Associations of CCR5, CCR2, and stromal cell-derived factor 1 genotypes with human immunodeficiency virus disease progression in patients receiving nucleoside therapy.
Genotype data for CCR5, CCR2, and stromal cell-derived factor 1 (SDF-1) were obtained from 354 human immunodeficiency virus type 1 (HIV-1)-positive subjects who were being treated with nucleosides. Associations with HIV-1 load, HIV syncytium-inducing (SI) phenotype, CD4 cell count, and disease progression were analyzed. No differences in HIV-1 load or CD4 cell count were observed between wild type (+) and variant genotypes. Changes from non-SI to SI viral phenotype were more frequent in heterozygotes with a 32-bp deletion (Delta32) in the CCR5 gene than in + homozygotes (40% vs. 7%; P=.01). In a multivariate analysis, heterozygous CCR5 Delta32 was associated with reduced hazard of progression (hazard ratio, 0.32; P=.02). Subjects homozygous for the SDF-1 3'A variant had more-rapid disease progression (P=.008). The SDF-1 homozygous 3'A variant was related to more-rapid disease progression, and CCR5 Delta32 was associated with reduced rates of hazard for disease progression in nucleoside-treated subjects.
Lathey
J L
JL
Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA. jlathey@zycos.com
Tierney
C
C
Chang
S Y
SY
D'Aquila
R T
RT
Bettendorf
D M
DM
Alexander
H C
HC
Santini
C D
CD
Hughes
A M
AM
Barroga
C F
CF
Spector
S A
SA
Landes
J E
JE
Hammer
S M
SM
Katzenstein
D A
DA
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D018450:Disease Progression; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D005838:Genotype; D015726:Giant Cells / Q000821:virology; D015658:HIV Infections / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D009705:Nucleosides / Q000627:therapeutic use*; D012367:RNA, Viral / Q000032:analysis; D054390:Receptors, CCR2; D019713:Receptors, CCR5 / Q000235:genetics*; D019707:Receptors, Chemokine / Q000235:genetics*; D019562:Viral Load
D019380:Anti-HIV Agents; C515334:CCR2 protein, human; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D009705:Nucleosides; D012367:RNA, Viral; D054390:Receptors, CCR2; D019713:Receptors, CCR5; D019707:Receptors, Chemokine