title: Early viral load and CD4+ T cell count, but not percentage of CCR5+ or CXCR4+ CD4+ T cells, are associated with R5-to-X4 HIV type 1 virus evolution.
abstract: HIV-1 infection is established by CCR5-utilizing (R5) variants, and CXCR4-utilizing (X4) variants emerge in approximately 50% of infected patients. We studied the role of CCR5 and CXCR4 expression before and 1 and 5 years after seroconversion in HIV-1 disease in a prospective study of 102 seroconverters. High percentages of CCR5(+) cells among total cells (relative hazard [RH], 2.55; 95% confidence interval [95% CI], 0.99-6.52), but not among CD45RO(-)CD4(+) and CD45RO(+)CD4(+) cells preseroconversion and among total cells and CD45RO(-)CD4(+) cells (RH, 2.70; 95% CI, 1.06-6.92 and RH, 3.54; 95% CI, 1.27-9.90, respectively) 5 years after seroconversion were associated with more rapid progression to AIDS. One year after seroconversion, high percentages of CXCR4(+) cells among total and CD45RO(-)CD4(+) cells were associated with delayed development of X4 variants (RH, 0.49; 95% CI, 0.20-1.21 and RH, 0.41; 95% CI, 0.17-1.02, respectively), whereas no association was observed for the percentage of CCR5(+) cells. In a larger study population, high early serum viral RNA and low CD4(+) T cell numbers were associated with more rapid development of X4 variants. Our results exclude target cell availability as a driving force for R5-to-X4 virus phenotype evolution.
authors.affiliation: Sanquin and the Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, 1066 CX Amsterdam, The Netherlands.
authors.forename: Ronald P
authors.initials: RP
authors.lastname: van Rij
authors.forename: Mette D
authors.initials: MD
authors.lastname: Hazenberg
authors.forename: Birgit H B
authors.initials: BH
authors.lastname: van Benthem
authors.forename: Sigrid A
authors.initials: SA
authors.lastname: Otto
authors.forename: Maria
authors.initials: M
authors.lastname: Prins
authors.forename: Frank
authors.initials: F
authors.lastname: Miedema
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D015331:Cohort Studies; D018450:Disease Progression; D019143:Evolution, Molecular; D005434:Flow Cytometry; D015726:Giant Cells / Q000502:physiology; D015658:HIV Infections / Q000503:physiopathology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D019562:Viral Load
chemical_list: D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4