Safety and toxicity of Nonoxynol-9 gel as a rectal microbicide

Background and Objectives: Methods of HIV and STD prevention, which can be controlled by the receptive partner, are a high priority for research and d evelopment. Studies on the safety of Nonoxynol-9 (N-9) on the vaginal mucos a have yielded conflicting results. No Phase I study has evaluated the effe ct of N-9 an the rectal mucosa. Goals: To assess the safety of 52.5 mg of N-9 in a 1.5-g gel when applied o ne to four applicators per day to the rectum and penis. Study Design: The study included 25 HIV-negative and 10 HIV-positive, monog amous gay male couples in which each partner was exclusively insertive or r eceptive while using N-9 gel. Each participant served as his own control du ring placebo gel use compared to during N-9 gel use. Receptive partners und erwent anoscopic examination after 1 week of placebo use and after 2, 5, an d 6 weeks of N-9 gel use, with rectal biopsies obtained after I week of pla cebo use and after 5 and 6 weeks of N-9 gel use. Insertive partners had saf ety monitoring after 1. week of placebo use and after 2, 5, and 6 weeks of N-9. Results: No rectal ulcers were detected; superficial rectal erosions mere n oted in two HIV-negative participants. Abnormal or slightly abnormal histol ogic abnormalities of rectal biopsies mere detected in 31 (89%) receptive p articipants after N-9 gel use compared to 24 (69%) participants after 1 wee k of placebo gel use. Meatal ulceration, not caused by herpes simplex virus , was detected in one HIV-negative participant. Conclusion: Low-dose N-9 gel was not associated with macroscopic rectal and penile epithelial disruption or inflammation, but histologic abnormalities were commonly observed during N-9 gel as well as during placebo gel use.