title: Emergence and persistence of CXCR4-tropic HIV-1 in a population of men from the multicenter AIDS cohort study.
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/muL and/or an AIDS-defining illness) < or =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/microL. 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.
authors.affiliation: School of Medicine, Johns Hopkins University, MD, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Shepherd
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Wei
authors.initials: W
authors.lastname: Qiao
authors.forename: Beth D
authors.initials: BD
authors.lastname: Jamieson
authors.forename: John P
authors.initials: JP
authors.lastname: Phair
authors.forename: Paolo
authors.initials: P
authors.lastname: Piazza
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Quinn
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Margolick
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000453:epidemiology* / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D000328:Adult; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D018450:Disease Progression; D015483:HIV Antibodies / Q000097:blood*; D015658:HIV Infections / Q000453:epidemiology* / Q000276:immunology / Q000503:physiopathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D008297:Male; D015995:Prevalence; D019718:Receptors, CXCR4 / Q000378:metabolism
chemical_list: D015483:HIV Antibodies; D019718:Receptors, CXCR4
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