1. Prevention and treatment of SHIVAD8 infection in rhesus macaques by a potent d-peptide HIV entry inhibitor.
- Author
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Nishimura Y, Francis JN, Donau OK, Jesteadt E, Sadjadpour R, Smith AR, Seaman MS, Welch BD, Martin MA, and Kay MS
- Subjects
- Animals, Drug Evaluation, Preclinical, Female, HIV Envelope Protein gp41 antagonists & inhibitors, Macaca mulatta, Male, Anti-HIV Agents chemistry, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, HIV drug effects, HIV genetics, HIV Infections drug therapy, HIV Infections prevention & control, HIV Infections virology, Simian Immunodeficiency Virus drug effects, Simian Immunodeficiency Virus genetics, Virus Internalization drug effects
- 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., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)
- Published
- 2020
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