Presence of CXCR4-using HIV-1 in patients with recently diagnosed infection: correlates and evidence for transmission

J Infect Dis. 2012 Jan 15;205(2):174-84. doi: 10.1093/infdis/jir714. Epub 2011 Dec 5.

Abstract

Background: The prevalence and correlates of CXCR4-use in recently diagnosed patients and the impact of X4/DM transmission remain largely unknown.

Method: Genotypic coreceptor use determination on the baseline sample of 539 recently diagnosed individuals. Correlation of coreceptor use with clinical, viral and epidemiological data and with information on transmission events as obtained through phylogenetic analysis of protease and reverse transcriptase sequences. Results. CXCR4-use was predicted in 12 to 19% of the patients, depending on the interpretative cutoff used. CXCR4-use was correlated with lower CD4(+) T cell counts and subtype 01_AE infection. No association with viral load was observed. Seven (11%) of 63 transmission clusters and 4 (31%) of 13 donor-source pairs resulted from X4/DM transmission.

Conclusion: The results confirmed the relation between CXCR4-use at diagnosis and low baseline CD4+ T cell counts. Significantly more CXCR4-use was predicted in 01_AE infections, which may impose constraints on the use of CCR5 antagonists in certain regions of the world. Observations from the transmission cluster analysis contradict the hypothesis that R5 viruses are selected at transmission, and support the idea that R5 or X4/DM infections result from a stochastic process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4 Lymphocyte Count
  • Cluster Analysis
  • Evolution, Molecular
  • Female
  • Genotype
  • HIV Envelope Protein gp120 / genetics
  • HIV Infections / epidemiology
  • HIV Infections / immunology
  • HIV Infections / transmission*
  • HIV-1 / genetics*
  • HIV-1 / physiology*
  • Humans
  • Male
  • Peptide Fragments / genetics
  • RNA, Viral / analysis*
  • Receptors, CCR5 / genetics
  • Receptors, CCR5 / physiology*
  • Receptors, CXCR4 / physiology*
  • Sequence Analysis, RNA
  • Statistics, Nonparametric
  • Viral Tropism / genetics*

Substances

  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • RNA, Viral
  • Receptors, CCR5
  • Receptors, CXCR4