title: Selective vertical transmission of HIV-1 antiretroviral resistance mutations.
abstract: OBJECTIVE
  To examine the patterns of vertical transmission of zidovudine (ZDV) resistance mutations.
  
  
  METHODS
  HIV-1 reverse transcriptase codons 10-250 were sequenced from 24 pairs of ZDV-exposed women and their HIV-infected infants as part of the Women and Infants Transmission Study.
  
  
  METHODS
  Viral RNA was extracted from tissue culture supernatants and sequenced using fluorescent dye-primer chemistry and an automated sequencer.
  
  
  RESULTS
  For 17 of these pairs, maternal and infant sequences were identical to one another and lacking known ZDV resistance mutations. The remaining seven maternal sequences contained known mutations associated with ZDV resistance at reverse transcriptase codons 70, 210, 215 and 219. In each case where the maternal HIV isolate showed a pure mutant species, the infant sequence was identical. When the maternal sequence showed the presence of a sequence mixture at codon 70 or 219, the infant's virus showed only wild-type sequence even when the ZDV-resistant mutant was quantitatively dominant in the mother. The single maternal HIV isolate showing mixed sequence at codon positions 210 and 215 transmitted an unmixed mutant to the infant at both positions. When maternal mixtures were present at sites not associated with ZDV resistance, only the dominant species appeared in the infant.
  
  
  CONCLUSIONS
  When maternal HIV isolates contained mixed wild-type and ZDV-resistant subpopulations, only a single component of the mixture could be detected in the infected infants. Resistance mutants without the codon 215 mutation were not transmitted from mixtures, even when the mutants formed the majority of circulating maternal virus. In perinatal HIV transmission, specific ZDV-resistant HIV genotypes circulating in the maternal virus pool may influence whether infection in the infant will be established by a wild-type or ZDV-resistant HIV strain.
authors.affiliation: Division of Infectious Diseases, Beth Israel Deaconess Medical Center, Harvard School of Medicine, Boston, Massachusetts 02215, USA.
authors.forename: R C
authors.initials: RC
authors.lastname: Colgrove
authors.forename: J
authors.initials: J
authors.lastname: Pitt
authors.forename: P H
authors.initials: PH
authors.lastname: Chung
authors.forename: S L
authors.initials: SL
authors.lastname: Welles
authors.forename: A J
authors.initials: AJ
authors.lastname: Japour
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D001483:Base Sequence; D004279:DNA, Viral; D004352:Drug Resistance, Microbial / Q000235:genetics; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000276:immunology / Q000635:transmission / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008969:Molecular Sequence Data; D009154:Mutation; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D015215:Zidovudine / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D054303:HIV Reverse Transcriptase