Toll-like Receptor 9 Agonist Treatment in Chronic HIV-1 Infection

Summary

Combination antiretroviral treatment (cART) effectively suppresses virus replication and partially restores immune functions. However, cART cannot cure HIV infection. This study aim to investigate whether the antiviral immune response can be enhanced and/or viral transcription reactivated with MGN1703. MGN1703 is an agonist to toll-like receptor (TLR) 9. Activation of TLR9 has been shown to augment innate and adaptive immune effector functions, most notably enhanced NK cell and T cell functions. Furthermore, TLR9 agonists have been shown in vitro to reactivate viral transcription in latently infected cells, potentially leading to enhanced recognition of infected cells by the immune effector cells.

Timeline

Start

2015-04

Primary completion

2017-06-01

Completion

2017-06-25

Publications

• Vibholm LK, Konrad CV, Schleimann MH, Frattari G, Winckelmann A, Klastrup V, Jensen NM, Jensen SS, Schmidt M, Wittig B, Zuwala K, Mack K, Olesen R, Hua S, Lichterfeld M, Ostergaard L, Denton PW, Tolstrup M, Sogaard OS. Effects of 24-week Toll-like receptor 9 agonist treatment in HIV type 1+ individuals. AIDS. 2019 Jul 1;33(8):1315-1325. doi: 10.1097/QAD.0000000000002213.
• Vibholm L, Schleimann MH, Hojen JF, Benfield T, Offersen R, Rasmussen K, Olesen R, Dige A, Agnholt J, Grau J, Buzon M, Wittig B, Lichterfeld M, Petersen AM, Deng X, Abdel-Mohsen M, Pillai SK, Rutsaert S, Trypsteen W, De Spiegelaere W, Vandekerchove L, Ostergaard L, Rasmussen TA, Denton PW, Tolstrup M, Sogaard OS. Short-Course Toll-Like Receptor 9 Agonist Treatment Impacts Innate Immunity and Plasma Viremia in Individuals With Human Immunodeficiency Virus Infection. Clin Infect Dis. 2017 Jun 15;64(12):1686-1695. doi: 10.1093/cid/cix201.

Drugs

Indications