*11.2.3.1. Nonoxinol 9 (N-9)*

This prototype detergent compound is the non-ionic surfactant nonoxynol 9 (N-9) that forms a chemical barrier between the vaginal mucosa and the ejaculate. The nonoxynol 9 is a spermicide low cost and easy access sulfactant that proved effective against HIV-1 infection, *in vitro* tests [262]. However, since nonoxynol 9 disrupts the phospholipid membrane of cells, it can cause non-specific damage to vaginal epithelium cells, uterine and cervical tissue thus increasing rather than decreasing the likelihood of HIV-1 infection [260, 261]. In a blinded, randomized controlled efficacy trials of nonoxynol 9, in seronegative sex workers for HIV-1 in Cameroon, the data showed no difference in the rate of HIV-1 infection, though a higher incidence of genital ulcers with the use of nonoxynol 9 compared with placebo was observed [263]. In turn, the efficacy trial in female sex workers in four countries showed an association between N-9 and increased HIV-1 seroincidence when nonoxynol 9 has been used more than three times daily [264]. These findings suggest that the toxicity of nonoxynol 9 on tissue of the vaginal mucosa at higher doses would be a possible cause for increased transmission among frequent users, which led researchers to disregard the use of nonoxynol 9 as a HIV-1 preventive microbicide [191].

#### *11.2.3.2. C31G*

C31G (Savvy®), or cetyl betaine and myristamine oxide, is a surfactant with the potential to microbicide and contraceptively spermicide, in addition it has *in vitro* activity against C. trachomatis, HSV, and HIV-1 [265-267]. A clinical study has shown that many patients are reluctant to use it because of associated burning sensations [268]. The C31G co-polymer gel (1%, 0.5% and 1.7%) was evaluated, but the results were inconclusive regarding their safety and efficacy for preventing HIV-1 infection, and clinical trials of C31G have recently been discontinued [268, 269].
