Emergence and persistence of CXCR4-tropic HIV-1 in a population of men from the multicenter AIDS cohort study

James C. Shepherd, Lisa P. Jacobson, Wei Qiao, Beth D. Jamieson, John P. Phair, Paolo Piazza, Thomas C. Quinn, Joseph B. Margolick

Research output: Contribution to journalArticlepeer-review

Abstract

We examined the emergence of CXCR4 (i.e., X4) tropism in 67 male human immunodeficiency virus type 1 (HIV-1) seroconverters from the Multicenter AIDS Cohort Study (MACS) who were selected to reflect the full spectrum of rates of HIV-1 disease progression. A mean of 10 serial samples per donor were evaluated by a laboratory-validated, commercially available assay to determine phenotypic coreceptor use. A total of 52% of men had dual- or mixed-tropic HIV-1 detected at 1 or more of the time points tested. Use of X4 by HIV-1 was detected more frequently among men who developed AIDS (defined as a CD4+ T cell count of < 200 cells/μL and/or an AIDS-defining illness) ≤ 11 years after seroconversion than among those who did not (P = .005), as well as among men who exhibited a total T cell count decline (i.e., a CD3+ inflection point), compared with those who did not (P = .03). For men in whom both X4 virus and an inflection point were detected, emergence of X4 virus preceded the inflection point by a median of 0.83 years. The median CD4 + T cell count at first detection of X4 viruses before the onset of AIDS was 475 cells/μL. We conclude that HIV-1 variants that used X4 frequently emerged at high CD4+ T cell counts and may contribute to the decrease in T cell numbers during late HIV-1 infection.

Original languageEnglish (US)
Pages (from-to)1104-1112
Number of pages9
JournalJournal of Infectious Diseases
Volume198
Issue number8
DOIs
StatePublished - Oct 15 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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