Immunological Profile of Heterosexual Highly HIV‐Exposed Uninfected Individuals: Predominant Role of CD4 and CD8 T‐Cell Activation

Background. Altered T cell subset distribution patterns in uninfected individual highly exposed to human immunodeficiency virus (HIV) have been explained either as a consequence of viral exposure or as a surrogate marker of low susceptibility to infection. Methods. Multiple genetic and immunological parameters were studied prospectively in 21 HIV-serodiscordant heterosexual couples. Results. We found changes of both CD4 + and CD8 + T cells in highly HIV-exposed, uninfected individuals, with a lower level of naive and CD28 + T cells and higher levels of HLA-DR + T cells and CD4 + T cells expressing CCR5 and memory CD4 + T cells than in control subjects. The changes in memory and activated T cells observed in highly HIV-exposed, uninfected partners were directly correlated with plasma viral load (PVL) of the HIV-1-infected partners, whereas changes in naive and CD4 + CD28 + T cells observed in highly HIV-exposed uninfected partners were inversely correlated with PVL of the HIV-1-infected partners. We were only able to detect HIV-1-specific T-cell responses in a few highly HIV-exposed uninfected partners. Conclusions. These data suggest that the peripheral immune cells of highly exposed, uninfected individuals responded according to the level of HIV exposure from the partner, even though evidence of specific HIV stimulation is rarely seen.