Open AccessShort Communication: Metformin Reduces CD4 T Cell Exhaustion in HIV-Infected Adults on Suppressive Antiretroviral Therapy
Author(s) -
Cecilia Shikuma,
Glen M. Chew,
Lindsay Kohorn,
Scott Souza,
Dominic Chow,
Ivo N. SahBandar,
EunYoung Park,
Nancy Hanks,
Louie Mar A. Gangcuangco,
Mariana Gerschenson,
Lishomwa C. Ndhlovu
Publication year - 2020
Publication title -
aids research and human retroviruses
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.993
H-Index - 92
eISSN - 1931-8405
pISSN - 0889-2229
DOI - 10.1089/aid.2019.0078
Subject(s) - tigit , metformin , medicine , cd8 , cd38 , cytotoxic t cell , immunology , t cell , immune system , biology , insulin , microbiology and biotechnology , cd34 , biochemistry , stem cell , in vitro
Increased negative immune checkpoint receptors (NCR) on T cells are linked to T cell exhaustion, dysfunctional effector responses, and HIV viral persistence. Metformin, an oral hypoglycemic agent used for diabetes, may have previously unrecognized beneficial immunologic effects. Using cryopreserved blood from a 24-week pilot study involving 12 virally suppressed HIV-infected individuals randomized 1:1 to metformin versus observation (OBS), we assessed change in the frequencies of T cell activation (CD38 + HLA-DR + ) and NCR [programmed cell death protein 1 (PD1), T cell immunoreceptor with Ig and ITIM domains (TIGIT), and T cell mucin-domain containing-3 (TIM3)]. No differences in 24-week change were seen between arms in CD4 or CD8 T cells, in the CD4/CD8 ratio, or in activated (CD38 + HLA-DR + ) CD4 or CD8 T cells. However, metformin over 24 weeks led to decreases compared with OBS in single PD1 + (percent decrease: -9.6% vs. 7.5%, p = .015), in dual PD1 + TIGIT + (-15.0% vs. 10.4%, p = .002), and in triple PD1 + TIGIT + TIM3 + (-24.0% vs. 8.1%, p = .041) CD4 T cells. Metformin led to no changes in CD8 T cell NCR frequencies. Metformin decreases the frequency of PD1 + , PD1 + TIGIT + , and PD1 + TIGIT + TIM3 + expressing CD4 T cells. This may have relevance to HIV cure strategies and to efforts to mitigate the risk of chronic complications of HIV.