HIV-1-infected individuals with HLA-B*57 alleles progress slowly to disease, in part due to restricted CD8+ T cell responses. However, some HLA-B*57 individuals progress faster to disease. We hypothesized that additional host correlates may explain the risk of disease progression. PBMC from six HLA-B*5701 patients were analyzed longitudinally and divided into high-risk and low-risk progressors based on CD4 counts at baseline. We developed a custom made Taqman array to measure mRNA expression of 34 anti-HIV-1 restriction factors. We named the overall gene expression as Cumulative Restriction or CuRe score. T cell activation, viral load, T cell counts and plasma sCD14 were also determined for all patients at all time-points. The CuRe score was significantly increased in high-risk progressors (p<0.0001), with particular increases of APOBEC3F, APOBEC3G, tetherin, SAMHD1 and interferon-inducible genes. CuRe score correlated with viral load only in low-risk progressors (R>0.60, P<0.001). T cell activation was significantly elevated in high-risk progressors (p<0.05), and correlated with a decline in CD4+ T cell counts (Spearman R=-0.92, P<0.0001). Plasma sCD14 was significantly elevated in high-risk progressors, and correlated with CuRe score (R=0.79, P<0.001). In our study, we show that combining a multiple gene expression array of anti-HIV-1 restriction factors and immunological parameters provide important measures of risk for disease progression in HLA-B*5701 individuals.
- Copyright © 2013 by The American Association of Immunologists, Inc.