title: Dysregulated Immune Activation in Second-Line HAART HIV+ Patients Is Similar to That of Untreated Patients.
abstract: BACKGROUND
  Successful highly active antiretroviral therapy (HAART) has changed the outcome of AIDS patients worldwide because the complete suppression of viremia improves health and prolongs life expectancy of HIV-1+ patients. However, little attention has been given to the immunological profile of patients under distinct HAART regimens. This work aimed to investigate the differences in the immunological pattern of HIV-1+ patients under the first- or second-line HAART in Brazil.
  
  
  METHODS
  CD4+ T cell counts, Viral load, and plasma concentration of sCD14, sCD163, MCP-1, RANTES, IP-10, IL-1β, IL-6, TNF-α, IL-12, IFN-α, IFN-γ, IL-4, IL-5, and IL-10 were assessed for immunological characterization of the following clinical groups: Non-infected individuals (NI; n = 66), HIV-1+ untreated (HIV; n = 46), HIV-1+ treated with first-line HAART (HAART 1; n = 15); and HIV-1+ treated with second-line HAART (HAART 2; n = 15).
  
  
  RESULTS
  We found that the immunological biosignature pattern of HAART 1 is similar to that of NI individuals, especially in patients presenting slow progression of the disease, while patients under HAART 2 remain in a moderate inflammatory state, which is similar to that of untreated HIV patients pattern. Network correlations revealed that differences in IP-10, TNF-α, IL-6, IFN-α, and IL-10 interactions were primordial in HIV disease and treatment. Heat map and decision tree analysis identified that IP-10>TNF-α>IFN-α were the best respective HAART segregation biomarkers.
  
  
  CONCLUSIONS
  HIV patients in different HAART regimens develop distinct immunological biosignature, introducing a novel perspective into disease outcome and potential new therapies that consider HAART patients as a heterogeneous group.
authors.affiliation: Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Milena S
authors.initials: MS
authors.lastname: Espíndola
authors.affiliation: Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Leonardo J G
authors.initials: LJ
authors.lastname: Lima
authors.affiliation: Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Luana S
authors.initials: LS
authors.lastname: Soares
authors.affiliation: Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Maira C
authors.initials: MC
authors.lastname: Cacemiro
authors.affiliation: Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Fabiana A
authors.initials: FA
authors.lastname: Zambuzi
authors.affiliation: Laboratorio de Bioinformatica e Analises Moleculares - INGEB / FACOM, Universidade Federal de Uberlandia, Patos de Minas, MG, Brazil.
authors.forename: Matheus
authors.initials: M
authors.lastname: de Souza Gomes
authors.affiliation: Laboratorio de Bioinformatica e Analises Moleculares - INGEB / FACOM, Universidade Federal de Uberlandia, Patos de Minas, MG, Brazil.
authors.forename: Laurence R
authors.initials: LR
authors.lastname: Amaral
authors.affiliation: Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Valdes R
authors.initials: VR
authors.lastname: Bollela
authors.affiliation: Laboratorio de Biomarcadores para Diagnostico e Monitoramento, Centro de Pesquisas Rene Rachou, FIOCRUZ, Belo Horizonte, MG, Brazil.
authors.forename: Olindo A
authors.initials: OA
authors.lastname: Martins-Filho
authors.affiliation: Faculdade de Ciencias Farmaceuticas de Ribeirao Preto, Universidade de Sao Paulo, Ribeirao Preto, SP, Brazil.
authors.forename: Fabiani G
authors.initials: FG
authors.lastname: Frantz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019562:Viral Load; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D016207:Cytokines