CD4 intragenic SNPs associate with HIV-2 plasma viral load and CD4 count in a community-based study from guinea-bissau, West Africa

Branwen J. Hennig, Digna R. Velez-Edwards, Maarten F. Schim Van Der Loeff, Cyrille Bisseye, Todd L. Edwards, Alessandra Tacconelli, Giuseppe Novelli, Peter Aaby, Steve Kaye, William K. Scott, Assan Jaye, Hilton C. Whittle, Scott M. Williams, Adrian V. Hill, Giorgio Sirugo

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Abstract

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 languageEnglish (US)
Pages (from-to)1-8
Number of pages8
JournalJournal of Acquired Immune Deficiency Syndromes
Volume56
Issue number1
DOIs
StatePublished - Jan 1 2011

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ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Hennig, B. J., Velez-Edwards, D. R., Schim Van Der Loeff, M. F., Bisseye, C., Edwards, T. L., Tacconelli, A., Novelli, G., Aaby, P., Kaye, S., Scott, W. K., Jaye, A., Whittle, H. C., Williams, S. M., Hill, A. V., & Sirugo, G. (2011). CD4 intragenic SNPs associate with HIV-2 plasma viral load and CD4 count in a community-based study from guinea-bissau, West Africa. Journal of Acquired Immune Deficiency Syndromes, 56(1), 1-8. https://doi.org/10.1097/QAI.0b013e3181f638ed