Short Communication: Metformin Reduces CD4 T Cell Exhaustion in HIV-Infected Adults on Suppressive Antiretroviral Therapy.
AIDS Res Hum Retroviruses
; 36(4): 303-305, 2020 04.
Article
em En
| MEDLINE
| ID: mdl-31731885
ABSTRACT
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 11 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
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4_TD
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Infecções por HIV
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Proteínas de Checkpoint Imunológico
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Metformina
Tipo de estudo:
Clinical_trials
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
AIDS Res Hum Retroviruses
Ano de publicação:
2020
Tipo de documento:
Article