754 
Transmission of Subtype C HIV-1 during Acute Infection in Mother-Infant Pairs in Zambia
F Hoffmann1, X He1, J West2, P Lemey3, T M'Soka4, C Kankasa4, C Mitchell5, and Charles Wood*1
1Univ of Nebraska, Lincoln, US; 2Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, US; 3Univ of Oxford, UK; 4Univ of Zambia Teaching Hosp, Lusaka; and 5Univ of Miami, Miller Sch of Med, FL, US
Background: Little is known
about HIV transmission during an acute infection, and even less is known about
transmission to infants during acute infection of the mother. Our goal is to
explore genetic variation associated with transmission of subtype C HIV-1 viruses
in mother-infant pairs where dual seroconversion has occurred, and to examine
longitudinal changes in viral populations, focusing on contrasting differences
between mother and infant.
Methods: Blood samples from 3
mother-infant pairs were obtained at several time points before and shortly
after seroconversion. Using maximum likelihood and Bayesian methods, the V1-V5
region of env was analyzed to
investigate relationships among mother and infant viral populations, track
changes in time in the viral populations, and characterize genetic variation
associated with transmission and disease progression. The rates of molecular
evolution, the selective regime, and the number of putative glycosylation sites
were also compared.
Results: We
identified 3 mother-infant pairs that dually seroconverted after delivery. All
viruses used CCR-5 as a co-receptor. Maternal and infant viral populations
showed similar patterns of genetic variation throughout the study. Genetic
diversity in env increased with time but
the initial mother and infant populations showed little genetic
differentiation. Estimates of variation between the initial mother and infant
populations’ samples overlapped with estimates of variation within them. In 2
cases, the median number of glycosylation sites was smaller in the infant
relative to the mother. Non-synonymous changes were not evenly distributed
along the fragment of the Env protein studied; instead they clustered at
concordant regions within each mother-infant
pair. Evidence for this
parallel variation was also seen in the analyses of selective pressure, as some
positions appeared to be under positive selection in both mother and infant.
Estimates of the rates of molecular evolution were generally higher in infants
than in the corresponding mother, perhaps highlighting the more immature infant
immune selection.
Conclusions: We found that the
majority of the maternal viral quasispecies in the acutely infected mothers
were passed directly on to their infants. Infants’ viruses displayed similar
independent evolution patterns when compared with their mothers’, but seemed to
have higher rates of evolution, suggesting that such rates may be determined by
differences in the immune response between infants and adults.
|