title: Genetic diversity as a marker for timing infection in HIV-infected patients: evaluation of a 6-month window and comparison with BED.
abstract: BACKGROUND
  It has been reported that the increase in human immunodeficiency virus (HIV) sequence diversity in drug resistance surveillance specimens may be used to classify the duration of HIV infection as <1 or >1 year. We describe a mixed base classifier (MBC) optimized to categorize the duration of subtype B infections as <6 or >6 months on the basis of sequences for drug resistance surveillance specimens and compared MBC findings with those of serologic methods.
  
  
  METHODS
  The behavior of the MBC was examined across a range of thresholds for calling mixed bases. MBC performance was then evaluated using either complete pol sequences or sites reflecting evolutionary pressures (HLA selection sites, sites that increased in entropy over the course of infection, and codon positions).
  
  
  RESULTS
  The MBC performance was optimal when secondary peaks on the sequencing chromatogram accounted for at least 15% of the area of primary peaks. A cutoff of <0.45% mixed bases in the pol region best identified recent infections (sensitivity = 82.7%, specificity = 78.8%), with improvement achieved by analyzing only sites that increased in entropy.
  
  
  CONCLUSIONS
  In an extended data set of 1354 specimens classified by BED, the optimized MBC performed significantly better than a simple MBC (agreement, 68.98% vs 67.13%). If further validated, the MBC may prove beneficial for detecting recent infection and estimating the incidence of HIV infection.
authors: National HIV and Retrovirology Laboratories, Public Health Agency of Canada, Ottawa, Canada.
authors: Manon
authors: M
authors: Ragonnet-Cronin
authors: Stéphane
authors: S
authors: Aris-Brosou
authors: Isabelle
authors: I
authors: Joanisse
authors: Harriet
authors: H
authors: Merks
authors: Dominic
authors: D
authors: Vallée
authors: Kyna
authors: K
authors: Caminiti
authors: Michael
authors: M
authors: Rekart
authors: Mel
authors: M
authors: Krajden
authors: Darrel
authors: D
authors: Cook
authors: John
authors: J
authors: Kim
authors: Laurie
authors: L
authors: Malloch
authors: Paul
authors: P
authors: Sandstrom
authors: James
authors: J
authors: Brooks
mesh_terms: D019540:Area Under Curve; D001483:Base Sequence; D002170:Canada / Q000453:epidemiology; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000235:genetics; D014644:Genetic Variation; D015658:HIV Infections / Q000453:epidemiology / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008969:Molecular Sequence Data; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D012372:ROC Curve; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013997:Time Factors
chemical_list: D012367:RNA, Viral; D012321:DNA-Directed RNA Polymerases