During the XIII International AIDS Conference held in Durban, South Africa, July 2000, researchers from the Joint United Nations Program on AIDS (UNAIDS) presented results of a study of a product, COL-1492,* which contains nonoxynol-9 (N-9) (1). N-9 products are licensed for use in the United States as spermicides and are effective in preventing pregnancy, particularly when used with a diaphragm. The study examined the use of COL-1492 as a potential candidate microbicide, or topical compound to prevent the transmission of HIV and STDs. The study found that N-9 did not protect against HIV infection and may have caused more transmission. The women who used N-9 gel became infected with HIV at approx. a 50% higher rate than women who used the placebo gel.
CDC has released a “Dear Colleague” letter that summarizes the findings and implications of the UNAIDS study at http://www.cdc.gov/hiv; a hard copy is available from the National Prevention Information Network, telephone (800) 458-5231. Future consultations will be held to re-evaluate guidelines for HIV, STDs, and pregnancy prevention in populations at high risk for HIV infection.
FDA ANSWERS QUESTIONS REGARDING PRODUCTS CONTAINING NONOXYNOL-9 (N-9)
The Food and Drug Administration answered questions on Monday, June 21, 2004 that were asked earlier in the year by the U.S. House Subcommittee on Criminal Justice, Drug Policy and Human Resources. In their response, the FDA stated that studies show that Nonoxynol-9 (N-9) does NOT protect against HIV/AIDS and other STDs, but is unsure if it actually increases the risk of contracting HIV/AIDS.
While the FDA will allow vaginal contraceptive devices containing N-9 to stay on the market, they will require a new label which informs users that N-9 does not protect against HIV/AIDS and other STDs, and that it is possible that it may increase the risk of getting HIV/AIDS. The FDA is currently reviewing whether condoms containing N-9 should be labeled differently, but does not believe that condoms containing N-9 should be removed from the market.
The official statements of the Food and Drug Administration are listed below:
Department of Health and Human Services
Food and Drug Administration (FDA)
“Microbicides” have been suggested as potential protection against HPV and other STDs. (a) What microbicides currently are available? (b) Please explain the effectiveness or lack of effectiveness of existing microbicides in protecting against HPV, HIV/AIDS and other STDs?(c)
The spermicide Nonoxynol-9 (N-9) has been promoted for the prevention of pregnancy and STDs. For nearly 15 years, a growing number of studies have actually demonstrated an increased risk for HIV infection associated with N-9 use.
Now researchers report in the March 2004 issue of the medical journal Obstetrics and Gynecology that the chances of becoming pregnant over a six-month period may be as high as 22 percent for women who rely on N-9 for contraception.
The Subcommittee wrote to the FDA on April 9, 2003 and stated “N-9 was originally intended for use as a spermicide for contraception, yet in this regard, there are no data to indicate that condoms with N-9 are any more effective than condoms that do not contain N-9. The availability of condoms laced with N-9, therefore, provide no benefit over what is otherwise available for contraception but do cause increased risks for HIV infection. This danger with no known beneficial offset calls into question the overall safety and effectiveness of such products and thereby the FDA approval for production and sale.”
With the growing evidence that N-9 use is not effective and may be dangerous, will the FDA consider pulling N-9 products from commercial availability until its safety and effectiveness can be proven?
Response: There are no prescription or OTC microbicides approved for prevention of HPV, HIV/AIDs or other STDs.
The spermicide N-9 is a non-ionic surfactant that works as a vaginal contraceptive by damaging the cell membrane of sperm. It has been shown in certain in vitro studies to damage the cell wall of certain STD pathogens and to have activity against certain bacterial and viral STD pathogens, including HIV.
Because N-9 kills the AIDS virus (HIV) and other STD pathogens in vitro, it has been suggested, over the years, that the drug might help prevent or reduce the risk of transmission of the AIDS virus and other STDs in humans. However, labeling for N-9 vaginal contraceptive products and lubricants containing N-9 has never stated or suggested this.
Although information available to the general public may create the misperception that N-9 might help decrease the risk of becoming infected with the AIDS virus and other STDs, more recently, a number of studies have demonstrated that N-9 does not protect against the AIDS virus (HIV) or other STDs.
However, only a few recent studies have suggested that there may be a greater risk of HIV infection associated with frequent N-9 use. These studies used a very high-risk population of commercial sex workers as subjects. FDA is working to address this risk information in light of the intended use of N-9 products as contraceptives.
As you note, the March 2004 medical journal Obstetrics and Gynecology published spermicide efficacy studies involving N-9 vaginal spermicides, which showed that the probability of pregnancy during typical use for spermicides containing N-9 was between 10-22 (this means that per year, 10-22 women out of 100 will become pregnant). N-9 spermicides may be just as effective as other non-hormonal birth control methods; 14-15 women will become pregnant using the male latex condom, 20-32 women will become pregnant using the diaphragm or cervical cap, 19-27 women will become pregnant using [rhythm — quite different than Natural Family Planning which gets results equivalent to chemical birth control methods], etc.
The typical use pregnancy rates were obtained from the literature – R.A. Hatcher, J. Trussell, F. Stewart et al., Contraceptive Technology, 17th revised edition (1998) and 18th edition (in press), and data adapted from clinical trial product information submitted to FDA and NIH.
The N-9 efficacy studies described above are for stand-alone vaginal contraceptives containing N-9, such as films, suppositories, foams and gels. These studies show that N-9 is effective in preventing pregnancy when used correctly.
FDA has decided to allow these products to remain on the marketplace, but will require manufacturers to label their products with warnings that advise consumers that N-9-containing OTC vaginal contraceptive drug products do not protect against the AIDS virus and other STDs and that frequent use by women at risk for HIV may increase their risk of getting HIV from infected partners.
FDA published a proposed rule requiring these warnings for OTC vaginal contraceptives on January 16, 2003, 68 FR 2254. FDA has also published a call for data notice on December 13, 2003 (68 FR 75585) for vaginal lubricants and moisturizers, some of which contain N-9. These are drugs that were not previously reviewed by FDA when the OTC drug review process began. The review will determine if these ingredients are generally recognized as safe and effective for their labeled uses.
Condoms containing N-9 are not under the purview of FDA’s proposed rule of 1/16/03. Condoms are medical devices. N-9, a drug, is added to the lubricant system of some condoms in order to provide a spermicidal effect in the event of condom breakage or slippage where there might be semen spillage in the vagina. In 1981, data supporting the addition of N-9 to the condom lubricant system included results from post-coital testing showing a great reduction in sperm motility. FDA believed that confirmatory contraceptive studies – which would need to be unusually large
an expected small added effect – were unnecessarily burdensome.
FDA believes that a significant portion of the market for condoms with N-9 consists of heterosexual couples at low HIV risk who use this product for contraceptive protection. We believe that this is a reasonably safe use of a condom with N-9, and the data do not support removal of this product from the market for these low risk populations.
The studies that suggested an increased risk of HIV transmission associated with frequent use of N-9 tested the use of stand-alone spermicides by women, not the use of condoms with N-9 in the lubricant. Given that condoms themselves are an effective barrier to transmission of HIV [this is not confirmed by recent research], and that N-9 does not compromise these barrier properties, it is not clear how those study findings relate to condoms with N-9. However, the Agency is currently reviewing labeling of condoms with N-9 to make sure that information regarding appropriate use of this product is properly presented to the consumer in light of new information about the potential risks of N-9. [Jessemyn Pekari, National Abstinence Clearinghouse, 30Jun04]
MORE EVIDENCE PROVES NONOXYNOL-9 INCREASES THE RISK OF HIV/AIDS AND OTHER STDS
Evidence continues to mount which proves that the lubricant Nonoxynol-9 (N9) found on many brands of condoms actually increases the risk of contracting HIV/AIDS and other sexually transmitted diseases. Some reports have stated the risk as much as doubles for women and homosexual men.
Citizens in London were upset to learn that its Department of Health has known about the risks associated with N9, but did not intend to warn the public.
“Either civil servants knew about this and covered it up, in which case it is a scandal with potentially devastating effects on the health of young people, said British citizen Eileen McCloy, or they didn’t know about it, in which case they’re not up to the job of protecting our health.”
[AIDS Weekly & Law, 10/21/04, Sunday Times (London), 09/05/04;
Jessemyn Pekari, Abstinence Clearinghouse Update, 11/10/04]