Publications & Posters

Vesatolimod, A Toll-like Receptor 7 Agonist, Induces Immune Activation In Virally Suppressed Adults With HIV-1

Clinical Infectious Diseases : An Official Publication Of The Infectious Diseases Society Of America | October 12, 2020

Riddler SA, Para M, Benson CA, Mills A, Ramgopal M, DeJesus E, Brinson C, Cyktor J, Jacobs J, Koontz D, Mellors J, Laird GM, Wrin T, Patel H, Guo S, Wallin J, Boice J, Zhang L, Humeniuk R, Begley R, German P, Graham H, Geleziunas R, Brainard DM and SenGupta D

Clin Infect Dis. 2020 Oct 12;ciaa1534




Treatment with vesatolimod, an investigational oral toll-like receptor 7 (TLR7) agonist, leads to sustained viral remission in some non-human primates when combined with anti-envelope antibodies or therapeutic vaccines. We report results of a phase 1 study evaluating safety, pharmacokinetics, and pharmacodynamics of vesatolimod in adults living with HIV-1.


In this double-blind, multicentre, placebo-controlled trial ( NCT02858401), participants on antiretroviral therapy with screening plasma HIV-1 RNA levels <50 copies/mL were randomized (6:2) to receive 6-10 doses of vesatolimod (1-12 mg) or matching placebo orally every other week in sequential dose escalation cohorts. Primary study objectives included safety and virologic effects of vesatolimod (change from baseline in plasma HIV-1 RNA). Pharmacokinetics and pharmacodynamic/immunologic activity were assessed as secondary objectives.


A total of 48 individuals were randomly assigned to vesatolimod (n=36) or placebo (n=12). Vesatolimod was generally well tolerated with no study drug-related serious adverse events or adverse events leading to study discontinuation. There were no statistically significant changes from baseline in plasma HIV-1 RNA in the vesatolimod groups compared to placebo.

Vesatolimod plasma exposures increased dose-proportionally; consistent responses in cytokines, interferon-stimulated gene expression, and lymphocyte activation were observed with increasing dose levels above 4 mg. Peak elevations 24 hours post 6 mg dose were >3·9-fold for IP-10, IL-1Ra, and ITAC when compared to baseline values.


Vesatolimod was well tolerated at doses ranging from 1 to 12 mg. Immune stimulation observed at doses above 4 mg, providing rationale for future combination trials in people with HIV.