Preclinical Toxicological evaluation of the HIV entry inhibitor peptide 2P23 as a candidate rectovaginal microbicide

Pre-exposure prophylaxis of HIV infection with a microbicide is one of the most effective ways to block HIV/AIDS transmission. In this study, a potent and long-acting HIV entry inhibitor peptide 2P23 was developed as a novel HIV microbicide, and its toxicity and safety were evaluated through animal model in vivo for the first time, which provided a new effective means for the prevention of HIV/AIDS. In order to evaluate the potential effect to cause human toxicity and possible health hazards likely to arise from repeated rectovaginal application of 2P23, we conducted an acute toxicity in which a dose of 300 mg/kg of 2P23 was administrated by rectovaginal three times within 24-hour in male and female Sprague Dawley rats. Furthermore, a 90-day repeated rectovaginal treatment tests in rats were used to evaluate the chronic and reproductive toxicity of 50, 100, 200 mg/kg of 2P23. The effects of 2P23 administration on morbidity, mortality, clinical signs, changes in body weight, food consumption, clinical pathology, organ weight, hematological and physiological biochemical parameter indicators, histopathology, changes in rectovaginal microbiota, fertility, and early embryonic development were assessed. There were no mortality or abnormal clinical signs, no significant changes in body weight gain or hematological and physiological biochemical parameter indicators, no changes in necropsy and histopathology findings of vital organs, and no significant changes in rectum and vagina microbiota associated with the administration of 2P23. There were no effects on fertility and early embryonic development in male and female rats. The results indicate that 2P23 does not cause significant adverse effects in the 90-day and suggest that the no observed adverse effect level is 300 mg. This study has important application value and good innovation for the development of anti-HIV agents for rectovaginal administration. The novel HIV microbicide is safe and effective for the prevention and control of HIV/AIDS sexually transmitted infections, which enriches people's understanding of the novel HIV microbicide gel.