Higher expression of several interferon-stimulated genes in HIV-1-infected females after adjusting for the level of viral replication (P3039)

Abstract

Background. Clinical studies have shown faster disease progression and stronger immune activation in HIV-1-infected females as compared to males for the same level of HIV-1 replication. This study assesses whether the elevated levels of HIV-1-induced IFN-α production observed in females were associated with higher interferon-stimulated gene expression levels in T cells, and hence suggesting type-I-IFN as a mechanism for the higher HIV-1-associated immune activation observed. Methods. Fluorescence activated cell sorting was used to isolate T cells and dendritic cells from PBMCs of treatment-naïve chronically HIV-1-infected individuals enrolled in ACTG 384. The expression of 98 genes involved in toll-like receptor and type-I-IFN signaling pathways were quantified using Nanostring technology on sorted cell populations. Results. Several interferon-stimulated genes were significantly correlated with HIV-1 viral load and/or CD4+ T cell count. Higher expression levels of a subset of these interferon-stimulated genes were observed in cells derived from females compared to males after adjusting for viral load, and were correlated to higher levels of T cell activation. Conclusion. These data show that higher IFN-α production and resulting higher ex vivo expression of several interferon-stimulated genes in females can contribute to higher levels of immune activation, and subsequently the observed faster HIV-1 disease progression in females for a given level of viral replication.