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

Vibholm, Line K.a,b; Konrad, Christina V.b,*; Schleimann, Mariane H.a,*; Frattari, Giacomoa,*; Winckelmann, Annia,*; Klastrup, Vibekea; Jensen, Nanna M.a; Jensen, Sanne S.a; Schmidt, Manuelc; Wittig, Burghardtc,d; Zuwala, Kajaa; Mack, Katharinab; Olesen, Rikkeb; Hua, Stephanee; Lichterfeld, Mathiase; Østergaard, Larsa,b; Denton, Paul W.a,b; Tolstrup, Martina,b; Søgaard, Ole S.a,b

doi: 10.1097/QAD.0000000000002213

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; 60 mg × 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 > 5000 copies/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; NCT02443935.

aDepartment of Infectious Diseases, Aarhus University Hospital

bInstitute of Clinical Medicine, Aarhus University, Aarhus, Denmark

cMologen AG

dMolBio2Math - Molecular Biology & Integral Biomathics, Berlin, Germany

eRagon Institute of MGH, MIT and Harvard, Boston, Massachusetts, USA.

Correspondence to Ole S. Søgaard, MD, Department of Infectious Diseases, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200 Aarhus N, Denmark. E-mail:

Received 22 January, 2019

Revised 21 February, 2019

Accepted 22 February, 2019

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Copyright © 2019 Wolters Kluwer Health, Inc.