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OBJECTIVES: The human genetics of HIV-2 infection and disease progression is understudied. Therefore, we studied the effect of variation in 2 genes that encode products critical to HIV pathogenesis and disease progression: CD4 and CD209. DESIGN: This cross-sectional study consisted of 143 HIV-2, 30 HIV-1 + HIV-2 and 29 HIV-1-infected subjects and 194 uninfected controls recruited from rural Guinea-Bissau. METHODS: We genotyped 14 CD4 and 4 CD209 single nucleotide polymorphisms (SNPs) that were tested for association with HIV infection, HIV-2 plasma viral load (high vs. low), and CD4 T-cell count (high vs. low). RESULTS: The most significant association was between a CD4 haplotype rs11575097-rs10849523 and high viral load [odds ratio (OR): = 2.37, 95% confidence interval (CI): 1.35 to 4.19, P = 0.001, corrected for multiple testing], suggesting increased genetic susceptibility to HIV-2 disease progression for individuals carrying the high-risk haplotype. Significant associations were also observed at a CD4 SNP (rs2255301) with HIV-2 infection (OR: = 2.36, 95% CI: 1.19 to 4.65, P = 0.01) and any HIV infection (OR: = 2.50, 95% CI: 1.34 to 4.69, P = 0.004). CONCLUSIONS: Our results support a role of CD4 polymorphisms in HIV-2 infection, in agreement with recent data showing that CD4 gene variants increase risk to HIV-1 in Kenyan female sex workers. These findings indicate at least some commonality in HIV-1 and HIV-2 susceptibility.

Original publication

DOI

10.1097/QAI.0b013e3181f638ed

Type

Journal article

Journal

J Acquir Immune Defic Syndr

Publication Date

01/01/2011

Volume

56

Pages

1 - 8

Keywords

AIDS Serodiagnosis, Adult, CD4 Antigens, CD4 Lymphocyte Count, Cell Adhesion Molecules, Disease Progression, Female, Genotype, Guinea-Bissau, HIV Infections, HIV-1, HIV-2, Haplotypes, Humans, Lectins, C-Type, Linkage Disequilibrium, Logistic Models, Male, Middle Aged, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Receptors, Cell Surface, Viral Load