title: Visceral leishmaniasis as an independent cause of high immune activation, T-cell senescence, and lack of immune recovery in virologically suppressed HIV-1-coinfected patients.
abstract: OBJECTIVE
  Different immune alterations have been described in HIV-infected patients with visceral leishmaniasis (VL). We aimed to identify the immunological factors involved in the lack of immunological recovery and VL relapses in HIV-infected patients with VL, by comparison with other HIV-infected patients.
  
  
  METHODS
  We carried out a cross-sectional study of 55 patients receiving suppressive combination antiretroviral therapy (cART) for at least 1 year: nine with previous relapsing VL, 20 with an immunodiscordant response (IDR) to cART (CD4 count < 200 cells/μL) and no previous VL, and 26 with a concordant response (CR) to cART (CD4 count > 350 cells/μL) without VL. Immunosenescence was investigated by analysing CD57(+) CD28(-) levels, immune activation by analysing CD38(+) HLA-DR(+) levels, inflammation by analysing interleukin (IL)-6 levels, and microbial translocation by analysing lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels.
  
  
  RESULTS
  In VL patients, the median time since VL diagnosis was 42 months, and all patients had had at least one relapse despite suppressive cART for a median time of 43 months. Patients with previously diagnosed VL had a higher CD8 T-cell activation level (P < 0.001) than those with IDR. Also, levels of IL-6, LPS and especially sCD14, associated with bacterial translocation and additional monocyte activation, were significantly increased in patients with previous VL compared with patients with IDR (P = 0.048, P = 0.049 and P < 0.001, respectively). In addition, patients with previous VL had higher levels of CD8 T-cell senescence. Notably, the levels of immune activation and inflammation in patients with previous VL were not related to the time of VL diagnosis, the number of VL relapses, or hepatitis C virus (HCV) coinfection.
  
  
  CONCLUSIONS
  Our data demonstrate that VL patients had an even worse immunological status than patients with IDR, which was probably associated with increased microbial translocation and additional monocyte/macrophage activation. These data explain the observed lack of immunological recovery and the occurrence of VL relapses in HIV-infected patients with previous VL.
authors.affiliation: Department of Infectious Diseases, Ramon y Cajal Hospital, Madrid, Spain.
authors.forename: J L
authors.initials: JL
authors.lastname: Casado
authors.forename: M
authors.initials: M
authors.lastname: Abad-Fernández
authors.forename: S
authors.initials: S
authors.lastname: Moreno
authors.forename: M J
authors.initials: MJ
authors.lastname: Pérez-Elías
authors.forename: A
authors.initials: A
authors.lastname: Moreno
authors.forename: J I
authors.initials: JI
authors.lastname: Bernardino
authors.forename: A
authors.initials: A
authors.lastname: Vallejo
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D016922:Cellular Senescence / Q000276:immunology*; D060085:Coinfection; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D015658:HIV Infections / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D006801:Humans; D007249:Inflammation / Q000276:immunology* / Q000503:physiopathology; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000401:mortality / Q000503:physiopathology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D013030:Spain / Q000453:epidemiology; D013601:T-Lymphocytes / Q000276:immunology*; D019562:Viral Load
keywords: HIV; immune activation; immunodiscordance; immunosenescence; leishmaniasis