What Causes the limiting
Feb 13, 2001
I am facing the possibility of starting HAART in the near future. I am trying to understand all the various pros and cons about my options. Some of my concern about PIs is that there is a history of heart disease in my family, and I have always had borderline high blood pressure. For that reason, PIs don't look to be an attractive option. But on the other hand, I read if I fail a NNRTI based regime, I have lost the class in case of "one mutation" and that this is an effective class in salvage. So my question is, what cause the "one mutation?" Is is strictly a matter of adherence? Or is it something else. Thank you for taking the time to answer my question.
Response from Dr. Pavia
Good questions. For some classes of antivirals, the virus cannot become resistant without accumulating a number of mutations. For the non nukes, 3TC, and nelfinavir, a single mutation can do it. Mutations occur every day when the virus is replicating, and those mutations that have an advantage will survive and become the "fittest" (Kind of a viral game of survivor).
If the virus isn't replicating, then mutations will not occur. So, if a regimen is effective, then the key issue comes down to adherence. There are other reasons that a regimen may not work, like low drug levels, but this is not an issue for the non nukes. So, whatever regimen you take, it is like deciding to have a child. You are committed and you have to do it right!
It is reasonable to consider delaying using the current PI's if you have a strong family history of heart disease (especially disease before 50 in the men or before 60's in the women). The other risk factors need to be added in to the occasion: smoking, high blood pressure, blood cholesterol, exercise, and age. That having been said, we have not yet really proven that there is a cardiac risk, although it may be to soon to have seen it.
Options to consider in your setting would include a non nuke based regimen, or, if your viral load is not very high, an abacavir based regimen. There is pretty good evidence, although not conclusive, that if your viral load is over 100,000 then the abacavir based approach has a higher chance of failing.
Hope this helps.
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