title: Structured Treatment Interruptions and Low Doses of IL-2 in Patients with Primary HIV Infection. Inflammatory, Virological and Immunological Outcomes.
abstract: BACKGROUND
  Interventions during primary HIV infection (PHI) can modify the clinical course during the chronic phase. The long-term effect of structured treatment interruptions (STI) followed by low doses of interleukin-2 (IL-2) in treated PHI patients is unknown.
  
  
  METHODS
  Twelve PHI patients with viral load (VL) <20 copies/mL, CD4 cells >500 cells/mm3, and CD4/CD8 ratio >1, on antiretroviral therapy (ART) initiated within the first 90 days of infection and continued for at least 12 months were included. They underwent four STI and were then allocated (week 0 of the study) to ART alone or ART plus low doses of IL-2. ART was stopped once VL <20 copies/mL ('final stop'). Primary endpoints were VL<3000 copies/mL and CD4 cells >500 cells/mm3 at 48 weeks; secondary endpoints were immune activation, inflammatory markers until 48 weeks and the time before resuming ART (CD4 <350 cells/mm3 or AIDS) after 'final stop', compared between groups.
  
  
  RESULTS
  Ten out of 12 patients were males, median age was 35 years and the main risk was men-who-have-sex-with-men. Only one out of 12 patients (in the STI group) maintained VL<3000 copies/mL and CD4 cells >500 cells/mm3 without ART at 48 weeks. All other virological and immunological parameters were comparable between groups at week 0, 'final stop' and week 48. However, the proportion of CD8-CD38+ cells, tumor necrosis factor and srIL-2 were higher in the IL-2 group at 'final stop' and week 24. All these differences vanished during follow-up. At 5 years after the final stop 3 out of 6 patients in the IL-2 group and 6 out of 6 patients in the STI group have resumed ART (P = 0.19).
  
  
  CONCLUSIONS
  STI and IL-2 failed to achieve virological control after ART interruption. STI were not deleterious in long-term follow-up, an important issue for eradication and functional cure trials.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT02300623.
authors.affiliation: Infectious Diseases Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Omar
authors.initials: O
authors.lastname: Sued
authors.affiliation: Infectious Diseases Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Ambrosioni
authors.affiliation: Infectious Diseases Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Nicolás
authors.affiliation: Infectious Diseases Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Christian
authors.initials: C
authors.lastname: Manzardo
authors.affiliation: Infectious Diseases Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Agüero
authors.affiliation: Infectious Diseases Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Claramonte
authors.affiliation: Infectious Diseases Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.affiliation: Pharmacy Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Tuset
authors.affiliation: Infectious Diseases Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Tomás
authors.initials: T
authors.lastname: Pumarola
authors.affiliation: Infectious Diseases Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
authors.affiliation: Infectious Diseases Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Gatell
authors.affiliation: Infectious Diseases Service, Hospital Clínic-IDIBAPS, University of Barcelona, Barcelona, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Miró
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D008297:Male; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D007376:Interleukin-2