Persistence of pathological distribution of NK cells in HIV-infected patients with prolonged use of HAART and a sustained immune response

PLoS One. 2015 Mar 26;10(3):e0121019. doi: 10.1371/journal.pone.0121019. eCollection 2015.


Objective: A prospective analysis of the distribution of NK subsets and natural cytotoxicity receptors (NKp30/NKp46) in HIV patients with long-term HAART use and sustained virological and immunological response.

Methods: The main inclusion criteria were: at least 3 years' receipt of HAART; current CD4+ count ≥ 500 cells/mm3; undetectable viral load for at least 24 months; no hepatotropic virus co-infection. Percentages of CD56dim, CD56bright NK cells and CD56neg CD16+ cells were obtained. Expression of the NCRs, NKp30 and NKp46 was analysed in CD56+ cells. Thirty-nine infected patients and sixteen healthy donors were included in the study.

Results: The percentages of total CD56+ and CD56dim NK cells were significantly lower in HIV-infected patients than in healthy donors (70.4 vs. 50.3 and 80.9 vs. 66.1 respectively). The percentage of total CD56+ NK cells expressing NCR receptors was lower in HIV patients than in healthy donors (NKp30: 25.20 vs. 58.63; NKp46: 24.8 vs. 50.59). This was also observed for CD56dim and CD56bright NK cells. Length of time with undetectable HIV viral load was identified as an independent factor associated with higher expression of NKp30 and NKp46.

Conclusion: Despite the prolonged and effective use of HAART, HIV-infected patients do not fully reconstitute the distribution of NK cells. Length of time with an undetectable viral load was related to greater recovery of NKp30/NKp46 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active*
  • Female
  • Flow Cytometry
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • Humans
  • Immunity*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / pathology*
  • Linear Models
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Natural Cytotoxicity Triggering Receptor 1 / metabolism
  • Natural Cytotoxicity Triggering Receptor 3 / metabolism
  • Tissue Donors
  • Viral Load


  • Natural Cytotoxicity Triggering Receptor 1
  • Natural Cytotoxicity Triggering Receptor 3

Grant support

The study was funded by Fundación Progreso y Salud, Consejería de Salud de la Junta de Andalucía (grants for health research projects: refs. PI-0430/2012; PI-0247/2010; PI-0208/2008; PI-0124/2008; PI-0305/2009). AR has received a Research Extension Grant from the Consejería de Salud, Innovación y Ciencia de la Junta de Andalucía. ARJ is the recipient of a post-doctoral perfection grant, in the recently-qualified doctors category, from the Consejería de Igualdad, Salud y Políticas Sociales (RH-0024-2013). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.