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

• Published in: The Journal of infectious diseases Vol. 192; no. 9; pp. 1597 - 1605
• Main Authors: Daar, Eric S. , Lynn, Henry S. , Donfield, Sharyne M. , Lail, Alice , O’Brien, Stephen J. , Huang, Wei , Winkler, Cheryl A.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.11.2005; University of Chicago Press; Oxford University Press
• Subjects: Adolescent; Adult; Alleles; Biological and medical sciences; Blood plasma; CD4 Lymphocyte Count; Chemokine CXCL12; Chemokines, CXC - genetics; Child; Cohort Studies; Disease Progression; Fundamental and applied biological sciences. Psychology; Genotype; Genotypes; Hemophilia A - complications; Hemophilia A - genetics; HIV 1; HIV Infections - complications; HIV Infections - diagnosis; HIV Infections - genetics; HIV Infections - immunology; HIV-1 - physiology; HIV/AIDS; Human immunodeficiency virus 1; Human viral diseases; Humans; Infections; Infectious diseases; Medical sciences; Microbiology; Miscellaneous; Receptors, CXCR4 - physiology; RNA; T lymphocytes; Tropisms; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral Load; Virology; Viruses; Disease development; Tropism; Immunopathology; Microbiology; HIV-1 virus; Retroviridae; Genotype; AIDS; Immune deficiency; Lentivirus; Virus; Infection; Viral disease; Human immunodeficiency virus; Stromal cell
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/496893

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.