TITLE

Stromal Cell--Derived Factor--1 Genotype, Coreceptor Tropism, and HIV Type 1 Disease Progression

AUTHOR(S)
Daar, Eric S.; Lynn, Henry S.; Donfield, Sharyne M.; Lail, Alice; O'Brien, Stephen J.; Wei Huang; Winkler, Cheryl A.
PUB. DATE
November 2005
SOURCE
Journal of Infectious Diseases;11/1/2005, Vol. 192 Issue 9, p1597
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
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 CCR5Δ32 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.
ACCESSION #
18544029

 

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