Poly-ICLC, a TLR3 Agonist, Induces Transient Innate Immune Responses in Patients With Treated HIV-Infection: A Randomized Double-Blinded Placebo Controlled Trial

Front Immunol. 2019 Apr 9;10:725. doi: 10.3389/fimmu.2019.00725. eCollection 2019.


Objective: Toll-like receptor-3 agonist Poly-ICLC has been known to activate immune cells and induce HIV replication in pre-clinical experiments. In this study we investigated if Poly-ICLC could be used for disrupting HIV latency while simultaneously enhancing innate immune responses. Design: This was a randomized, placebo-controlled, double-blinded trial in aviremic, cART-treated HIV-infected subjects. Participants (n = 15) were randomized 3:1 to receive two consecutive daily doses of Poly-ICLC (1.4 mg subcutaneously) vs. placebo. Subjects were observed for adverse events, immune activation, and viral replication. Methods: Besides primary outcomes of safety and tolerability, several longitudinal immune parameters were evaluated including immune cell phenotype and function via flowcytometry, ELISA, and transcriptional profiling. PCR assays for plasma HIV-1 RNA, CD4+ T cell-associated HIV-1 RNA, and proviral DNA were performed to measure HIV reservoirs and latency. Results: Poly-ICLC was overall safe and well-tolerated. Poly-ICLC-related adverse events were Grade 1/2, with the exception of one Grade 3 neutropenia which was short-lived. Mild Injection site reactions were observed in nearly all participants in the Poly-ICLC arm. Transcriptional analyses revealed upregulation of innate immune pathways in PBMCs following Poly-ICLC treatment, including strong interferon signaling accompanied by transient increases in circulating IP-10 (CXCL10) levels. These responses generally peaked by 24-48 h after the first injection and returned to baseline by day 8. CD4+ T cell number and phenotype were unchanged, plasma viral control was maintained and no significant effect on HIV reservoirs was observed. Conclusions: These finding suggest that Poly-ICLC could be safely used for inducing transient innate immune responses in treated HIV+ subjects indicating promise as an adjuvant for HIV therapeutic vaccines. Trial Registration: www.ClinicalTrials.gov, identifier: NCT02071095.

Keywords: HIV-1; adjuvant; poly-ICLC; toll-like receptor ligand; vaccine.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • Carboxymethylcellulose Sodium / analogs & derivatives*
  • Carboxymethylcellulose Sodium / therapeutic use
  • Double-Blind Method
  • Female
  • HIV / immunology
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / metabolism
  • Humans
  • Immunity, Innate / drug effects*
  • Male
  • Middle Aged
  • Poly I-C / therapeutic use*
  • Polylysine / analogs & derivatives*
  • Polylysine / therapeutic use
  • Toll-Like Receptor 3 / metabolism*


  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Polylysine
  • poly ICLC
  • Carboxymethylcellulose Sodium
  • Poly I-C

Associated data

  • ClinicalTrials.gov/NCT02071095