The role of a stromal cell-derived factor-1 chemokine gene variant in the clinical course of HIV-1 infection.
BACKGROUND
A G-to-A transition in the 3' untranslated region (UTR) of stromal cell-derived factor (SDF)-1 gene (SDF1-3'A) has recently been described, which in the homozygous state was associated with delayed disease progression.


OBJECTIVE
To analyse the effect of the SDF-1 polymorphism on AIDS-free survival and survival after AIDS diagnosis, also in relation to viral phenotype.


METHODS
Retrospective longitudinal study among 344 homosexual HIV-1-infected men.


RESULTS
A more rapid progression to AIDS (Centers for Disease Control and Prevention 1993 definition) was observed in SDF1-3'A/3'A subjects than in wild-type (SDF1-wt/wt) subjects (relative hazard, 1.75; P = 0.07). Using death as an endpoint, accelerated progression was no longer observed (relative hazard, 0.93; P = 0.84), suggesting a late protective effect of the SDF1-3'A/3'A genotype. Indeed, survival after AIDS diagnosis was significantly delayed in SDF1-3'A/3'A subjects (relative hazard, 0.40; P = 0.02). No effect of the SDF1-3'A/wt genotype on disease progression was observed. Interestingly, a higher frequency of Kaposi's sarcoma was observed as the AIDS-defining event among SDF1-3'A/3'A (40.0%) and SDF1-3'A/wt (30.6%) subjects than in SDF1-wt/wt subjects (17.0%). At the end of the study the total frequency of syncytium-inducing (SI) HIV-1 variants was lower in SDF1-3'A/3'A subjects (22.2%) than in SDF1-3'A/wt (32.5%) and SDF1-wt/wt subjects (40.5%), although not significantly. SDF-1 genotype did not influence the rate of evolution to SI HIV-1. Progression to AIDS after the emergence of SI HIV-1 was accelerated in SDF1-3'A/3'A subjects compared with the SDF1-wt/wt genotypic group (relative hazard, 4.04; P = 0.06).


CONCLUSIONS
In our study group, homozygosity for a G-to-A transition in the 3' UTR of SDF-1 is associated with an accelerated progression to AIDS but a subsequent prolonged survival after AIDS diagnosis.
van Rij
R P
RP
Department of Clinical Viro-Immunology, Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, and University of Amsterdam, Academic Medical Centre.
Broersen
S
S
Goudsmit
J
J
Coutinho
R A
RA
Schuitemaker
H
H
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology / Q000821:virology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D018450:Disease Progression; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D015497:HIV-1 / Q000235:genetics; D018451:Homosexuality, Male; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010641:Phenotype; D011446:Prospective Studies; D012189:Retrospective Studies; D017154:Stromal Cells; D017741:Survivors
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC