Safety, pharmacokinetics and antiviral activity of PGT121, a broadly neutralizing monoclonal antibody against HIV-1: a randomized, placebo-controlled, phase 1 clinical trial

Nat Med. 2021 Oct;27(10):1718-1724. doi: 10.1038/s41591-021-01509-0. Epub 2021 Oct 7.


Human immunodeficiency virus (HIV)-1-specific broadly neutralizing monoclonal antibodies are currently under development to treat and prevent HIV-1 infection. We performed a single-center, randomized, double-blind, dose-escalation, placebo-controlled trial of a single administration of the HIV-1 V3-glycan-specific antibody PGT121 at 3, 10 and 30 mg kg-1 in HIV-uninfected adults and HIV-infected adults on antiretroviral therapy (ART), as well as a multicenter, open-label trial of one infusion of PGT121 at 30 mg kg-1 in viremic HIV-infected adults not on ART (no. NCT02960581). The primary endpoints were safety and tolerability, pharmacokinetics (PK) and antiviral activity in viremic HIV-infected adults not on ART. The secondary endpoints were changes in anti-PGT121 antibody titers and CD4+ T-cell count, and development of HIV-1 sequence variations associated with PGT121 resistance. Among 48 participants enrolled, no treatment-related serious adverse events, potential immune-mediated diseases or Grade 3 or higher adverse events were reported. The most common reactions among PGT121 recipients were intravenous/injection site tenderness, pain and headache. Absolute and relative CD4+ T-cell counts did not change following PGT121 infusion in HIV-infected participants. Neutralizing anti-drug antibodies were not elicited. PGT121 reduced plasma HIV RNA levels by a median of 1.77 log in viremic participants, with a viral load nadir at a median of 8.5 days. Two individuals with low baseline viral loads experienced ART-free viral suppression for ≥168 days following antibody infusion, and rebound viruses in these individuals demonstrated full or partial PGT121 sensitivity. The trial met the prespecified endpoints. These data suggest that further investigation of the potential of antibody-based therapeutic strategies for long-term suppression of HIV is warranted, including in individuals off ART and with low viral load.

Publication types

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

MeSH terms

  • Adult
  • Antiretroviral Therapy, Highly Active
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / immunology
  • Antiviral Agents / pharmacokinetics
  • Broadly Neutralizing Antibodies / administration & dosage*
  • Broadly Neutralizing Antibodies / immunology
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / virology
  • Double-Blind Method
  • Female
  • HIV Envelope Protein gp120 / antagonists & inhibitors
  • HIV Envelope Protein gp120 / immunology
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HIV Infections / pathology
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / pathogenicity
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / antagonists & inhibitors
  • Peptide Fragments / immunology
  • Placebos
  • Viral Load / drug effects
  • Viral Load / immunology
  • Young Adult


  • Antiviral Agents
  • Broadly Neutralizing Antibodies
  • HIV Envelope Protein gp120
  • HIV envelope protein gp120 (305-321)
  • Peptide Fragments
  • Placebos

Associated data