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

Amer Al-Khouja, Eugenie Shieh, Edward J. Fuchs, Mark A. Marzinke, Rahul P. Bakshi, Pamela Hummert, Anthony S. Ham, Karen W. Buckheit, Jennifer Breakey, Ethel D. Weld, Huan Chen, Brian S. Caffo, Robert W. Buckheit, Craig W. Hendrix

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)444-452
Number of pages9
JournalAIDS research and human retroviruses
Volume37
Issue number6
DOIs
StatePublished - Jun 2021

Keywords

  • HIV
  • clinical trials
  • pharmacokinetics
  • pharmacology
  • pre-exposure prophylaxis
  • rectal microbicide

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Infectious Diseases

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