Female Genital Tract Shedding of CXCR4-Tropic HIV Type 1 Is Associated with a Majority Population of CXCR4-Tropic HIV Type 1 in Blood and Declining CD4+ Cell Counts

Abstract This study compared HIV-1 genotypes shed over time (≤3.5 years) in the vaginal secretions (VS) and blood plasma (BP) of 15 chronically infected women. Analysis of predicted coreceptor tropism (CCR5=R5, CXCR4=X4) for quasispecies shedding revealed three patterns: (1) viral quasispecies shed in both VS and BP were restricted to R5-tropism at all time points, (2) quasispecies shed in VS were restricted to R5-tropism at all time points but X4 quasispecies were identified in the BP at one or more time points, and (3) quasispecies shed in matched VS and BP both contained X4-tropic viruses. Overall, the frequency of X4 quasispecies circulation in VS was 2-fold less than in BP and detection of X4 virus in VS was more likely to occur when X4 quasispecies comprised more than 50% of BP viruses (p=0.01) and when declines in blood CD4+ lymphocyte levels were the greatest (p=0.038). Additionally, the mean number of predicted N-glycosylation sites between matched VS and BP samples was strongly correlated (r=0.8...