Background and Objective: Despite integrase strand transfer inhibitor (INSTI)-containing regimens now being considered a preferred option for both initial therapy and switching strategies in virologically suppressed patients, their effects on lymphocyte phenotypes and functions in the course of effective combination antiretroviral therapy (cART) are still unclear. Thus, we investigated the effect of a 24-week elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) regimen on the T cell compartment and HIV reservoirs in HIV-infected patients switching from a suppressive protease inhibitor-based regimen. Methods: Thirty HIV-positive patients receiving suppressive tenofovir disoproxil fumarate/emtricitabine (TDF + FTC) (for a median of 5 years) in association with either darunavir/ritonavir (DVR/r) (47%) or atazanavir/ritonavir (ATV/r) (53%) were followed up for 24 weeks after switching to EVG/c/FTC/TDF. At baseline (week 0 [W0]) and after 12 (W12) and 24 (W24) weeks we analyzed HLA-DR (human leukocyte antigen–DR isotype)/CD38/Ki67/CCR7 (C-C chemokine receptor type 7)/CD45RA/CD127/PD-1 (programmed cell death-1) on CD4/CD8, interferon (IFN)-γ/interleukin (IL)-2 after HIV/Staphylococcal enterotoxin B (SEB) exposure (flow cytometry); total, integrated, and unintegrated HIV-DNA; and residual low-level HIV viremia (quantitative polymerase chain reaction [qPCR]). Results: While EVG/c/FTC/TDF introduction resulted in a stable CD4+ and CD8+ count, residual low-level HIV-RNA viremia, and HIV reservoirs, we observed a significant reduction in both activated CD4+ (p = 0.016) and CD8+ (p = 0.048) T cells, coupled with an increase in IL-2 and IFN-γ release by CD4+ and CD8+ effector memory T cells, and a decrease in cytokine production by terminally differentiated CD8+ T cells following SEB exposure. Furthermore, the magnitude of the reduction of activated HLA-DR + CD38 + CD8+ T cells (r = − 0.63, p = 0.014) inversely correlates with the amount of total HIV-DNA at W24. Conclusions: Our data show a favorable effect of EVG/c/FTC/TDF switch to preserve immune activation-driven damage to T cell homeostasis, restore the multifunctional properties of effector T cells, and possibly contain cell-associated HIV viral burden in already virologically suppressed patients.

Reduction of Immune Activation and Partial Recovery of Staphylococcal Enterotoxin B-Induced Cytokine Production After Switching to an Integrase Strand Transfer Inhibitor-Containing Regimen : Results from an Observational Cohort Study / E. Merlini, F.A. Cazzaniga, A. Casabianca, C. Orlandi, M. Magnani, G. Ancona, C. Tincati, A. d'Arminio Monforte, G. Marchetti. - In: CLINICAL DRUG INVESTIGATION. - ISSN 1173-2563. - 39:12(2019), pp. 1239-1249. [10.1007/s40261-019-00840-2]

Reduction of Immune Activation and Partial Recovery of Staphylococcal Enterotoxin B-Induced Cytokine Production After Switching to an Integrase Strand Transfer Inhibitor-Containing Regimen : Results from an Observational Cohort Study

F.A. Cazzaniga;M. Magnani;G. Ancona;C. Tincati;A. d'Arminio Monforte;G. Marchetti
2019

Abstract

Background and Objective: Despite integrase strand transfer inhibitor (INSTI)-containing regimens now being considered a preferred option for both initial therapy and switching strategies in virologically suppressed patients, their effects on lymphocyte phenotypes and functions in the course of effective combination antiretroviral therapy (cART) are still unclear. Thus, we investigated the effect of a 24-week elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) regimen on the T cell compartment and HIV reservoirs in HIV-infected patients switching from a suppressive protease inhibitor-based regimen. Methods: Thirty HIV-positive patients receiving suppressive tenofovir disoproxil fumarate/emtricitabine (TDF + FTC) (for a median of 5 years) in association with either darunavir/ritonavir (DVR/r) (47%) or atazanavir/ritonavir (ATV/r) (53%) were followed up for 24 weeks after switching to EVG/c/FTC/TDF. At baseline (week 0 [W0]) and after 12 (W12) and 24 (W24) weeks we analyzed HLA-DR (human leukocyte antigen–DR isotype)/CD38/Ki67/CCR7 (C-C chemokine receptor type 7)/CD45RA/CD127/PD-1 (programmed cell death-1) on CD4/CD8, interferon (IFN)-γ/interleukin (IL)-2 after HIV/Staphylococcal enterotoxin B (SEB) exposure (flow cytometry); total, integrated, and unintegrated HIV-DNA; and residual low-level HIV viremia (quantitative polymerase chain reaction [qPCR]). Results: While EVG/c/FTC/TDF introduction resulted in a stable CD4+ and CD8+ count, residual low-level HIV-RNA viremia, and HIV reservoirs, we observed a significant reduction in both activated CD4+ (p = 0.016) and CD8+ (p = 0.048) T cells, coupled with an increase in IL-2 and IFN-γ release by CD4+ and CD8+ effector memory T cells, and a decrease in cytokine production by terminally differentiated CD8+ T cells following SEB exposure. Furthermore, the magnitude of the reduction of activated HLA-DR + CD38 + CD8+ T cells (r = − 0.63, p = 0.014) inversely correlates with the amount of total HIV-DNA at W24. Conclusions: Our data show a favorable effect of EVG/c/FTC/TDF switch to preserve immune activation-driven damage to T cell homeostasis, restore the multifunctional properties of effector T cells, and possibly contain cell-associated HIV viral burden in already virologically suppressed patients.
Adult; Anti-HIV Agents; Cohort Studies; Cytokines; Enterotoxins; Female; HIV Infections; HIV Protease Inhibitors; Humans; Male; Middle Aged; T-Lymphocytes
Settore MED/17 - Malattie Infettive
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/827184
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