An international trial of the spermicide nonoxynol-9 has concluded that it is ineffective in protecting women from HIV transmission. Microbicides are chemical substances - in the form of a gel, cream, suppository or film - which kill viruses and bacteria when applied vaginally or rectally before sexual intercourse. Over 50 potential microbicides are currently undergoing evaluation, some are in human trials but it is unlikely one will be available in the next five years.
The trial began in 1996 and recruited 700 female sex workers in Benin, Cote d’Ivoire, South Africa and Thailand. Preliminary data, which were released in March, suggested that the spermicide formulation, Advantage S made by Columbia Laboratories would prove effective in reducing HIV infection rates.
Since an effective vaccine still appears many years from development, a microbicide represents the next best hope for the millions of women, under threat of infection, especially in the developing world.
The Phase III study was double blinded, so neither the researchers nor the participants knew whether they were receiving Advantage S or placebo - the vaginal lubricant Replens. The women were asked to keep a diary of their activities. Since there was a placebo arm to the trial, the women were provided with condoms, which they were advised to urge their partners to use.
The researchers had anticipated that those receiving the placebo would have higher rates of infection than those who received Advantage S. Several safety studies carried out before the start of the phase III trial failed to show any side-effects usually associated with nonoxynol-9 such as genital sores and irritation.
Much to the dismay of everyone involved, the spermicide actually afforded the women less protection than the placebo.
Many of the women admitted to backdating the diary when they went to the hospital for further supplies of the product. This has raised concerns about the reliability of the women as test subjects.
The results of the trial have raised ethical questions that may affect the future study of all microbicides; in particular, critics have questioned the ethics of using a placebo against a potentially life-threatening virus. Other concerns were raised over the way that the use of condoms may have coloured the results by providing an extra level of protection to the women who decided to use them. Controversially, some researchers have argued that the use of condoms, ethical as it may be, limits the usefulness of data.
Currently, Columbia Laboratories is being sued by its shareholders who are claiming that the company misled them and that over one million dollars of stock was sold off at inflated prices before the company announced details of the product’s failure.
Detailed final analysis of the trial will be presented at the International AIDS Conference in Durban, South Africa on July 12 2000.