Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 117, Issue 36, Pages 22436-22442Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.2009700117
Keywords
HIV entry inhibitor; D-peptide; NHP HIV model; HIV prevention; HIV treatment
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Funding
- Intramural Research Program of the National Institute of Allergy and Infectious Diseases
- NIH [AI076168, AI150464, AI95172]
- Bill and Melinda Gates Foundation CAVD Grant [OPP1146996]
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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 similar to 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.
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