title: Safety and toxicity of nonoxynol-9 gel as a rectal microbicide.
abstract: OBJECTIVE
  Methods of HIV and STD prevention, which can be controlled by the receptive partner, are a high priority for research and development. Studies on the safety of Nonoxynol-9 (N-9) on the vaginal mucosa have yielded conflicting results. No Phase I study has evaluated the effect of N-9 on the rectal mucosa.
  
  
  OBJECTIVE
  To assess the safety of 52.5 mg of N-9 in a 1.5-g gel when applied one to four applicators per day to the rectum and penis.
  
  
  METHODS
  The study included 25 HIV-negative and 10 HIV-positive, monogamous gay male couples in which each partner was exclusively insertive or receptive while using N-9 gel. Each participant served as his own control during placebo gel use compared to during N-9 gel use. Receptive partners underwent anoscopic examination after 1 week of placebo use and after 2, 5, and 6 weeks of N-9 gel use, with rectal biopsies obtained after 1 week of placebo use and after 5 and 6 weeks of N-9 gel use. Insertive partners had safety 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 were noted in two HIV-negative participants. Abnormal or slightly abnormal histologic abnormalities of rectal biopsies were detected in 31 (89%) receptive participants after N-9 gel use compared to 24 (69%) participants after 1 week of placebo gel use. Meatal ulceration, not caused by herpes simplex virus, was detected in one HIV-negative participant.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Washington, Seattle, USA.
authors.forename: S R
authors.initials: SR
authors.lastname: Tabet
authors.forename: C
authors.initials: C
authors.lastname: Surawicz
authors.forename: S
authors.initials: S
authors.lastname: Horton
authors.forename: M
authors.initials: M
authors.lastname: Paradise
authors.forename: A S
authors.initials: AS
authors.lastname: Coletti
authors.forename: M
authors.initials: M
authors.lastname: Gross
authors.forename: T R
authors.initials: TR
authors.lastname: Fleming
authors.forename: S
authors.initials: S
authors.lastname: Buchbinder
authors.forename: R C
authors.initials: RC
authors.lastname: Haggitt
authors.forename: H
authors.initials: H
authors.lastname: Levine
authors.forename: C W
authors.initials: CW
authors.lastname: Kelly
authors.forename: C L
authors.initials: CL
authors.lastname: Celum
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects; D015658:HIV Infections / Q000517:prevention & control*; D018451:Homosexuality, Male; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D017137:Nonoxynol / Q000009:adverse effects / Q000494:pharmacology*; D010413:Penis / Q000166:cytology / Q000187:drug effects*; D012007:Rectum / Q000187:drug effects*; D012749:Sexually Transmitted Diseases / Q000517:prevention & control*
chemical_list: D000890:Anti-Infective Agents; D017137:Nonoxynol