title: HIV-1 phenotypic reverse transcriptase inhibitor drug resistance test interpretation is not dependent on the subtype of the virus backbone.
abstract: 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.
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa. michelle.bronze@gmail.com
authors.forename: Michelle
authors.initials: M
authors.lastname: Bronze
authors.forename: Kim
authors.initials: K
authors.lastname: Steegen
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.forename: Hans
authors.initials: H
authors.lastname: De Wolf
authors.forename: Maria A
authors.initials: MA
authors.lastname: Papathanasopoulos
authors.forename: Margriet
authors.initials: M
authors.lastname: Van Houtte
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Stevens
authors.forename: Tobias Rinke
authors.initials: TR
authors.lastname: de Wit
authors.forename: Lieven J
authors.initials: LJ
authors.lastname: Stuyver
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use; D024921:Drug Resistance, Multiple, Viral; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase