Emergence and persistence of CXCR4-tropic HIV-1 in a population of men from the multicenter AIDS cohort study.
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.
Shepherd
James C
JC
School of Medicine, Johns Hopkins University, MD, USA.
Jacobson
Lisa P
LP
Qiao
Wei
W
Jamieson
Beth D
BD
Phair
John P
JP
Piazza
Paolo
P
Quinn
Thomas C
TC
Margolick
Joseph B
JB
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
D015483:HIV Antibodies; D019718:Receptors, CXCR4
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