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Interpreting Geno-Pheno Test Results
Jul 8, 1999

Dear Dr. Holodniy,

Thank you for all your good work on the forum!!

I am HIV+ treatment naive and I received the results of my Genotype and Phenotype tests. The Phenotype shows sensitivity to all meds except Zerit which is 10 fold intermediat/resistant. But the Genotype test shows resistance at Codon 214F. My Dr gave me a chart of the gene mutations by drug type. Codon 214 is listed as being a Secondary Multinucleoside Resistance. What does Multinucleoside Resistance mean? My Dr. and I are talking about initial treatment with Sustiva, AZT and 3TC. Would the 214F resistance change the effectiveness of any of these meds? Also, are AZT and 3TC still the best combo with Sustiva to achieve a protease sparing HAART regime. Is there anything else you would add for initial treatment?

Thanks for your help.

Response from Dr. Holodniy

Great questions! Sounds like you are on top of it. Multinucleoside resistance refers to certain mutations in the reverse transcriptase gene that confer broad class resistance to all or most of the drugs like AZT, 3TC, d4T, ddI, ddC, and Abacavir. Classic examples of these would be a Q151M, or a 69SS (two amino acid insertion after codon 69). A mutation at 214 is of unclear clinical significance. Some people believe it may be pre-AZT mutation, ie it develops fisrt before the classic mutation at codon 215. I am not sure what to make of the phenotypic resistance to d4T, when the genotypic change at codon 75 was not found. In addition, even in people who have had long term d4T experience, it is hard to demonstrate resistance to the drug. I think the regimen you propose is reasonable given the resistance results. It is the one regimen that has been compared to a protease inhibitor containing regimen (indinavir/AZT/3TC vs. sustiva/AZT/3TC) and found to be of equal potency. You did not say what your initial viral load was. If it is <100,000, you should have not trouble getting to undetectable levels (<50). If your viral load is >200,000, you may need to consider another agent in addition to what you are contemplating to get to <50.

MH



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