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Resistance patterns
May 8, 2002

Two weeks ago, I asked this question in the Resistance forum and have not received a reply. People at conferences or on vacation?

My partner just back from the doctor with bad news. CD4 down from over a 1000 to 800. Viral load from undectectable to 1202. With the exception of a couple of minor virals blips (< 1000), he has been undectectable since shortly after starting his first and only cocktail - Epivir, Zerit, Sustiva - in Dec. 1998. Now I know that having had a cold, lack of sleep, poor diet, recreational drugs (pot), stress, lack of sleep, etc. could all affect his T cell count and viral load, but I would not have expected such a drop in the 3 months since his last blood work with only those issues. Nadir was CD4 252 and VL 48,000. His doctor just completed a new blood draw and will run a genotype in addition to another CD4 and viral load. It will be 2 weeks before the results are back. In the meantime, he is stay on the 3TC, D4T, and efavirenz. He has tolerated this regimen very well with just a few minor annoying type side effects which resolved, for the most part, within a couple of weeks.

Questions: 1) He's not been 100 compliant - missing about 1 or 2 doses a month, as well as several hours late fairly frequently. Given the compliance record, nadir, and current numbers, would you suspect resistence? 2) If resistence is suspected, which drug(s) would be the most likely candidate(s)? 3) If resistence is confirmed, what are the cross-resistence patterns to other NRTIs and NNRTIs? 4) Which test(s) for resistence would you recommend in this instance?

Response from Dr. Aberg

The first thing I always do is to repeat the CD4 count and viral load to make sure it is real. You are correct that with an infection such as a cold that you may see a "blip" in the viral load and a slight decrease in the CD4 count. I also look at the percent CD4 to see if there really has been a change. It may not be such a big drop at all and more a reflection of the change of the absolute white blood count for reasons that you mention.

If in fact your partner has virologic failure as confirmed by the repeat viral load being detectable, then I agree that the genotype may be useful. So, let me try to answer your questions in order.

1. It sounds like overall that your partner has been pretty compliant with his meds, but even so, resistance may have developed especially if he missed doses consecutively.

2. The most likely candidates are 3TC (epivir) and efavirenz (sustiva).

3.For the most part, once you have resistance to one non-nucleoside reverse transcriptase inhibitor (NNRTIs), the whole class is gone. I would not switch one NNRTI for another. The nucleosides (NRTIs) are quite different and the associated mutations can be quite complex and probably much more than I can write on this forum. There is a really good web site which goes into great detail about resistance testing.

4. I would recommend a genotype at this time only. I rarely use a phenotype except when there are so many mutations and I am looking for some type of salvage even though it seems unlikely or I have some questions regarding the results of the genotype. I think your partner's genotype will be straightforward and he has several options for therapy.

resistance testing

EFV,d4t & ddL
Stop meds? Doctor laughs

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