Stromal cell-derived factor-1 genotype, coreceptor tropism, and HIV type 1 disease progression.
This study used a well characterized cohort of human immunodeficiency virus type 1 (HIV-1)-infected hemophiliacs to define the relationship between the SDF1-3'A allele, the plasma HIV-1 coreceptor tropism, and the natural history of HIV-1 disease. Subjects heterozygous or homozygous for the SDF1-3'A allele experienced higher rates of decline in CD4+ T cell counts over time than did those without the allele (P=.009). Moreover, they had an increased risk of progression to acquired immunodeficiency syndrome and death, a relationship that persisted even when baseline plasma HIV-1 RNA levels and CD4+ T cell counts or CCR5 Delta 32 and CCR2-64I genotype were controlled for. This relationship was even stronger in a subgroup of subjects for whom tropism data were available. Subjects with the SDF1-3'A allele were also more likely to have detectable X4-tropic viruses (P=.012), and, when tropism was included in the survival analyses, the effect of the SDF1-3'A allele on disease progression was no longer significant. Therefore, the increased frequency of X4-tropic viruses in subjects carrying the SDF1-3'A allele may explain the observed adverse effect that this allele has on the natural history of HIV-1 disease.
Daar
Eric S
ES
Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90502, and the David Geffen School of Medicine at UCLA, Los Angeles, USA. edaar@labiomed.org
Lynn
Henry S
HS
Donfield
Sharyne M
SM
Lail
Alice
A
O'Brien
Stephen J
SJ
Huang
Wei
W
Winkler
Cheryl A
CA
D000293:Adolescent; D000328:Adult; D000483:Alleles; D018791:CD4 Lymphocyte Count; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000175:diagnosis* / Q000235:genetics* / Q000276:immunology; D015497:HIV-1 / Q000502:physiology*; D006467:Hemophilia A / Q000150:complications / Q000235:genetics; D006801:Humans; D019718:Receptors, CXCR4 / Q000502:physiology*; D019562:Viral Load
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D019718:Receptors, CXCR4