HIV-1 Clade B pol Evolution following Primary Infection

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Abstract

Objective:Characterize intra-individual HIV-1 subtype B pol evolution in antiretroviral naive individuals.Design:Longitudinal cohort study of individuals enrolled during primary infection.Methods:Eligible individuals were antiretroviral naïve participants enrolled in the cohort from December 1997-December 2005 and having at least two blood samples available with the first one collected within a year of their estimated date of infection. Population-based pol sequences were generated from collected blood samples and analyzed for genetic divergence over time in respect to dual infection status, HLA, CD4 count and viral load.Results:93 participants were observed for a median of 1.8 years (Mean = 2.2 years, SD = 1.9 years). All participants classified as mono-infected had less than 0.7% divergence between any two of their pol sequences using the Tamura-Nei model (TN93), while individuals with dual infection had up to 7.0% divergence. The global substitution rates (substitutions/nucleotide/year) for mono and dually infected individuals were significantly different (p<0.001); however, substitution rates were not associated with HLA haplotype, CD4 or viral load.Conclusions:Even after a maximum of almost 9 years of follow-up, all mono-infected participants had less than 1% divergence between baseline and longitudinal sequences, while participants with dual infection had 10 times greater divergence. These data support the use of HIV-1 pol sequence data to evaluate transmission events, networks and HIV-1 dual infection.

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Hightower, G. K., May, S. J., Pérez-Santiago, J., Pacold, M. E., Wagner, G. A., Little, S. J., … Pond, S. L. K. (2013). HIV-1 Clade B pol Evolution following Primary Infection. PLoS ONE, 8(6). https://doi.org/10.1371/journal.pone.0068188

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