HIV耐药性毒株检测方法和应用 .pptVIP

* From our discussion you can appreciate why results of resistance testing will depend on the specimen. Namely, whether plasmaRNA is assayed revealing the virus selected of the moment, OR if PBMC DNA is evaluated that includes latently infected provirus that is minimally expressed as RNA. The PBMC DNA provides some “history” of past virus including drug resistant mutants that have since been outgrown by wildtype virus. * A graphic presentation of the key resistance mutations is also very helpful, for two reasons. One, I think it’s useful for clinicians to become familiar, at least to some degree, with the mutation charts and algorithms by which genotypic assay results are translated into clinically useful information. Second, a graphical mutation chart like this highlights certain patterns of resistance mutations, such as the fact that many, if not most, mutations to a drug will also result in some degree of resistance to other drugs in that class as well; for example, M41L contributes to resistance to AZT, d4T, and Abacavir. RT mutation M184V may temporarily and partially reverse the effects of the mutations of AZT mutations on AZT susceptibility. However, if 3 of the listed mutations are present, the additional presence of M184V is not likely to reverse phenotypic AZT resistance One study reports increased low-level phenotypic resistance to 3TC with E44D and/or V118I mutations, in the absence of a concurrent M184V mutation [Hertogs. Antimicrob Agents Chemother 2000;44:568]. Another [DArminio-Monforte. 8th CROI; 2001; Chicago. Abstract 447.] reported no association over the short term between E44D or V118I and viral load responses to a 3TC-containing combination regimen Over the last several years, correlations between genotype and phenotype have been well established for the mutations that arise with monotherapy [Miller. AIDS 2000;14:163]. This slide shows NRTI resistance mutations. The amino acid residues involved are highly diverse and offer a pot