Phenotype and functionality of CD8+ T cells before and after cART are related to the viral reservoir size in people living with HIV-1
Date
2019
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Abstract
Background: the persistence of latently infected t-cells remains the major obstacle to cure HIV. special emphasis has been placed to identify the characteristics of cD8+ t-cells (cD8tcs) associated with viral control. We aimed to determine the relationship between the quality of the immune response before and after antiretroviral treatment (cart) and HIV persistence on cart.
Methods: 18 subjects were enrolled during acute/early HIV infection (median 2 month post-infection). blood samples were obtained at enrollment (baseline sample, pre-cart) and after 18 months post-art (on-cart). Phenotypic (cD45ro, ccr7, cD95, PD-1) and functional (cD107, cytokines) markers were studied on bulk and HIV-specific cD8tcs by flow cytometry, in both samples. cell- associated HIV DNa forms (total and integrated) were quantitated by real-time Pcr in samples on-cart. Data was analyzed using non-parametric statistics.
Results: spearman’s correlations showed that higher HIV-integrated DNa levels on samples on-cart were related to lower expression of baseline cD107+ cD8tcs and lower proportion of HIV-specific terminal effector (te) cD8tcs (p=0,003 and p=0,049). Moreover, total HIV DNa levels post-cart directly correlated with baseline HIV-specific PD-1+cD8tcs.
HIV-integrated DNa levels positively correlated with the percent- age of PD-1+cD8tcs (p< 0,0001), and inversely with the per- centage of bi- and trifunctional cD8tcs (p=0,024 and p=0,048) at on-cart samples. Moreover, direct correlations between the percentage of effector memory cD8tcs at: bulk, HIV-specific, and PD-1+ compartments and the levels of HIV-integrated DNa were observed (p= 0,005, p=0,0003 and p=0,004). similarly, HIV-integrated DNa inversely correlated with the proportion of cD8tc te in the same three compartments (p=0,016, p=0,0003 and p=0,007). Finally, negative correlations between HIV- integrated DNa levels and the percentage of naïve and stem cell memory cD8tcs (r=-0,561, p=0,002; r=-0,398, p=0,044) were found.
Conclusions: Different immune parameters evaluated pre- and post-cart were related to HIV persistence. overall, results suggest that an exhausted and dysfunctional HIV-specific immune response, both before and after treatment initiation, was related to a higher reservoir size at 18 months post-cart. this should be considered when designing functional cure approaches. also, the potential use of these parameters as markers of reservoir size and/or remission should be studied.
Description
Fil: Figueroa MI. Fundación Huésped, Buenos Aires; Argentina
Fil: Cahn P. Fundación Huésped, Buenos Aires; Argentina
Fil: Sued O. Fundación Huésped, Buenos Aires; Argentina
Fil: Cahn P. Fundación Huésped, Buenos Aires; Argentina
Fil: Sued O. Fundación Huésped, Buenos Aires; Argentina