HIV entry inhibitor peptide 2P23 demonstrates no significant toxicity in 90-day rectovaginal rat study.

Pre-exposure prophylaxis (PrEP) with microbicides is a critical strategy to prevent HIV/AIDS transmission, especially in populations where oral PrEP adherence or access is challenging. Current prevention methods often face issues with long-term compliance or systemic side effects. Developing a potent, long-acting, and locally applied HIV entry inhibitor peptide offers a promising alternative, addressing the need for safe and effective topical prevention agents.

Researchers evaluated the toxicity and safety of the HIV entry inhibitor peptide 2P23 in male and female Sprague Dawley rats. An acute toxicity study involved rectovaginal administration of 300 mg/kg 2P23 three times within 24 hours. Subsequently, a 90-day repeated rectovaginal treatment test assessed chronic and reproductive toxicity using doses of 50, 100, and 200 mg/kg 2P23. Primary endpoints included morbidity, mortality, clinical signs, body weight, food consumption, clinical pathology, organ weight, hematological and physiological biochemical parameters, histopathology of vital organs, changes in rectovaginal microbiota, fertility, and early embryonic development.

The study reported no mortality or abnormal clinical signs across any dose group in both acute and 90-day studies. There were no significant changes in body weight gain or food consumption. Hematological and physiological biochemical parameter indicators remained normal, showing no adverse effects related to 2P23 administration. Necropsy and histopathology findings of vital organs revealed no significant changes, and the rectovaginal microbiota was unaffected. Importantly, 2P23 had no effects on fertility or early embryonic development in either male or female rats. The results indicate that 2P23 does not cause significant adverse effects over 90 days, with the no observed adverse effect level (NOAEL) determined to be 300 mg.