Stromal Cell–Derived Factor–1 Genotype, Coreceptor Tropism, and HIV Type 1 Disease Progression
Journal of Infectious Diseases
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.
Daar, Eric S.; Henry S. Lynn; Sharyne Donfield; Alice Lail; Stephen J. O'Brien; Wei Huang; and Cheryl Winkler. 2005. "Stromal Cell–Derived Factor–1 Genotype, Coreceptor Tropism, and HIV Type 1 Disease Progression." Journal of Infectious Diseases 192, (9): 1597-1605. http://nsuworks.nova.edu/cnso_bio_facarticles/579
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