Herpes simplex virus (HSV) suppressive therapy in HSV-2/HIV-1 co-infected women is associated with reduced markers of inflammation in the systemic but not the mucosal compartment

Herpes simplex virus 2 (HSV-2) infection has been associated with higher genital chemokine levels and increased numbers of human immunodeficiency virus type 1 (HIV-1) target cells in the genital mucosa, suggesting local immunologic alterations may increase HIV-1 replication.  Archived specimens from an 18 week randomized, placebo-controlled, cross-over trial of daily HSV-2 suppressive therapy (valacyclovir) in HIV-1 and HSV-2 dually infected women conducted in Peru were analysed to determine the effect of HSV-2 treatment on the systemic and mucosal inflammatory environment.  Levels of 31 cytokines in plasma and 14 cytokines in endocervical swabs were assessed by multiplex bead array at time points collected weekly throughout the trial. Valacyclovir treatment was found to significantly reduce plasma levels of CXCL10, but did not significantly alter concentrations of the other factors measured in either compartment, suggesting that new HSV-2 therapies must aim to reduce local inflammation of the mucosae to reduce viral transmission.