Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption

N Engl J Med. 2019 Apr 18;380(16):1535-1545. doi: 10.1056/NEJMoa1802264.

Abstract

Background: Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption.

Methods: We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption. All the participants had undetectable plasma viremia (<20 copies of HIV RNA per milliliter) at the screening visit. After discontinuation of ART, participants received eight intravenous infusions of UB-421, at a dose of either 10 mg per kilogram of body weight every week (Cohort 1) or 25 mg per kilogram every 2 weeks (Cohort 2). The primary outcome was the time to viral rebound (≥400 copies per milliliter).

Results: A total of 29 participants were enrolled, 14 in Cohort 1 and 15 in Cohort 2. Administration of UB-421 maintained virologic suppression (<20 copies per milliliter) in all the participants (94.5% of measurements at study visits 2 through 9) during analytic treatment interruption, with intermittent viral blips (range, 21 to 142 copies per milliliter) observed in 8 participants (28%). No study participants had plasma viral rebound to more than 400 copies per milliliter. CD4+ T-cell counts remained stable throughout the duration of the study. Rash, mostly of grade 1, was a common and transient adverse event; one participant discontinued the study drug owing to a rash. A decrease in the population of CD4+ regulatory T cells was observed during UB-421 monotherapy.

Conclusions: UB-421 maintained virologic suppression (during the 8 to 16 weeks of study) in participants in the absence of ART. One participant discontinued therapy owing to a rash. (Funded by United Biomedical and others; ClinicalTrials.gov number, NCT02369146.).

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Retroviral Agents / therapeutic use*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes
  • Exanthema / chemically induced
  • HIV Infections / drug therapy*
  • HIV-1* / isolation & purification
  • Humans
  • Male
  • Middle Aged
  • T-Lymphocytes, Regulatory
  • Viral Load
  • Viremia / drug therapy

Substances

  • Anti-Retroviral Agents
  • Antibodies, Monoclonal, Humanized
  • UB-421

Associated data

  • ClinicalTrials.gov/NCT02369146