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G333D multidrug-resistance associated mutation?
Nov 29, 1999

Several reports have shown that mutations in codon 333 of the RT gene is associated to AZT plus 3TC resistance. However, the same works also showed that viral variants lacking that mutation were resistant to AZT plus 3TC. In addition, the presence of mutation M184V reverted the effect of AZT-resistance associated-mutations (I mean, at codon 67, 70, 41, 210, 215 and/or 219). So, the question is: what is the correct interpretation of a Genotype in which the changes M184V and AZT-resistance associated-mutations are present, but no changes are seen on codon 333?, I mean, it may be consider as an AZT+3TC resistant variant, or not?. Why?

Response from Dr. Holodniy

Great question!! Remember that most all of the genotypic resistance reports are from population based sequencing assays. HIV exists as a group of strains within the plasma. Population sequencing can only determine if a mutation is present among the strains (qualitatively). The assay can not tell you whether a 184 and 215 mutation exist within the same viral sequence(co-aggragate) or appear on two different strains. The studies confirming the interrelationship of these mutations are done using site directed mutagenesis, which can construct a virus with any single or multiple mutations at any position. So the labs are obligated to report what is there, and assume that strains exist with each mutation and therefore recorded as resistant to each. MH


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