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BACKGROUND: A substantial percentage (10%-15%) of HIV-infected individuals experience a sharp decline in CD4^sup +^ T-cell counts and progress to AIDS quickly after primary infection. Identification ofbiomarkers distinguishing rapid progressors (RPs) vs chronic progressors (CPs) is critical for early clinical intervention and could provide novel strategies to facilitate vaccine design and immune therapy.
METHODS: mRNA and microRNA (miRNA) expression profiles in the peripheral blood mononuclear cells (PBMCs) of RPs and CPs were investigated at 111 (22) days [mean (SD)] of HIV infection. The association of mRNA and miRNA expression with disease progression was examined by ROC analysis and Kaplan-Meier survival analysis.
RESULTS: Pathway enrichment analysis showed that genes with deregulated expression in RPs were primarily involved in apoptosis pathways. Furthermore, we found that 5 miRNAs (miR-31, -200c, -526a, -99a, and -503) in RPs were significantly decreased compared to those in CPs (P < 0.05). The decreased expression of these miRNAs was associated with a rapid disease of progression of HIV infection with a 94% predictive value as measured by the area under the curve. The upregulated predicted targets from the 5 signature miRNAs and all upregulated genes identified from mRNA microarray analysis converged to the apoptosis pathway. Moreover, overexpression of miR-31 in primary human T cells promoted their survival.
CONCLUSIONS: Our results have identified a distinct transcriptomic signature in PBMCs of RPs and pro vided novel insights to the pathogenesis of HIV infection.
© 2013 American Association for Clinical Chemistry
Multiple longitudinal studies have revealed dramatic variation in the outcome of untreated HIV-1 infection, ranging from rapid AIDS development in under a year to no progression decades later (1 ). The unique patho- genic development of HIV-infected patients with rapid progression, representing 10%-15% of the HIV- positive population (2 ), remains less understood than those with chronic progression or elite controllers. Limited studies previously carried out with this patient population have identified several viral, genetic, and immunologic factors that are associated with rapid dis- ease progression, such as the early emergence of CXCR4-utilizing HIV strains, risk single-nucleotide polymorphisms (SNPs)3 within interleukin-7Ra or Toll-like receptor loci, and high concentrations of IP-10 (interferon ? induced protein) in the plasma (3- 7). Several months after HIV seroconversion, plasma viremia reaches a steady state or viral set point,...