Prevention and treatment of SHIVAD8 infection in rhesus macaques by a potent d-peptide HIV entry inhibitor

Proc Natl Acad Sci U S A. 2020 Sep 8;117(36):22436-22442. doi: 10.1073/pnas.2009700117. Epub 2020 Aug 20.

Abstract

Cholesterol-PIE12-trimer (CPT31) is a potent d-peptide HIV entry inhibitor that targets the highly conserved gp41 N-peptide pocket region. CPT31 exhibited strong inhibitory breadth against diverse panels of primary virus isolates. In a simian-HIV chimeric virus AD8 (SHIVAD8) macaque model, CPT31 prevented infection from a single high-dose rectal challenge. In chronically infected animals, CPT31 monotherapy rapidly reduced viral load by ∼2 logs before rebound occurred due to the emergence of drug resistance. In chronically infected animals with viremia initially controlled by combination antiretroviral therapy (cART), CPT31 monotherapy prevented viral rebound after discontinuation of cART. These data establish CPT31 as a promising candidate for HIV prevention and treatment.

Keywords: HIV entry inhibitor; HIV prevention; HIV treatment; NHP HIV model; d-peptide.

Publication types

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

MeSH terms

  • Animals
  • Anti-HIV Agents* / chemistry
  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • Drug Evaluation, Preclinical
  • Female
  • HIV Envelope Protein gp41 / antagonists & inhibitors
  • HIV Infections* / drug therapy
  • HIV Infections* / prevention & control
  • HIV Infections* / virology
  • HIV* / drug effects
  • HIV* / genetics
  • Macaca mulatta
  • Male
  • Simian Immunodeficiency Virus* / drug effects
  • Simian Immunodeficiency Virus* / genetics
  • Virus Internalization / drug effects*

Substances

  • Anti-HIV Agents
  • HIV Envelope Protein gp41