Global Campaign for Microbicides


UNAIDS & Advantage-S

At the 13th International AIDS Conference in Durban in July 2000, preliminary results of a randomised, controlled trial were announced that indicated that Advantage-S --an over-the-counter spermicide containing Nonoxynol-9 -- did not offer women protection against HIV transmission (Van Damme 2002). Indeed, the data suggest that when used several times a day, the product may increase a woman's risk of HIV infection, possibly by creating disruptions in the vaginal epithelium.

Advantage-S is a bio-adhesive gel marketed in the USA and China as a spermicidal contraceptive. It contains 52.5 mg of N-9 per dose, and is the lowest dose N-9 contraceptive on the market in the USA. The Phase 3 Advantage-S trial, sponsored by UNAIDS, was intended to evaluate its effectiveness as a microbicide, in the hope that it would prove effective against HIV.

This trial enrolled 991 sex workers in four developing countries --Thailand, South Africa, Ivory Coast and Benin. The women were offered free condoms and counselling as well as STI testing and treatment throughout the trial, and were randomized into one of two trial arms. One arm received Advantage-S and the other a placebo --a vaginal lubricant called Replens. Both groups were encouraged to use the product along with a condom at each act of intercourse. All participants were seen monthly at study clinics and followed over time.

The women reported having an average of 3.6 partners per day and about 70 coital acts per month during the study period. At the end of the trial, more genital lesions were observed among the participants using Advantage-S. The Advantage-S group was also found to have a significantly higher incidence of new HIV infections than the group using Replens.

It should be noted, however, that the incidence of new HIV infections in both study groups was lower than that seen in the wider population of sex workers from whom the women were recruited. This contradicts the fear expressed by some AIDS activists that participation in microbicide trials may in itself, increase women's HIV risk. The challenges associated with designing ethical prevention trials are complex, given the fact that some sero-conversion among participants is likely to occur despite condom promotion and other safeguards. But they are not insoluble.

There are at least three ways to interpret the Advantage-S results:

  1. The N-9 in the Advantage-S product caused an increased risk of male-to-female HIV transmission. The irritating effect that N-9 can have on the vaginal mucosa, and the greater risk of genital lesions in this group, support this interpretation.
  2. The Replens could have reduced transmission risk either by creating a mechanical barrier that prevented genital trauma during intercourse, or by favourably affecting vaginal flora to resist infection. The hyperviscosity and the lower pH of Replens both support this interpretation.
  3. Both interpretations could be correct at the same time.

The final analysis of these data still has not been published. Discussion of the presented data, however, has been vociferous as the scientific community debated how these study results should be interpreted.

In 2000 UNAIDS concluded that N-9 is not the answer for a user-controlled method of HIV prevention and called for more research to test other potential microbicides for safety and efficacy (Altman 2000). The CDC issued a letter in August 2000 saying that N-9 products "should not be recommended as an effective means of HIV prevention". They also advised using plain condoms instead of those coated with N-9; although they emphasized that using, "a condom lubricated with N-9 is clearly better than using no condom at all". There is far less N-9 on condoms (about 25 mg.) than in any of the over-the-counter birth control products.

In October 2001, the World Health Organization convened an expert group meeting to evaluate the data available on Nonoxynol-9 and establish consistent guidance for different users. Women's health advocates were included in the meeting to help assure that the messages proposed there realistically address women's needs, concerns and circumstances.

On June 28, 2002, WHO released the results of its long-awaited consensus document on the safety and effectiveness of Nonoxynol-9 for pregnancy and disease prevention.

The reports main findings are as follows:

  1. Despite earlier beliefs to the contrary, spermicides containing N-9 do not provide protection against HIV or bacterial STIs such as gonorrhea and chlamydia. When used frequently in the vagina, N-9 containing products may even increase risk of infection.
  2. Women who are at risk of HIV or have frequent intercourse should use a different form of contraception
  3. Spermicides containing N-9 remain a safe contraceptive option for women who use such products infrequently and who are not at risk of HIV.
  4. Under no circumstances, should N-9 containing products be used rectally.
  5. There are no data that demonstrate that condoms lubricated with Nonoxyol-9 are any more effective in preventing pregnancy or infection than condoms lubricated with silicone, therefore such condoms should no longer be promoted. (The report nonetheless notes that it is better to use a Nonoxynol-9 lubricated condom than no condom at all.)

To read the full WHO report, click here:
Read about the N-9 Call and Information

Van Damme L, Laga M et al, 2000. Vaginal microbicides: an update. Plenary presentation, 13th International AIDS Conference, Durban, South Africa. July, 12, 2000.
Altman, LK. 2000. Hopes for anti-HIV treatment dashed. New York Times, 13 July 13.