Effects of 24-week Toll-like receptor 9 agonist treatment in HIV type 1+ individuals

Line K. Vibholm, Christina V. Konrad, Mariane H. Schleimann, Giacomo Frattari, Anni Winckelmann, Vibeke Klastrup, Nanna M. Jensen, Sanne S. Jensen, Manuel Schmidt, Burghardt Wittig, Kaja Zuwala, Katharina Mack, Rikke Olesen, Stephane Hua, Mathias Lichterfeld, Lars Østergaard, Paul W. Denton, Martin Tolstrup, Ole S. Søgaard

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Design:This was an exploratory, single-Arm clinical trial that tested the immune enhancement effects of 24-weeks of Toll-like receptor 9 (TLR9) agonist (MGN1703; Lefitolimod; 60mg×2 weekly) therapy.Methods:We enrolled HIV-1-infected individuals on suppressive combination antiretroviral therapy. Safety was assessed throughout the study. The primary outcome was reduction in total CD4+ T-cell viral DNA levels. Secondary outcomes included safety, detailed immunological and virological analyses, and time to viral rebound (viral load > 5000copies/ml) after randomization into an analytical treatment interruption (ATI).Results:A total of 12 individuals completed the treatment phase and nine completed the ATI. Adverse events were limited and consistent with previous reports for MGN1703. Although the dosing regimen led to potent T-cell activation and increased HIV-1-specific T-cell responses, there were no cohort-wide changes in persistent virus (total CD4+ T cells viral DNA; P=0.34). No difference in time to rebound was observed between the ATI arms (log rank P=0.25). One of nine ATI participants, despite harboring a large replication-competent reservoir, controlled viremia for 150 days via both HIV-1-specific cellular and antibody-mediated immune responses.Conclusion:A period of 24 weeks of MGN1703 treatment was safe and improved innate as well as HIV-1-specific adaptive immunity in HIV-1+ individuals. These findings support the incorporation of TLR9 agonism into combination HIV-1 cure strategies.Trial name and registration:TLR9 Enhancement of antiviral immunity in chronic HIV-1 infection: A phase 1B/2A trial; ClinicalTrials.gov NCT02443935.

Original languageEnglish (US)
Pages (from-to)1315-1325
Number of pages11
JournalAIDS
Volume33
Issue number8
DOIs
StatePublished - Jul 1 2019
Externally publishedYes

Keywords

  • HIV cure
  • HIV type 1
  • MGN1703
  • Toll-like receptor 9 agonist
  • cellular immunity
  • immunotherapy
  • investigational therapy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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