title: Discrepancies of HIV-1 reverse transcriptase resistance interpretation of insertions and deletions between two genotypic algorithms.
abstract: BACKGROUND
  Bioinformatics algorithms have been developed for the interpretation of resistance from sequence submission, which supports clinical decision making. This study evaluated divergences of the interpretation of the genotyping in two commonly used algorithms, using sequences with indels of reverse transcriptase genes.
  
  
  METHODS
  Sequences were obtained from virus RNA of patients failing highly active antiretroviral therapy from 2004 to 2011. Alignments were obtained using Clustal W including subtype B consensus and HXB2. Sequences with evidence of indels were submitted to the Stanford Resistance Database and to the Geno2Pheno to locate indel positioning and determine the resistance profile.
  
  
  RESULTS
  A total of 1,959 partial reverse transcriptase sequences were assessed, mostly subtype B (74%). Insertions and deletions were observed in 0.9 and 0.6% of sequences, respectively. Discordant insert positioning was assigned for most (90%) insertion sequences, with 27% discordances for deletions. Susceptibility differed for some antiretroviral drugs, predominantly for TDF, d4T and ETV, when sequences with deletions were evaluated.
  
  
  CONCLUSIONS
  Both indel positioning and its impact on drug susceptibility varies depending on the algorithm, a fact that might influence the clinical decision. Critical analysis of indel sequences with manual alignments is important, and its use alongside different algorithms may be important to better understand the outcomes of genotypic resistance prediction.
authors.affiliation: Laboratório de Retrovírus, Centro de Virologia, Instituto Adolfo Lutz, São Paulo, Brazil.
authors.forename: Giselle Ibette Silva
authors.initials: GI
authors.lastname: López-Lopes
authors.forename: André Minhoto
authors.initials: AM
authors.lastname: Lança
authors.forename: João Leandro
authors.initials: JL
authors.lastname: de Paula Ferreira
authors.forename: Luciana Oliveira
authors.initials: LO
authors.lastname: Souza
authors.forename: Luís Fernando
authors.initials: LF
authors.lastname: de Macedo Brígido
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D002648:Child; D019295:Computational Biology / Q000379:methods*; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D054643:INDEL Mutation; D008297:Male; D008826:Microbial Sensitivity Tests / Q000379:methods; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase