of the entire class) or an NRTI mutation, as even one or two can significantly compromise some members of the class.


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