HIV-1 Phenotypic Reverse Transcriptase Inhibitor Drug Resistance Test Interpretation Is Not Dependent on the Subtype of the Virus BackboneReportar como inadecuado




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To date, the majority of HIV-1 phenotypic resistance testing has been performed with subtype B virus backbones e.g. HXB2. However, the relevance of using this backbone to determine resistance in non-subtype B HIV-1 viruses still needs to be assessed. From 114 HIV-1 subtype C clinical samples 36 ARV-naïve, 78 ARV-exposed, pol amplicons were produced and analyzed for phenotypic resistance using both a subtype B- and C-backbone in which the pol fragment was deleted. Phenotypic resistance was assessed in resulting recombinant virus stocks RVS for a series of antiretroviral drugs ARV-s and expressed as fold change FC, yielding 1660 FC comparisons. These Antivirogram® derived FC values were categorized as having resistant or sensitive susceptibility based on biological cut-off values BCOs. The concordance between resistance calls obtained for the same clinical sample but derived from two different backbones i.e. B and C accounted for 86.1% 1429-1660 of the FC comparisons. However, when taking the assay variability into account, 95.8% 1590-1660 of the phenotypic data could be considered as being concordant with respect to their resistance call. No difference in the capacity to detect resistance associated with M184V, K103N and V106M mutations was noted between the two backbones. The following was concluded: i A high level of concordance was shown between the two backbone phenotypic resistance profiles; ii Assay variability is largely responsible for discordant results i.e. for FC values close to BCO; iii Confidence intervals should be given around the BCO-s, when assessing resistance in HIV-1 subtype C; iv No systematic resistance under- or overcalling of subtype C amplicons in the B-backbone was observed; v Virus backbone subtype sequence variability outside the pol region does not contribute to phenotypic FC values. In conclusion the HXB2 virus backbone remains an acceptable vector for phenotyping HIV-1 subtype C pol amplicons.



Autor: Michelle Bronze , Kim Steegen, Carole L. Wallis, Hans De Wolf, Maria A. Papathanasopoulos, Margriet Van Houtte, Wendy S. Stevens,

Fuente: http://plos.srce.hr/



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