864 Selective Vertical Transmission of Mixed Maternal HIV Variants R. Colgrove*1, G. Bauer2, J. Pitt3, S. Welles4 1Harvard Med Sch, Boston, MA; 2Univ of Minnesota, Minneapolis; 3Columbia Univ, New York, NY; and 4Boston Univ, MA
Background: We previously showed selective vertical transmission from mixed maternal HIV sequences at ZDV resistance codons. Here we extend those findings by examining all RT and protease codons in a larger maternal/infant cohort.
Methods: Nucleotide sequences for protease codon 1 through RT codon 324 were determined for HIV isolates from 18 mothers at or near delivery and compared with corresponding sequences for their infected infants at birth (5) or at first available positive culture (13) and with follow-up infant isolates within the first year (18). Bioinformatics software was created to analyze positions with mixed sequence in maternal and/or infant isolates.
Results: Fifty-four (54) total isolates from 18 mother/baby dyads were sequenced and aligned, yielding 68,526 readable nucleotide basecalls. We observed 327 mixed positions, including 208 maternal mixed sites, 3 infant birth mixtures, and 50 mixed positions at first available non-birth culture. Maternal mixtures per isolate (median 13.5, mean 14.3) were much more prevalent than mixtures in earliest infant isolates (median 0, mean 3.1) (p < 0.001, chi squared). Of 208 maternal mixed positions, only 17 were transmitted to the infant, all of these in 3 dyads with high numbers of maternal mixed positions (19, 20, and 26). Of the remaining 191 maternal mixtures, infants showed WT alone significantly more frequently (143/191, 75%), than mutant alone (48/191, 25%) (p < 0.05, chi squared). For resistance positions, maternal mixes were seen at RT codon 70 in 3 isolates, protease codon 63 in 2, and protease codon 82 in 1. WT alone was observed in the infant isolate in each (6/6) of these cases (maternal and infant isolate sequences were concordant for all unmixed resistance codon sites). Most mixtures were seen at usually silent 3rd codon position sites (69%) compared with 1st (20%) or 2nd positions (11%).
Conclusions: Only a small fraction of maternal HIV mixtures were transmitted to the infant and these were concentrated in a few dyads with high total numbers of mixtures. The WT component of maternal mixtures was more likely to be transmitted than the mutant component, including at a small number of resistance positions. Translationally silent mixtures were observed more often than non-silent variants. These results are consistent with a significant population bottleneck at vertical transmission with a bias toward WT genotypes.
