The TLR7 agonist vesatolimod induced a modest delay in viral rebound in HIV controllers after cessation of antiretroviral therapy.
Devi SenGuptaCynthia BrinsonEdwin DeJesusAnthony MillsPeter ShalitSusan GuoYanhui CaiJeffrey J WallinLiao ZhangRita HumeniukRebecca BegleyRomas GeleziunasJohn W MellorsTerri WrinNorman JonesJeffrey MilushApril L FerreBarbara L ShacklettGregory M LairdBrian MoldtElena VendrameDiana M BrainardMoti RamgopalSteven G DeeksPublished in: Science translational medicine (2021)
Toll-like receptor 7 (TLR7) agonists, in combination with other therapies, can induce sustained control of simian-human immunodeficiency virus (SHIV) or simian immunodeficiency virus (SIV) in nonhuman primates. Here, we report the results of a randomized, double-blind, placebo-controlled phase 1b clinical trial of an oral TLR7 agonist, vesatolimod, in HIV-1-infected controllers on antiretroviral therapy (ART). We randomized participants 2:1 to receive vesatolimod (n = 17) or placebo (n = 8) once every other week for a total of 10 doses while continuing on ART. ART was then interrupted, and the time to viral rebound was analyzed using the Kaplan-Meier method. Vesatolimod was associated with induction of immune cell activation, decreases in intact proviral DNA during ART, and a modest increase in time to rebound after ART was interrupted. The delayed viral rebound was predicted by the lower intact proviral DNA at the end of vesatolimod treatment (13 days after the final dose). Inferred pathway analysis suggested increased dendritic cell and natural killer cell cross-talk and an increase in cytotoxicity potential after vesatolimod dosing. Larger clinical studies will be necessary to assess the efficacy of vesatolimod-based combination therapies aimed at long-term control of HIV infection.
Keyphrases
- antiretroviral therapy
- hiv infected
- toll like receptor
- human immunodeficiency virus
- double blind
- placebo controlled
- clinical trial
- hiv positive
- hiv infected patients
- phase iii
- inflammatory response
- hiv aids
- phase ii
- nuclear factor
- immune response
- sars cov
- phase ii study
- study protocol
- randomized controlled trial
- dendritic cells
- circulating tumor
- stem cells
- diabetic rats
- oxidative stress
- human health
- open label
- single cell
- smoking cessation
- single molecule
- stress induced
- hepatitis c virus