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Resistance patterns
May 24, 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. Boyle

That's a lot of questions and I'll give you a short answer to each one. Four years out of a regimen is not bad, but the breakthrough may reflect the nonadherence over the years that you mention. First, I would repeat the viral load to verify that it is elevated and confirm adherence to the regimen, but >1000 is high for just a "blip", and, if confirmed, I would suspect resistance is likely. The most likely drugs affected would be 3TC and perhaps efavirenz. Resistance to 3TC with 184V has an adverse impact on didanosine and abacavir, but may increase sensitivity to zidovudine, stavudine and tenofovir. Resistance to efavirenz leads to cross-resistance to the entire NNRTI class. We generally do genotypes when doing a resistance test, but a phenotype is probably just as good in this case. Good luck.



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