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Trizivir patterns
Mar 4, 2004

Thanks for joining up here. After being diagnosed last May with CD4 800/VL85K, retested in October CD4 389/VL700K+. Treatment naive, started meds in October - Trizivir alone. It seems like it's worked well so far -- CD4 back over 400 and VL <400 right off the bat six weeks later. My questions are, first, how many hours should I keep my doses within? Once or twice it's been two or three hours off the 12-hour interval. And second, if resistance does develop, is it typically to Epivir in this combo and will Viread or Videx be able to be substituted to stay with a triple-NRTI, class-sparing combo? Whew! Got it all out.

Response from Dr. Sherer

I'll take your questions in order, but ask that you please read the whole response.

While its best for you to take the trizivir every 12 hours, I would not be overly concerned with delays of 1-2 hours. Remember that these drugs work at the intracellular level, so the plasma half-life does not tell us the important story, i.e. how long they last in an active form inside the cell. I can't give you a simple answer regarding how long is too long - recall that there are three difference compounds in this one pill, and they behave differently. What you want is for all three to alwys be acting together.

The evolution of resistance to TZV is well-characterized. As you suggest, it usually starts with resistance to 3TC in the first 6 weeks to 2-4 months, and then AZT mutations - called TAMS - start appearing. You do not want to wait long enough for all of this to happen before switching to another regimen in the event of virologic failure.

The other question is important - NO, so far all of the other 3 NRTI regimens have done poorly, and even very poorly, including DDI + 3TC + Tenofovir, and ABC + 3tC + tenofovir. These regimens have done so badly that they should never be used in a drug-naive person.

And finally, I have to inform you that I am not comfortable with this regimen for you at this time, given your baseline viral load, which you said was 700,000+. (If that were a typo, and your real viral load was 70,000, I would feel differently).

In the two trials in which a trizivir regimen were compared with either indinavir or nelfinavir, trizivir did worse in patients with a baseline viral load over 100,000. For that reason, until November 2003 the HHS Guidelines recommended that trizivir be used as an alternative regimen ONLY in patients with a baseline viral load below 100,000.

More recently, several trials have shown trizivir to be inferior to a regimen containing efavirenz and two NRTIs, and the current HHS guidelines recommend that trizivir be used only if an NNRTI or PI based regimen cannot or should not be used.

While your prompt CD4 and VL response is encouraging, it does not change my opinion, since the data from clinical trials suggests that you would do better on an NNRTI or PI-based regimen.

At a minimum, I urge you talk to your doctor about the points I have raised.

epivir and drug resistance tests unreliable for naive docs

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