Dysregulated Immune Activation in Second-Line HAART HIV+ Patients Is Similar to That of Untreated Patients

PLoS One. 2015 Dec 18;10(12):e0145261. doi: 10.1371/journal.pone.0145261. eCollection 2015.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Biomarkers / blood
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Cytokines / blood
  • Disease Progression
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / immunology*
  • HIV-1 / immunology*
  • Humans
  • Male
  • Middle Aged
  • Viral Load
  • Young Adult

Substances

  • Anti-HIV Agents
  • Biomarkers
  • Cytokines

Grants and funding

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo, grants: MSE #2011/12512-0; FGF #2011/12199-0; LSS #2011/24026-3; LJGL #2012/02799-3. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.