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  • Title: 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.
    Author: Soria A, Trabattoni D, Squillace N, Rainone V, Gnudi F, Clerici M, Gori A, Bandera A.
    Journal: PLoS One; 2015; 10(2):e0117118. PubMed ID: 25671649.
    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 re-population 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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