title: Effects of combined antiretroviral therapy on B- and T-cell release from production sites in long-term treated HIV-1+ patients.
abstract: BACKGROUND
  The immune system reconstitution in HIV-1- infected patients undergoing combined antiretroviral therapy is routinely evaluated by T-cell phenotyping, even though the infection also impairs the B-cell mediated immunity. To find new laboratory markers of therapy effectiveness, both B- and T- immune recovery were evaluated by means of a follow-up study of long-term treated HIV-1- infected patients, with a special focus on the measure of new B- and T-lymphocyte production.
  
  
  METHODS
  A longitudinal analysis was performed in samples obtained from HIV-1-infected patients before therapy beginning and after 6, 12, and 72 months with a duplex real-time PCR allowing the detection of K-deleting recombination excision circles (KRECs) and T-cell receptor excision circles (TRECs), as measures of bone-marrow and thymic output, respectively. A cross sectional analysis was performed to detect B- and T-cell subsets by flow cytometry in samples obtained at the end of the follow-up, which were compared to those of untreated HIV-1-infected patients and uninfected controls.
  
  
  RESULTS
  The kinetics and the timings of B- and T-cell release from the bone marrow and thymus during antiretroviral therapy were substantially different, with a decreased B-cell release and an increased thymic output after the prolonged therapy. The multivariable regression analysis showed that a longer pre-therapy infection duration predicts a minor TREC increase and a major KREC reduction.
  
  
  CONCLUSIONS
  The quantification of KRECs and TRECs represents an improved method to monitor the effects of therapies capable of influencing the immune cell pool composition in HIV-1-infected patients.
authors.affiliation: Laboratory of Biotechnology, Diagnostics Department, Spedali Civili of Brescia, Brescia, Italy.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Quiros-Roldan
authors.forename: Federico
authors.initials: F
authors.lastname: Serana
authors.forename: Marco
authors.initials: M
authors.lastname: Chiarini
authors.forename: Cinzia
authors.initials: C
authors.lastname: Zanotti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Sottini
authors.forename: Daria
authors.initials: D
authors.lastname: Gotti
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.forename: Luigi
authors.initials: L
authors.lastname: Caimi
authors.forename: Luisa
authors.initials: L
authors.lastname: Imberti
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D017931:DNA Primers; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D006801:Humans; D015851:Interleukin-7 / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D020395:Receptors, Interleukin-7 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D019380:Anti-HIV Agents; D017931:DNA Primers; D015851:Interleukin-7; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain