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Updated: Apr 27, 2026
Ex Vivo Infection of Human Lymphoid Tissue and Female Genital Mucosa with Human Immunodeficiency Virus 1 and Histoculture
Published on: October 12, 2018
Development of HIV-1 rectal-specific microbicides and colonic tissue evaluation
Charlene S Dezzutti1, Julie Russo2, Lin Wang2
1Magee-Womens Research Institute, Pittsburgh, Pennsylvania, United States of America; Department Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Novel rectal microbicide (RM) formulations effectively delivered antiretroviral drugs to rectal tissue, demonstrating safety and efficacy in preclinical models. Flexible sigmoidoscopy tissues showed comparable results to surgical tissues for RM evaluation.
Area of Science:
- Pharmacology
- Virology
- Gastroenterology
Background:
- Topical microbicide development has expanded to rectal microbicides (RMs) due to anatomical and functional differences between the gastrointestinal tract and vagina.
- The need for safe and effective antiretroviral drug delivery to rectal mucosal tissue necessitates unique RM formulations.
Purpose of the Study:
- To develop and characterize novel rectal microbicide (RM) formulations for the delivery of antiretroviral drugs (Tenofovir and UC781).
- To evaluate the efficacy and safety of these RM formulations using ex vivo human colonic tissue.
Main Methods:
- Formulation of Tenofovir (TFV) and UC781 into liquid and gel rectal microbicides (RMs).
- Characterization of RM formulations for pH, viscosity, osmolality, and drug content.
- Ex vivo testing on colonic tissues from surgical resections and flexible sigmoidoscopy (flex sig) to assess HIV-1 replication, tissue viability (MTT assay), and histology.
Main Results:
- All RM formulations exhibited neutral pH and were isoosmolar.
- Both TFV and UC781 RM formulations successfully protected colonic tissue from HIV-1 replication, maintaining tissue viability and architecture.
- Flexible sigmoidoscopy tissues demonstrated comparable, and in some cases more pronounced, HIV-1 replication trends than surgically resected tissues.
Conclusions:
- Unique rectal microbicide (RM) formulations for Tenofovir and UC781 were successfully developed and demonstrated safety and efficacy in preclinical ex vivo models.
- Flexible sigmoidoscopy-derived tissues are a viable and comparable alternative to surgical tissues for evaluating rectal microbicide (RM) efficacy and safety.
