HIV-1 clade B pol evolution following primary infection

PLoS One. 2013 Jun 28;8(6):e68188. doi: 10.1371/journal.pone.0068188. Print 2013.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active / methods
  • CD4 Lymphocyte Count / methods
  • Cohort Studies
  • Evolution, Molecular
  • Female
  • Genes, Viral / genetics*
  • Genes, pol / genetics*
  • Genetic Variation / genetics
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV-1 / genetics*
  • HLA Antigens / genetics
  • Humans
  • Longitudinal Studies
  • Middle Aged
  • Viral Load / methods
  • Young Adult

Substances

  • HLA Antigens