Introduction: EVG/c/FTC/TDF (Stribild) is non-inferior to PI/r-based regimens in cART switching patients. However, the effects of EVG/c/ FTC/TDF on immune system and HIV reservoirs have not been fully investigated. We investigated the impact of 24 weeks EVG/c/FTC/TDF on T-cell compartment and HIV reservoirs in HIV-infected patients, switching from a suppressive PI-based regimen. Methods: Thirty HIVpatients on effective PI-based regimens (HIV RNAB40 copies/mL) were followed for 24 weeks after switching to EVG/c/FTC/TDF. At baseline (W0), after 12 (W12) and 24 (W24) weeks we analyzed: HLA-DR/CD38/Ki67/CCR7/CD45RA/CD127/PD1 on CD4/CD8, IFNg/IL2 production after HIV/SEB exposure (flow cytometry), total HIV DNA (THIV-DNA), low levels HIV residua viremia (LL-RV) (qPCR). Statistical analyses: Friedman, Wilcoxon signed rank and Spearman correlation tests. Results: Patients were predominantly male (70%); median agewas 44; median HIV infection duration was 8 years; median time of HIV RNA suppression and cART duration was 5 and 6 years, respectively. At baseline, all patients were receiving TDFFTC (for a median of 5 years) in association with either DVR/r (47%) or ATV/r (53%). No HCV/HBV co-infections were found. Upon EVG/c/FTC/TDF introduction no changes in CD4 (634 cells/mm 3 vs. 614 cells/mm 3 vs. 582 cells/mm 3 ;p0.465) and in LL-RV (0 copies/mL vs. 0 copies/mL vs. 0 copies/mL; p0.081) were shown. Table 1 lists viro-immunologic results. Following EVG/c/FTC/TDF switch, we observed a significant reduction in HLA-DRCD38CD4(p0.016) and HLA-DR CD38CD8(p0.048). Interestingly, SEB exposure resulted in a significant reduction of IFN-g/IL-2-producing CD4(p0.024) and CD8(p0.003), IFNg-producing CD8(p0.024) and IL-2-producing CD4(p0.0001). No major differences were found after HIV stimulation. We failed to find any differences in T-cell exhaustion, proliferation and maturation, with the exception of a decrease in central memory CD4(p0.030). Similarly, no changes in THIV-DNA were found. At T0, LL-RV positively correlates with THIVDNA (r0.60, p0.005) and HLA-DRCD38CD4(r0.45, p0.022). Besides, THIV-DNA positively correlates with IFNgIL2 CD4and inversely with IFNgCD8(r0.51, p0.019; r0.45, p0.039, respectively) after SEB challenge. Interestingly, at W24 only the positive correlation between LL-RV and THIV-DNA (r0.58, p0.030) persists. Conclusions: In HIVvirologically suppressed patients, 24 weeks of EVG/c/FTC/TDF resulted in substantial reduction of activated T-lymphocytes andex-vivoT-lymphocyte susceptibility to exogenous super-stimulation. Despite failing to detect changes in HIV reservoirs following EVG/c/FTC/TDF, we capture an association between HIV DNA and both residual viremia and IFNg/IL2-producing T cells, suggesting poly-functional T-cell recruitment as a response to ongoingviral challenge. Altogether, these data would propose a favourable effect of EVG/c/FTC/TDF to preserve immune-activationdriven damage to T-cell homeostasis, in turn possibly containing cellassociated HIV viral burden in already virologically suppressed patients.

Switching to elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen (Stribild†): effects on T-cell compartment and HIV reservoirs

CASABIANCA, ANNA;ORLANDI, CHIARA;MAGNANI, MAURO;
2016-01-01

Abstract

Introduction: EVG/c/FTC/TDF (Stribild) is non-inferior to PI/r-based regimens in cART switching patients. However, the effects of EVG/c/ FTC/TDF on immune system and HIV reservoirs have not been fully investigated. We investigated the impact of 24 weeks EVG/c/FTC/TDF on T-cell compartment and HIV reservoirs in HIV-infected patients, switching from a suppressive PI-based regimen. Methods: Thirty HIVpatients on effective PI-based regimens (HIV RNAB40 copies/mL) were followed for 24 weeks after switching to EVG/c/FTC/TDF. At baseline (W0), after 12 (W12) and 24 (W24) weeks we analyzed: HLA-DR/CD38/Ki67/CCR7/CD45RA/CD127/PD1 on CD4/CD8, IFNg/IL2 production after HIV/SEB exposure (flow cytometry), total HIV DNA (THIV-DNA), low levels HIV residua viremia (LL-RV) (qPCR). Statistical analyses: Friedman, Wilcoxon signed rank and Spearman correlation tests. Results: Patients were predominantly male (70%); median agewas 44; median HIV infection duration was 8 years; median time of HIV RNA suppression and cART duration was 5 and 6 years, respectively. At baseline, all patients were receiving TDFFTC (for a median of 5 years) in association with either DVR/r (47%) or ATV/r (53%). No HCV/HBV co-infections were found. Upon EVG/c/FTC/TDF introduction no changes in CD4 (634 cells/mm 3 vs. 614 cells/mm 3 vs. 582 cells/mm 3 ;p0.465) and in LL-RV (0 copies/mL vs. 0 copies/mL vs. 0 copies/mL; p0.081) were shown. Table 1 lists viro-immunologic results. Following EVG/c/FTC/TDF switch, we observed a significant reduction in HLA-DRCD38CD4(p0.016) and HLA-DR CD38CD8(p0.048). Interestingly, SEB exposure resulted in a significant reduction of IFN-g/IL-2-producing CD4(p0.024) and CD8(p0.003), IFNg-producing CD8(p0.024) and IL-2-producing CD4(p0.0001). No major differences were found after HIV stimulation. We failed to find any differences in T-cell exhaustion, proliferation and maturation, with the exception of a decrease in central memory CD4(p0.030). Similarly, no changes in THIV-DNA were found. At T0, LL-RV positively correlates with THIVDNA (r0.60, p0.005) and HLA-DRCD38CD4(r0.45, p0.022). Besides, THIV-DNA positively correlates with IFNgIL2 CD4and inversely with IFNgCD8(r0.51, p0.019; r0.45, p0.039, respectively) after SEB challenge. Interestingly, at W24 only the positive correlation between LL-RV and THIV-DNA (r0.58, p0.030) persists. Conclusions: In HIVvirologically suppressed patients, 24 weeks of EVG/c/FTC/TDF resulted in substantial reduction of activated T-lymphocytes andex-vivoT-lymphocyte susceptibility to exogenous super-stimulation. Despite failing to detect changes in HIV reservoirs following EVG/c/FTC/TDF, we capture an association between HIV DNA and both residual viremia and IFNg/IL2-producing T cells, suggesting poly-functional T-cell recruitment as a response to ongoingviral challenge. Altogether, these data would propose a favourable effect of EVG/c/FTC/TDF to preserve immune-activationdriven damage to T-cell homeostasis, in turn possibly containing cellassociated HIV viral burden in already virologically suppressed patients.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11576/2639793
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