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History of N-9 Testing

The history of evaluating N-9 products for possible use in HIV prevention is long and complicated. Even today, reasonable people can disagree on the meaning and proper interpretation of specific clinical trials. The scientific community has nonetheless come to the consensus that existing N-9 spermicides do not reduce HIV transmission and should not be promoted for HIV prevention.

Drawing conclusions about the effectiveness of N-9 for preventing HIV and STIs is complicated by the fact that existing birth control products differ dramatically by type (foams, films, sponges, and jellies) and by amount of active ingredient. Existing products have anywhere from 52 mg to 1000 mg. of N-9, as in the contraceptive sponge. Existing N-9 products are marketed only as contraceptives and make no claims as to effectiveness against STIs or HIV.

While studies in test tubes and animal models suggested that N-9 might be effective against HIV, clinical trials in humans produced mixed results. Several early observational studies indicated that N-9 might reduce the risk of HIV transmission, but the study designs were not sufficiently rigorous to permit definitive conclusions (Zeking et al, 1993). In an observational study of sex workers in Cameroon, for example, researchers found that those who used 100 mg N-9 suppositories regularly (in addition to or in place of condoms) had 70-80 percent fewer new HIV infections than the women who did not use the suppositories regularly. After adjusting for other risk factors, including concurrent condom use, consistent spermicide users had 90 percent fewer new HIV infections than less consistent users, and no more genital ulcers (Zekeng et al, 1993).

In the 1990s, researchers mounted four randomized controlled trials, each to evaluate a different N-9 product in a different setting. All failed to demonstrate a protective effect against HIV (Kreiss et al, 1992; Roddy 1998; Roddy 2000; Van Damme 2002). Indeed, the last study, a trial to evaluate Advantage-S sponsored by UNAIDS, raised the possibility that frequent use of N-9 might even increase risk of HIV transmission for some women by causing vaginal irritation (thus, making it easier for any HIV present in semen to enter the woman's blood stream).

It had long been known that under certain circumstances, N-9 could induce inflammatory changes and disruptions in the cells lining the vagina (the epithelium), which in theory could increase risk. Several studies looking specifically at irritation had demonstrated that disruption of the epithelium is related to how frequently the product is used and how strong it is. Lower dose products (52-150 mg) appear to cause little or no disruption when used once a day or less (Niruthisard 1992; Roddy 1993; Stevens et al. 1996).

Prior to the UNAIDS-funded trial, it had not been clear whether epithelial disruption would actually lead to increased risk of HIV. In the two earlier controlled trials in Cameroon, women who used an N-9 product had no greater risk of HIV than women in the control arm, even though they did have slightly higher rates of vulvar lesions. This led the author to conclude that while N-9 products did appear to increase epithelial lesions, the lesions did not translate into increased risk.

The Advantage-S trial sponsored by UNAIDS, suggested the opposite. These data indicated that when used several times a day, Advantage-S -- an existing over-the counter spermicide containing 52 mg. of Nonoxynol-9 (N-9) -- slightly increased a woman's risk of HIV infection (Van Damme, 2002).

On the basis of those findings, the CDC issued a letter 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. It concluded that:

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 Nonoxynol-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 nontheless notes that it is better to use a Nonoxynol-9 lubricated condom than no condom at all.)

Further Resources on N-9