Background.  Clinical studies have shown faster disease progression and stronger immune activation in human immunodeficiency virus (HIV)-1–infected females when compared with males for the same level of HIV-1 replication. Here we determine whether the elevated levels of HIV-1–induced interferon-alpha (IFN-α) production observed in females are associated with higher interferon-stimulated gene (ISG) expression levels in T cells, hence suggesting type-I IFN as a mechanism for the higher HIV-1–associated immune activation observed.

Methods.  T-cell and dendritic cell populations were isolated from treatment-naive chronically HIV-1–infected individuals enrolled in the Adult Clinical Trials Group 384 by fluorescence-activated cell sorting. The expression of 98 genes involved in Toll-like receptor and type I IFN signaling pathways were quantified using Nanostring technology.

Results.  Several ISGs were significantly correlated with HIV-1 viral load and/or CD4⁺ T-cell count. Higher expression levels of a subset of these ISGs were observed in cells derived from females as 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 is associated with higher ex vivo expression of several ISGs in females. This might contribute to higher levels of immune activation and the observed faster HIV-1 disease progression in females for a given level of viral replication.