SAFETY STUDY OF NONOXYNOL-9 AS A VAGINAL MICROBICIDE - EVIDENCE OF ADVERSE-EFFECTS

Nonoxynol-9 (N-9) is virucidal in vitro, and is therefore a candidate microbicide for preventing sexual transmission of HIV. However, the ac tivity of N-9 is nonspecific, suggesting that virucidal levels may pro duce adverse effects including epithelial disruption, inflammation of the genital mucosa, or both, A randomized placebo controlled trial of daily use of 100 mg of N-9 took place for 1 week in 40 female voluntee rs. Outcome measures included symptoms, colposcopic and histologic cha nges in the genital tract, and impact on vaginal flora. Genital irrita tion was reported by 10 of the N-9 and 5 of the placebo group. Colposc opy showed erythema in 9 of the N-9 group and 2 of the placebo group. Histologic inflammation was found in 7 of the N-9 group and 2 of the p lacebo group. Inflammatory changes were characterized by patchy infilt ration of the lamina propria predominantly with CD8(+) lymphocytes and macrophages, in the absence of epithelial disruption. A transient red uction in numbers of lactobacilli was observed in 9 of the 15 women us ing N-9, and 6 of 18 women using placebo. N-9 used for 7 days in a sta ndard spermicidal dose was associated with increased irritation, colpo scopic and histologic evidence of inflammation and was more frequently associated with reduction in numbers of lactobacilli during gel use. The clinical significance of the recruitment of cells susceptible to H IV infection to the genital mucosa is unknown but raises concerns abou t the suitability of N-9 as a microbicide when given in this dose.