Shorter survival of SDF1-3'A/3'A homozygotes linked to CD4+ T cell decrease in advanced human immunodeficiency virus type 1 infection.
The SDF-1 3'A allelic polymorphism has been reported to influence either positively or negatively the progression of human immunodeficiency virus type 1 (HIV-1) disease. Therefore, the SDF-1 genotype of 729 HIV-1-infected individuals pooled from 3 distinct cohorts was determined. A statistically nonsignificant association between the SDF1-3'A/3'A genotype and accelerated disease progression was evident among seroconverters (n=319), but a striking correlation of decreased survival after either diagnosis of AIDS according to the 1993 definition or loss of CD4(+) T cell counts <200 was observed. The relative hazards for SDF1-3'A/3'A homozygotes, compared with heterozygotes and wild-type homozygotes were 2.16 (P=.0047), for time from diagnosis according to the 1993 Centers for Disease Control and Prevention AIDS case definition (AIDS-'93) to death, and 3.43 (P=.0001), for time from CD4(+) T cells <200 to death. Because no difference in survival was observed after diagnosis according to AIDS-'87, the association of the SDF1-3'A/3'A genotype with the accelerated progression of late-stage HIV-1 disease appears to be explained for the most part by the loss of CD4(+) T lymphocytes.
Brambilla
A
A
AIDS Immunopathogenesis Unit, San Raffaele Scientific Institute, Milan, Italy.
Villa
C
C
Rizzardi
G
G
Veglia
F
F
Ghezzi
S
S
Lazzarin
A
A
Cusini
M
M
Muratori
S
S
Santagostino
E
E
Gringeri
A
A
Louie
L G
LG
Sheppard
H W
HW
Poli
G
G
Michael
N L
NL
Pantaleo
G
G
Vicenzi
E
E
D000163:Acquired Immunodeficiency Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D000328:Adult; D018791:CD4 Lymphocyte Count; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics* / Q000276:immunology; D015331:Cohort Studies; D003408:Cresols; D018450:Disease Progression; D004338:Drug Combinations; D005557:Formaldehyde; D005819:Genetic Markers; D005838:Genotype; D015497:HIV-1; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011379:Prognosis; D012118:Resorcinols; D015996:Survival Rate; D014766:Viremia / Q000209:etiology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D003408:Cresols; D004338:Drug Combinations; D005819:Genetic Markers; D012118:Resorcinols; D005557:Formaldehyde; C050719:phenoaldehyde