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Picking Your Brain!
Aug 4, 1999

Hi Dr. Mark, Thanks for the service you provide here. You're wonderful! Here's my quandry: My partner has had some really bad treatment experiences. In the midst of his 3+ years of treatment, he has developed a pretty extensive resistance to most drugs. A genotype was done one day after a drug holiday was ordered. The holiday lasted about 4 months. He swtiched to a new Dr. at the end of the holiday, who relys on phenotypes much more than genos. A pheno was ordered, with the idea that the geno was probably not the thing to do ( drugs for 4 months). The results of the pheno came back, and using these results, the doc ordered ddi+HU, ABC, and APV. These seemed to work well in vitro, I guess. My question is this: On the original geno, a major mutation was detected at codon 74 (L74V). 1) Shouldn't this indicate that ddi would NOT work? 2) Could the addition of HU help overcome this mutation? 3) Is there anything fishy about the time frame when the pheno was ordered? 4) If the ddi doesn't work, would it be feasible just to switch to d4t+HU or would BOTH of the NRTI's have to be changed? (He can't use NNRTI's at all). Thanks for all your hard work. You make a difference is SO many lives! (I'm really worried...hope to hear from you.) Michael

Response from Dr. Holodniy

It's hard to interpret without me seeing the results of both tests. And given that they were done at different times, they could have very different results. After a drug holiday, we would expect some, if not all, of the wild type virus to return. Therefore the ddI resistant virus might not be detectable phenotypically. The predominant mutant virus will still be lurking in the background. HU probably will not overcome the ddI resistance. It does contribute by it's action to generate super-normal levels of ddI inside cells. There is controversy over whether HU also helps other drugs like d4T. This data is not clear. MH

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