Herpes simplex virus type 2 (HSV-2; herpes) exacerbates human immunodeficiency virus type 1 (HIV) by unclear mechanisms. These studies tested the impact of HSV-2 on systemic T-cells and HIV reservoirs.

Peripheral blood mononuclear cells from HIV-infected women on antiretroviral therapy who were HSV-2 seropositive or seronegative and HIV-uninfected controls were analyzed by flow cytometry. Cell-associated HIV DNA and RNA were quantified in the absence or presence of activating stimuli, recombinant interleukin 32γ (IL-32γ), and a RUNX1 inhibitor. RNA was assessed by nanostring.

CD4, but not CD8, T-cell phenotypes differed in HIV⁺/HSV-2⁺ versus HIV⁺/HSV-2⁻ (overall P = .002) with increased frequency of CCR5⁺, CXCR4⁺, PD-1⁺, and CD69⁺ and decreased frequency of CCR10⁺ and CCR6⁺ T-cells. The changes were associated with higher HIV DNA. Paradoxically, IL-32, a proinflammatory cytokine, was lower in subpopulations of CD4⁺ T-cells in HSV-2⁺ versus HSV-2⁻ women. Recombinant IL-32γ blocked HIV reactivation in CD4⁺ T-cells and was associated with an increase in RUNX1 expression; the blockade was overcome by a RUNX1 inhibitor.

Herpes is associated with phenotypic changes in CD4⁺ T-cells, including a decrease in IL-32, which may contribute to increased HIV reservoirs. Blocking IL-32 may facilitate HIV reactivation to improve shock and kill strategies.