Publications & Reports

Persistence of activated and adaptive-like NK cells in HIV+ individuals despite 2 Years of suppressive combination antiretroviral therapy.

Hearps AC, Agius PA, Zhou J, Brunt S, Chachage M, Angelovich TA, Cameron PU, Giles M, Price P, Elliott J, Jaworowski A


Innate immune dysfunction persists in HIV+ individuals despite effective combination antiretroviral therapy (cART). We recently demonstrated that an adaptive-like CD56dim NK cell population lacking the signal transducing protein FcRγ is expanded in HIV+ individuals. Here, we analyzed a cohort of HIV+ men who have sex with men (MSM, n = 20) at baseline and following 6, 12, and 24 months of cART and compared them with uninfected MSM (n = 15) to investigate the impact of cART on NK cell dysfunction. Proportions of NK cells expressing markers of early (CD69+) and late (HLA-DR+/CD38+) activation were elevated in cART-naïve HIV+ MSM (p = 0.004 and 0.015, respectively), as were FcRγ- NK cells (p = 0.003). Using latent growth curve modeling, we show that cART did not reduce levels of FcRγ- NK cells (p = 0.115) or activated HLA-DR+/CD38+ NK cells (p = 0.129) but did reduce T cell and monocyte activation (p < 0.001 for all). Proportions of FcRγ- NK cells were not associated with NK cell, T cell, or monocyte activation, suggesting different factors drive CD56dim FcRγ- NK cell expansion and immune activation in HIV+ individuals. While proportions of activated CD69+ NK cells declined significantly on cART (p = 0.003), the rate was significantly slower than the decline of T cell and monocyte activation, indicating a reduced potency of cART against NK cell activation. Our findings indicate that 2 years of suppressive cART have no impact on CD56dim FcRγ- NK cell expansion and that NK cell activation persists after normalization of other immune parameters. This may have implications for the development of malignancies and co-morbidities in HIV+ individuals on cART.

Link to publisher’s web site

This work was supported by a Project Grant (#1048536) from the National Health and Medical Research Council of Australia awarded to AJ. Funding for establishment of the Melbourne HIV Cohort was provided by Monash University, the Burnet Institute and the Alfred Hospital, Melbourne, Australia.


  • Journal: Frontiers in Immunology
  • Published: 30/06/2017
  • Volume: 8
  • Pagination: 731