Background: Longitudinal characterization of immune recovery in the first-phase of antiretroviral therapy (ART) is poorly described. We compared immune kinetics in individuals who were diagnosed early or late with HIV-1 infection, (thus commencing ART with different CD4+ T-cell counts), in order to investigate possible mechanisms involved in subsequent poor immune recovery. Methods: Immunophenotyping, immune activation, proliferation, apoptosis, regulatory T-cells and intracellular cytokine production were compared at baseline and during 24-week follow-up in two groups of HIV-1-infected patients initiating the same ART (tenofovir/emtricitabine/efavirenz) and divided according to baseline CD4+ T-cell counts (late: ≤200/μL; early: >200/μL). Wilcoxon-rank sum test and analysis for repeated measures were used to evaluate differences between groups over time. Results: Twenty-four out of 30 enrolled subjects were evaluable for the analysis, 13 late and 11 early presenters. Significantly lower CD4+ naïve and memory T-cells, and higher plasma viral load, as well as augmented percentages of activated (CD4+/CD25+ cells), apoptotic (CD4+/AnnexinV+/7AAD-, CD4+/caspase 8+ and CD4+/caspase 9+), and proliferating (CD8+/Ki67+ cells) lymphocytes were present at baseline in late presenters; ART resulted in a reduction of apoptotic and proliferating lymphocytes within the follow-up period. Conclusions: A skewing towards memory/activated/apoptotic phenotype is seen in HIV-1-infected subjects starting ART at low CD4+ T-cell counts; ART results in early (24 weeks) trend towards normalization of these parameters. Antiretroviral therapy may play a role in rapidly limiting aberrant immune exhaustion even in late presenters, while requiring more time for repopulation of highly depleted naïve T-cells. Trial Registration: EU Clinical Trial Register EUDRACT number 2008-006188-35 https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-006188-35/IT.

Soria, A., Trabattoni, D., Squillace, N., Rainone, V., Gnudi, F., Clerici, M., et al. (2015). Prospective immune dynamics during the first 24 weeks of efavirenz based-antiretroviral therapy in HIV-1-infected subjects, according to CD4+ T-cell counts at presentation: The IMMUNEF clinical trial. PLOS ONE, 10(2) [10.1371/journal.pone.0117118].

Prospective immune dynamics during the first 24 weeks of efavirenz based-antiretroviral therapy in HIV-1-infected subjects, according to CD4+ T-cell counts at presentation: The IMMUNEF clinical trial

SORIA, ALESSANDRO
Primo
;
SQUILLACE, NICOLA;GORI, ANDREA
Penultimo
;
BANDERA, ALESSANDRA
Ultimo
2015

Abstract

Background: Longitudinal characterization of immune recovery in the first-phase of antiretroviral therapy (ART) is poorly described. We compared immune kinetics in individuals who were diagnosed early or late with HIV-1 infection, (thus commencing ART with different CD4+ T-cell counts), in order to investigate possible mechanisms involved in subsequent poor immune recovery. Methods: Immunophenotyping, immune activation, proliferation, apoptosis, regulatory T-cells and intracellular cytokine production were compared at baseline and during 24-week follow-up in two groups of HIV-1-infected patients initiating the same ART (tenofovir/emtricitabine/efavirenz) and divided according to baseline CD4+ T-cell counts (late: ≤200/μL; early: >200/μL). Wilcoxon-rank sum test and analysis for repeated measures were used to evaluate differences between groups over time. Results: Twenty-four out of 30 enrolled subjects were evaluable for the analysis, 13 late and 11 early presenters. Significantly lower CD4+ naïve and memory T-cells, and higher plasma viral load, as well as augmented percentages of activated (CD4+/CD25+ cells), apoptotic (CD4+/AnnexinV+/7AAD-, CD4+/caspase 8+ and CD4+/caspase 9+), and proliferating (CD8+/Ki67+ cells) lymphocytes were present at baseline in late presenters; ART resulted in a reduction of apoptotic and proliferating lymphocytes within the follow-up period. Conclusions: A skewing towards memory/activated/apoptotic phenotype is seen in HIV-1-infected subjects starting ART at low CD4+ T-cell counts; ART results in early (24 weeks) trend towards normalization of these parameters. Antiretroviral therapy may play a role in rapidly limiting aberrant immune exhaustion even in late presenters, while requiring more time for repopulation of highly depleted naïve T-cells. Trial Registration: EU Clinical Trial Register EUDRACT number 2008-006188-35 https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-006188-35/IT.
No
Articolo in rivista - Articolo scientifico
Scientifica
Agricultural and Biological Sciences (all); Biochemistry, Genetics and Molecular Biology (all); Medicine (all)
English
Soria, A., Trabattoni, D., Squillace, N., Rainone, V., Gnudi, F., Clerici, M., et al. (2015). Prospective immune dynamics during the first 24 weeks of efavirenz based-antiretroviral therapy in HIV-1-infected subjects, according to CD4+ T-cell counts at presentation: The IMMUNEF clinical trial. PLOS ONE, 10(2) [10.1371/journal.pone.0117118].
Soria, A; Trabattoni, D; Squillace, N; Rainone, V; Gnudi, F; Clerici, M; Gori, A; Bandera, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/10281/96661
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