Human Immunodeficiency Virus Type 1 Vpu Inhibitor, BIT225, in Combination with 3-Drug Antiretroviral Therapy: Inflammation and Immune Cell Modulation

Carolyn A. Luscombe*, Anchalee Avihingsanon, Khuanchai Supparatpinyo, Sivaporn Gatechompol, Win Min Han, Gary D. Ewart, Audrey S. Thomson, Michelle Miller, Stephen Becker, Robert L. Murphy

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

BIT225 is a first-in-class inhibitor of human immunodeficiency virus (HIV) type 1 Vpu. A phase II trial enrolled 36 HIV-1-infected, treatment-naive participants in Thailand to receive standard-of-care antiretroviral therapy (ART), tenofovir disoproxil fumarate/emtricitabine/efavirenz (Atripla), with 100 or 200 mg of BIT225 or placebo (daily) for 12 weeks. Combined treatment with BIT225 and ART was found to be generally safe and well tolerated, with antiviral efficacy comparable to that of ART alone. The secondary end point-soluble CD163, a marker of monocyte/macrophage inflammation-was noted to be significantly decreased in the BIT225 arm. Plasma-derived activated CD4+ and CD8+ T cells, natural killer cells, and interleukin 21 were increased in those treated with BIT225. These findings are consistent with inhibition of the known effects of HIV Vpu and may reflect clinically important modulation of inflammatory and immune function. Further clinical study is planned to both confirm and extend these important findings in treatment-naive, and treatment-experienced individuals. Clinical Trials Registration. Australian New Zealand Clinical Trials Registry (Universal Trial Number U1111-1191-2194).

Original languageEnglish (US)
Pages (from-to)1914-1922
Number of pages9
JournalJournal of Infectious Diseases
Volume223
Issue number11
DOIs
StatePublished - Jun 1 2021

Keywords

  • antiviral
  • BIT225
  • HIV-1
  • reduced inflammation
  • Vpu

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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