Nonoxynol-9 (rINN, nonoxinol-9) is an over-the-counter spermicide that has in-vitro anti-HIV-1 activity. Results of studies of its effectiveness in prevention of HIV-1 infection in women have been inconclusive. We aimed to assess effectiveness of this vaginal gel.

We did a randomised, placebo-controlled, triple-blinded, phase 2/3 trial with COL-1492, a nonoxynol-9 vaginal gel, in 892 female sex workers in four countries: Benin, Côte d'lvoire, South Africa, and Thailand. 449 women were randomly allocated nonoxynol-9 and 443 placebo. Primary endpoint was incident HIV-1 infection. Secondary endpoints included Neisseria gonorrhoeas and Chlamydia trachomatis infections. Analysis was by intention to treat.

765 women were included in the primary analysis. HIV-1 frequency in nonoxynol-9 users was 59 (16%) of 376 compared with 104 (27%) of 389 in placebo users (402·5 vs 435·0 woman-years; hazard ratio adjusted for centre 1·5; 95% Cl 1·0–2·2; p=0·047). 239 (32%) women reported use of a mean of more than 3·5 applicators per working day, and in these women, risk of HIV-1 infection in nonoxynol-9 users was almost twice that in placebo users (hazard ratio 1·8; 95% Cl 1·0–3·2). 516 (68%) women used the gel less frequently than 3·5 times a day, and in these, risk did not differ between the two treatments. No significant effect of nonoxynol-9 on N gonorrhoeas (1·2; 0·9–1·6) or C trachomatis (1·2; 0·8–1·6) infections was reported.

This study did not show a protective effect of COL-1492 on HIV-1 transmission in high-risk women. Multiple use of nonoxynol-9 could cause toxic effects enhancing HIV-1 infection. This drug can no longer be deemed a potential HIV-1-prevention method. Assessment of other microbicides should continue.