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Could this be the start of resistence?
May 21, 2002

My partner just back from the doctor with bad news. CD4 down from over a 1000 to 300. 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 large drop in the 3 months since his last blood work with only those issues. Nadir was CD4 252 and VL 48,000. His doctor wants another blood draw in 2 weeks. 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. Little

I would agree that a drop from 1000 to 300 in CD4 cell count is very surprising in this time period - especially with a viral load of only 1202. I would suggest that you look also at the CD4% - frequently, when there are large changes in the absolute number that don't make as much sense as we would like, you can look at the CD4%. This number changes less in response to interval colds and other stresses and may in fact not be nearly as bad as the absoulte CD4 cell count sounds.

In response to your questions: 1. Could this be the start of drug resistance - yes, it could. In general, the drugs 3TC and sustiva are quite susceptible (relative to many of the other drugs) to missed doses over time and while it is impossible to tell whether missed doses or potency is the issue, yes, I would be a bit concerned. 2. Which drugs - 3TC and sustiva are most likely. Cross resistance is high for the NNRTI if resistance to sustiva has developed. If resistance to 3TC has developed, it will probably affect abacavir responses most significantly. 3. Either the phenotype or genotype could be done to evaluate resistance to one or the other drug. In general, you are looking for fairly simple information and the genotype is cheaper and may be the prefered test in this case by many providers.

It is also true however, that we do occasionally see higher level relapses in viral load that are never explained and as long as the viral load returns promptly to undetectable and no resistance is detected, all may be well. Good luck.

HCV & use of nonsteroidal antiinflamatory drugs
On-Off treatment-resistence?

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