Faster HIV-1 disease progression among Brazilian individuals recently infected with CXCR4-utilizing strains

PLoS One. 2012;7(1):e30292. doi: 10.1371/journal.pone.0030292. Epub 2012 Jan 26.

Abstract

Introduction: Primary HIV infection is usually caused by R5 viruses, and there is an association between the emergence of CCXR4-utilizing strains and faster disease progression. We characterized HIV-1 from a cohort of recently infected individuals in Brazil, predicted the virus's co-receptor use based on the env genotype and attempted to correlate virus profiles with disease progression.

Methods: A total of 72 recently infected HIV patients were recruited based on the Serologic Testing Algorithm for Recent HIV Seroconversion and were followed every three to four months for up to 78 weeks. The HIV-1 V3 region was characterized by sequencing nine to twelve weeks after enrollment. Disease progression was characterized by CD4+ T-cell count decline to levels consistently below 350 cells/µL.

Results: Twelve out of 72 individuals (17%) were predicted to harbor CXCR4-utilizing strains; a baseline CD4<350 was more frequent among these individuals (p = 0.03). Fifty-seven individuals that were predicted to have CCR5-utilizing viruses and 10 individuals having CXCR4-utilizing strains presented with baseline CD4>350; after 78 weeks, 33 individuals with CCR5 strains and one individual with CXCR4 strains had CD4>350 (p = 0.001). There was no association between CD4 decline and demographic characteristics or HIV-1 subtype.

Conclusions: Our findings confirm the presence of strains with higher in vitro pathogenicity during early HIV infection, suggesting that even among recently infected individuals, rapid progression may be a consequence of the early emergence of CXCR4-utilizing strains. Characterizing the HIV-1 V3 region by sequencing may be useful in predicting disease progression and guiding treatment initiation decisions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amino Acid Sequence
  • Binding Sites
  • Brazil
  • Cohort Studies
  • Disease Progression
  • Female
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / metabolism
  • HIV Infections / diagnosis
  • HIV Infections / genetics
  • HIV Infections / immunology
  • HIV Infections / virology*
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / metabolism
  • HIV-1 / physiology*
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Receptors, CXCR4 / immunology
  • Receptors, CXCR4 / metabolism*
  • Receptors, Virus / metabolism
  • Sequence Homology, Amino Acid
  • Time Factors
  • Virus Internalization*
  • Young Adult

Substances

  • CXCR4 protein, human
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • Receptors, CXCR4
  • Receptors, Virus