In Human Immunodeficiency Virus primary infection, early combined antiretroviral therapy reduced γδ T‐cell activation but failed to restore their polyfunctionality

Summary Primary and chronic human immunodeficiency virus ( HIV ) infection alters γδ T‐cell features. However, there is no evidence about early combined antiretroviral therapy ( cART ) and γδ T‐cell dynamics. In the present study, HIV ‐positive individuals were divided into those with early primary infection ( EPI ) and those with late primary infection ( LPI ). The analysis of γδ T cells was performed by flow cytometry before and after therapy. Polyfunctional profile was assessed after in vitro peripheral blood mononuclear cell ( PBMC ) exposure to specific antigens. The results show that primary infection induced an expansion of V δ 1 T cells in LPI . Before treatment, a massive activation of γδ T‐cell subsets was observed in both groups of patients, that correlated with disease progression and was significantly reduced after cART introduction. Despite this, CD 107A‐expressing V δ 1 T cells in both groups were significantly fewer than in healthy donors, but were restored by therapy introduction. Polyfunctional analysis of V δ 1 T cells from HIV ‐positive individuals revealed a lower frequency of CD 107A +   CCL ‐4 + V δ 1 T‐cell subsets than healthy donors that persists after therapy. Functional profile of V δ 2 was similar to that in healthy donors before therapy but, at 6 months, a lower frequency of CD 107A, interferon‐ γ ‐ or tumor necrosis factor‐ α ‐producing V δ 2 T cells was observed in the EPI group. Finally, individuals with LPI showed a lower frequency of quadruple‐functional V δ 2 T‐cell subset. In conclusion, during primary HIV infection, the baseline V δ 1 T‐cell activation is correlated with immune reconstitution potential. Moreover, an altered γδ polyfunctional profile occurred, persisting after cART . Further studies are needed to understand whether a longer treatment of primary infection may increase γδ T‐cell functionality.