HIV+-specific CD8+ T-cells antiviral activity correlates with cell phenotype and polyfunctionality in subjects who initiated treatment at different time points after acute infection

SALIDO, J; TRIFONE, C; GHERARDI, MM; CZERNIKIER, A; LAUFER, N; FIGUEROA, MI; SUED, O; GHIGLIONE, Y; RUIZ, MJ; CARUSO MP; SALOMON, H; TURK, G

Mar del Plata

Congreso; SAIC-SAI-SAFIS 2018; 2018

The success of strategies to achieve HIV functional cure will largely rely on the ability of HIV-specific CD8+ T-cells (CD8TC) to clear reactivated infected cells. AIM: To evaluate the phenotype and function of expanded HIV-specific CD8TCs, from subjects initiating combined antiretroviral therapy (cART) at different times post-infection.25 HIV+ subjects on 1-year cART, that either initiated treatment earlier (ET: Early treatment, 13 subjects) or later (DT: Delayed treatment, 12 subjects) after infection, were recruited. PBMCs were stimulated with peptides pools spanning Nef/p24 proteins during 14 days and then CD8TC phenotype (CD45RO, CCR7, CD95 and PD1 expression) and function (CD107a/b, IFN-, IL-2, MIP-1 and TNF-) were analyzed. Direct and indirect antiviral activity of expanded CD8TCs against autologous CD4TCs was evaluated by VITAL Assay (VA) and Viral Inhibition Assay (VIA), respectively. Non-parametric statistics were applied.Expanded cells were highly polyfunctional, regardless of cART initiation timing. Memory/effector phenotype distribution showed a preservation of memory stem-cell (CD8TCSCM, p≤0.005) and central memory (CD8TCCM, p≤0.01) subsets in ET. Contrary, DT showed a fully-differentiated profile (p≤0.005). PD-1 expression was clustered in HIV-specific terminal effector cells (CD8TCTE, p≤0.001). Also, PD-1 directly correlated with CD8TC functionality. Expanded CD8TCs from DTs and ETs were highly capable of mediating antiviral activity, and it correlated with the proportion of fully differentiated effector cells (VIA p=0.04, VA p=0.028) as well as with CD8TC polyfunctionality and PD-1 expression (VA p=0.0249 and p=0.016, respectively).In sum, despite HIV-specific CD8TC response is dampened in subjects under cART, it could be selectively stimulated and expanded in vitro, presenting a high proportion of cells able to carry-out multiple effector functions. cART initiation timing had an impact on the memory phenotype, most likely reflecting different times of antigen persistence. Overall, these results have important implications for designing strategies for modulating CD8TCs with the objective of reaching HIV functional cure.