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Session 133 Poster Abstracts
Risk Factors for MTCT
Session Day and Time: Tuesday, 1 - 4 pm
Poster Hall


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.