Baseline HIV type 1 coreceptor tropism predicts disease progression.
BACKGROUND
Human immunodeficiency virus type 1 (HIV-1) coreceptor tropism, the ability of the virus to enter cells via CCR5 or CXCR4, is a viral characteristic mediated by the envelope gene. The impact of coreceptor tropism on the natural history of HIV-1 infection has not been fully explored.


METHODS
Coreceptor tropism was measured using a recombinant virus single-cycle assay on plasma specimens obtained at baseline from 126 children and adolescents in the Hemophilia Growth and Development Study cohort who were enrolled from 1989 through 1990 and underwent follow-up through 1997.


RESULTS
Detectable CXCR4-using virus at baseline was associated with a lower baseline CD4(+) T cell count and a higher plasma HIV-1 RNA level. In addition, it independently predicted a greater decrease in CD4(+) T cell count over time (P<.001) and was associated with a 3.8-fold increased risk of progression to clinical AIDS.


CONCLUSIONS
This study demonstrates that coreceptor tropism, as assessed by this single-cycle assay, independently influences the natural history of HIV-1 disease.
Daar
Eric S
ES
Los Angeles Biomedical Research Institute at Harbor-University of California-Los Angeles (UCLA) Medical Center and the David Geffen School of Medicine at UCLA, Torrance, USA. EDaar@LABioMed.org
Kesler
Karen L
KL
Petropoulos
Christos J
CJ
Huang
Wei
W
Bates
Michael
M
Lail
Alice E
AE
Coakley
Eoin P
EP
Gomperts
Edward D
ED
Donfield
Sharyne M
SM
D000293:Adolescent; D000328:Adult; D018791:CD4 Lymphocyte Count; D002648:Child; D018450:Disease Progression; D015658:HIV Infections / Q000503:physiopathology*; D015497:HIV-1 / Q000472:pathogenicity*; D006467:Hemophilia A / Q000821:virology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008297:Male; D012367:RNA, Viral / Q000097:blood; D019713:Receptors, CCR5 / Q000276:immunology*; D019718:Receptors, CXCR4 / Q000276:immunology*; D014481:United States; D019562:Viral Load
D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4