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.
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.
  
  
  BACKGROUND
  EU Clinical Trial Register EUDRACT number 2008-006188-35 https://www.clinicaltrialsregister.eu/ctr-search/trial/2008-006188-35/IT.
authors: Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors: Alessandro
authors: A
authors: Soria
authors: Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy.
authors: Daria
authors: D
authors: Trabattoni
authors: Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors: Nicola
authors: N
authors: Squillace
authors: Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy.
authors: Veronica
authors: V
authors: Rainone
authors: Department of Biomedical and Clinical Sciences L. Sacco, University of Milan, Milan, Italy.
authors: Federica
authors: F
authors: Gnudi
authors: Department of Physiopathology and Transplants, University of Milan, Milan, Italy; Don Carlo Gnocchi Foundation, IRCCS, Milan, Italy.
authors: Mario
authors: M
authors: Clerici
authors: Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors: Andrea
authors: A
authors: Gori
authors: Division of Infectious Diseases, Department of Internal Medicine, San Gerardo Hospital, University of Milano-Bicocca, Monza, Italy.
authors: Alessandra
authors: A
authors: Bandera
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D048588:Benzoxazines / Q000494:pharmacology* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz