Effectiveness of COL-1492, a nonoxynol-9 vaginal gel, on HIV-1 transmission in female sex workers: a randomised controlled trial

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. Methods 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 dʹlvoire, 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. Findings 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. Interpretation 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.