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Examining the Safety, Pharmacokinetics, and Pharmacodynamics of a Rectally Administered IQP-0528 Gel for HIV Pre-Exposure Prophylaxis: A First-In-Human Study.

Authors
  • Al-Khouja, Amer1
  • Shieh, Eugenie1
  • Fuchs, Edward J1
  • Marzinke, Mark A1, 2
  • Bakshi, Rahul P1
  • Hummert, Pamela1
  • Ham, Anthony S3
  • Buckheit, Karen W3
  • Breakey, Jennifer1
  • Weld, Ethel D1
  • Chen, Huan4
  • Caffo, Brian S4
  • Buckheit, Robert W3
  • Hendrix, Craig W1
  • 1 Division of Clinical Pharmacology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • 2 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
  • 3 ImQuest BioSciences, Frederick, Maryland, USA.
  • 4 Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA.
Type
Published Article
Journal
AIDS Research and Human Retroviruses
Publisher
Mary Ann Liebert
Publication Date
Jun 01, 2021
Volume
37
Issue
6
Pages
444–452
Identifiers
DOI: 10.1089/AID.2020.0188
PMID: 33371779
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

A lubricating microbicide gel designed for rectal and vaginal use would provide a behaviorally congruent strategy to enhance pre-exposure prophylaxis adherence and reduce HIV infection risk. In this study, we report the first-in-human evaluation of such a gel containing 1% IQP-0528, an investigational antiretroviral. Seven HIV-1-negative participants received one 10 mL rectal dose of radiolabeled 1% IQP-0528 gel. We assessed safety; IQP-0528 pharmacokinetics in plasma, and rectal and vaginal tissue; ex vivo local pharmacodynamics (PD); and colorectal distribution. The 1% gel was determined to be safe with one mild event attributed to study product and no effects on rectal tissue histology. All concentrations measured in plasma and vaginal tissue were below the limit of quantitation. Median IQP-0528 concentrations in rectal tissue exceeded the in vitro EC95 against HIV-1 (0.07 ng/mg) by 3-5 h of dosing and remained above this concentration for at least 24 h, despite a 3-log reduction in concentration over this duration of time. Rectal tissue PD-assessed by ex vivo HIV challenge-demonstrated significant p24 antigen reduction 3-5 h postdose compared with baseline (p = .05), but not 24-26 h postdose (p = .75). Single-photon emission computed tomography/computed tomography imaging revealed that product distribution was localized to the rectosigmoid. The IQP-0528 gel possesses desirable features for a topical microbicide including: local safety with no systemic absorption, delivery of locally high IQP-0528 concentrations, and significant reductions in ex vivo HIV infectivity. However, the gel is limited by its rapid clearance and inability to penetrate vaginal tissues following rectal dosing. Clinical Trial Registration number: NCT03082690.

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