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

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.

• Authors: Yoshiaki Nishimura, J Nicholas Francis, Olivia K Donau, Eric Jesteadt, Reza Sadjadpour, Amanda R Smith, Michael S Seaman, Brett D Welch, Malcolm A Martin, Michael S Kay
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 117 Issue 36 Pg. 22436-22442 (09 08 2020) ISSN: 1091-6490 [Electronic] United States
• PMID: 32820072 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 the Author(s). Published by PNAS.

Chemical References

• Anti-HIV Agents
• HIV Envelope Protein gp41

Topics

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