title: HIV reverse-transcriptase drug resistance mutations during early infection reveal greater transmission diversity than in envelope sequences.
abstract: BACKGROUND
  Drug resistance mutations (DRMs) can serve as distinct, nonpolymorphic markers for evaluating diversity of expressed HIV-1. We screened for DRMs during early-acute viremia and examined the diversity in reverse transcriptase (RT) relative to envelope (env) in cases of transmitted drug resistance.
  
  
  METHODS
  We evaluated 111 longitudinal plasma samples collected every 2-7 days from 15 individuals who seroconverted for HIV-1 infection in 1994-2000. The samples were screened with sensitive polymerase chain reaction assays for the commonly transmitted M41L and K70R mutations and for K65R, which was undetected by bulk sequencing. Mutation-positive samples were further characterized by clonal sequencing of RT and env V1-V3.
  
  
  RESULTS
  Drug resistance mutations were detected in 4 of 15 seroconverters at 5-50 days of viral nucleic acid expression; most mutations disappeared about the time of seroconversion. Clonal sequencing verified low-level K65R at frequencies of 0.4%-4.9%. In each case, K65R coexisted unlinked with variants carrying 2-5 thymidine analog mutations at frequencies of 1.6%-23.0%. In one seroconverter, variants with M184V and nonnucleoside RT inhibitor mutations were also identified at first RNA expression. Each seroconverter displayed a homogeneous V1-V3 env population.
  
  
  CONCLUSIONS
  Reverse-transcriptase DRMs demonstrate that the breadth of variants in transmission may be greater than what is reflected in envelope sequences.
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Lipscomb
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: William M
authors.initials: WM
authors.lastname: Switzer
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Jin-fen
authors.initials: JF
authors.lastname: Li
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Silvina
authors.initials: S
authors.lastname: Masciotra
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: S Michele
authors.initials: SM
authors.lastname: Owen
authors.affiliation: Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Johnson
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D019295:Computational Biology; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000635:transmission / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D019562:Viral Load; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D054299:env Gene Products, Human Immunodeficiency Virus; D054303:HIV Reverse Transcriptase
keywords: HIV seroconversion; HIV transmission; HIV-1 diversity; acute HIV-1 infection; minority resistance mutations; multiplicity of infection