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

Alessandro Soria, Daria Trabattoni, Nicola Squillace, Veronica Rainone, Federica Gnudi, Mario Clerici, Andrea Gori, Alessandra Bandera

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish
Article numbere0117118
JournalPLoS One
Volume10
Issue number2
DOIs
Publication statusPublished - Feb 11 2015

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efavirenz
T-cells
CD4 Lymphocyte Count
Human immunodeficiency virus 1
HIV-1
clinical trials
T-lymphocytes
Clinical Trials
T-Lymphocytes
therapeutics
Tenofovir
Lymphocytes
Nonparametric Statistics
Therapeutics
Play Therapy
lymphocytes
Data storage equipment
Recovery
Immunophenotyping
Caspase 9

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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; Trabattoni, Daria; Squillace, Nicola; Rainone, Veronica; Gnudi, Federica; Clerici, Mario; Gori, Andrea; Bandera, Alessandra.

In: PLoS One, Vol. 10, No. 2, e0117118, 11.02.2015.

Research output: Contribution to journalArticle

Soria, Alessandro ; Trabattoni, Daria ; Squillace, Nicola ; Rainone, Veronica ; Gnudi, Federica ; Clerici, Mario ; Gori, Andrea ; Bandera, Alessandra. / 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. In: PLoS One. 2015 ; Vol. 10, No. 2.
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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+ na{\"i}ve 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 na{\"i}ve T-cells. Trial Registration: EU Clinical Trial Register EUDRACT number 2008-006188-35 https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-006188-35/IT.",
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AU - Trabattoni, Daria

AU - Squillace, Nicola

AU - Rainone, Veronica

AU - Gnudi, Federica

AU - Clerici, Mario

AU - Gori, Andrea

AU - Bandera, Alessandra

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N2 - 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.

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