Combination anti-PD-1 and antiretroviral therapy provides therapeutic benefit against SIV

Geetha H. Mylvaganam, Lynette S. Chea, Gregory K. Tharp, Sakeenah Hicks, Vijayakumar Velu, Smita Iyer, Claire Deleage, Jacob D. Estes, Steven E. Bosinger, Gordon J. Freeman, Rafi Ahmed, Rama R. Amara

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Therapeutic strategies that augment antiviral immunity and reduce the viral reservoir are critical to achieving durable remission of HIV. The coinhibitory receptor programmed death-1 (PD-1) regulates CD8+ T cell dysfunction during chronic HIV and SIV infections. We previously demonstrated that in vivo blockade of PD-1 during chronic SIV infection improves the function of antiviral CD8+ T cells and B cells. Here, we tested the immunological and virological effects of PD-1 blockade combined with antiretroviral therapy (ART) in rhesus macaques. Administration of anti-PD-1 antibody 10 days prior to ART initiation rapidly enhanced antiviral CD8+ T cell function and diminished IFN-stimulated genes. This resulted in faster viral suppression in plasma and better Th17 cell reconstitution in the rectal mucosa following ART initiation. PD-1 blockade during ART resulted in lower levels of cell-associated replication-competent virus. Following ART interruption, PD-1 antibody-treated animals showed markedly higher expansion of proliferating CXCR5+perforin+granzyme B+ effector CD8+ T cells and lower regulatory T cells that resulted in better control of viremia. Our results show that PD-1 blockade can be administered safely with ART to augment antiviral CD8+ T cell function and reduce the viral reservoir, leading to improved control of viral rebound after ART interruption.

Original languageEnglish (US)
JournalJCI insight
Volume3
Issue number18
DOIs
StatePublished - Sep 20 2018
Externally publishedYes

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Antiviral Agents
T-Lymphocytes
Therapeutics
Th17 Cells
Death Domain Receptors
Antibodies
Viremia
Regulatory T-Lymphocytes
Virus Replication
Macaca mulatta
HIV Infections
Immunity
Mucous Membrane
B-Lymphocytes
HIV
Infection
Genes

Keywords

  • AIDS/HIV
  • Immunology
  • Immunotherapy

Cite this

Mylvaganam, G. H., Chea, L. S., Tharp, G. K., Hicks, S., Velu, V., Iyer, S., ... Amara, R. R. (2018). Combination anti-PD-1 and antiretroviral therapy provides therapeutic benefit against SIV. JCI insight, 3(18). https://doi.org/10.1172/jci.insight.122940

Combination anti-PD-1 and antiretroviral therapy provides therapeutic benefit against SIV. / Mylvaganam, Geetha H.; Chea, Lynette S.; Tharp, Gregory K.; Hicks, Sakeenah; Velu, Vijayakumar; Iyer, Smita; Deleage, Claire; Estes, Jacob D.; Bosinger, Steven E.; Freeman, Gordon J.; Ahmed, Rafi; Amara, Rama R.

In: JCI insight, Vol. 3, No. 18, 20.09.2018.

Research output: Contribution to journalArticle

Mylvaganam, GH, Chea, LS, Tharp, GK, Hicks, S, Velu, V, Iyer, S, Deleage, C, Estes, JD, Bosinger, SE, Freeman, GJ, Ahmed, R & Amara, RR 2018, 'Combination anti-PD-1 and antiretroviral therapy provides therapeutic benefit against SIV', JCI insight, vol. 3, no. 18. https://doi.org/10.1172/jci.insight.122940
Mylvaganam, Geetha H. ; Chea, Lynette S. ; Tharp, Gregory K. ; Hicks, Sakeenah ; Velu, Vijayakumar ; Iyer, Smita ; Deleage, Claire ; Estes, Jacob D. ; Bosinger, Steven E. ; Freeman, Gordon J. ; Ahmed, Rafi ; Amara, Rama R. / Combination anti-PD-1 and antiretroviral therapy provides therapeutic benefit against SIV. In: JCI insight. 2018 ; Vol. 3, No. 18.
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