Nonoxynol-9 and the Risk of HIV Transmission

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The purpose of this Epi Update is to summarize recent data on the effectiveness of nonoxynol-9 as a microbicide, with particular reference to its effect on HIV transmission. While the effectiveness of nonoxynol-9 as a spermicide is well known, its usefulness as a microbicide has been questionned, and in fact recent data indicate that nonoxynol-9 may actually increase the risk of HIV transmission. This Epi Update examines the implications of these data in the context of HIV prevention efforts.


Microbicides are chemical substances that kill viruses and bacteria, and thus, have the potential to reduce the transmission of HIV and other sexually transmitted pathogens when applied vaginally or rectally before sexual intercourse. The development of an effective microbicide is an important research objective since it would not only improve the effectiveness of condoms in preventing disease transmission, but more importantly it would offer an alternative for women to protect themselves from infection without having to obtain the cooperation of their male sexual partner (to wear a male condom). Such an alternative would be especially welcome since the vast majority of global HIV transmissions occur via heterosexual activity.

An 'ideal' microbicidal product would be effective against multiple STDs, including HIV, safe to use several times daily, fast acting, acceptable to users, affordable, colorless, odorless, easy to store and to use, easy to obtain, and available in a variety of preparations, including with or without a contraceptive component. None of the compounds currently in development meet these ideal standards and experts say it is unlikely that any one product will meet them all. The immediate priority is to develop a microbicidal product that would provide protection against HIV. (1)

Nonoxynol-9 (N-9) is one of the best studied microbicides for the prevention of HIV and other sexually transmitted infections. N-9 was initially developed as a spermicide, a chemical that kills sperm and therefore prevents pregnancy. These chemicals are used in contraceptive spermicide products and as complementary components in the lubricant of barrier methods of contraception, such as the male condom. Studies have demonstrated that when spermicides are used alone, they are 75-85% effective in preventing pregnancy. (2,3) In addition, N-9 has also been identified as a compound that can kill viruses and bacteria, and so has been proposed as a candidate microbicide for HIV prevention. Laboratory studies have shown that N-9 kills or stops the growth of the HIV virus as well as the pathogens of other sexually transmitted infections such as genital herpes, gonorrhea, syphilis, trichomoniasis and chlamydia. (4)

A number of products containing N-9 are licenced for use as spermicides in both the United States and Canada. These products are available without a prescription and come in a variety of forms, including creams, films, foams, gels, suppositories, and as a lubricant on spermicidal condoms. In Canada, N-9 is found as a component of the following contraceptive products: Advantage 24 contraceptive gel, Delfen foam, vaginal contraceptive film (VCF), KY Plus Jelly spermicidal lubricant, Protectaid contraceptive sponge, and Emko, Encare, Ramses and Durex brands of condoms with spermicide. However, in Canada at present, there are no products with N-9 that are licensed or indicated for use as microbicides. (5)

Evidence Regarding Nonoxynol-9 and HIV Transmission

The frequent use of nonoxynol-9 can induce lesions and ulcerations to genital mucosa, thereby increasing the probability of transmitting infectious agents. 6 Studies have also indicated that these adverse effects of N-9 are dose related, supporting the notion that a potentially narrow margin of safety may exist for N-9. (7)

While laboratory studies clearly indicated that N-9 could be an effective barrier to HIV, clinical trials in humans have produced mixed results. Several observational studies have indicated that N-9 may reduce the risk of HIV transmission, but the study design did not permit definitive conclusions. (8-10) A meta-analysis investigation that combined data from several studies concluded that N-9 may have a protective effect against both gonorrhea and chlamydia11, but a recent randomized controlled trial found that N-9 gel did not protect against urogenital gonococcal or chlamydial infection. (12) As well, a recent report from WHO concluded that spermicides containing nonoxynol-9 do not protect against gonorrhoea and chlamydia. (13) A recently-published cohort study found no evidence of N-9 protection against HIV, (14) similar to the results of two controlled trials on this subject. One trial found no significant protection but a higher incidence of genital ulcers in the N-9 group compared to the control group, (15) and another trial found increased HIV infections in the N-9 group compared to the control group though this difference was not statistically significant. (16)

The most significant recent data are from a study conducted between 1996 and 2000 among sex trade workers in four countries: Benin, Cote D'Ivoire, South Africa and Thailand with COL-1492, a vaginal gel containing Nonoxynol-9. The results showed that this gel had an adverse effect on vaginal integrity when used frequently, thus increasing women's susceptibility to HIV-1 infection. At low frequency use, nonoxynol-9 had no effect , either positive or negative, on HIV-1 infection. (17)

The association between N-9 and genital lesions was also seen in a study of monogamous, low risk women who had a much lower frequency of sexual intercourse than the sex workers in the UNAIDS study. In this second study, women applied a vaginal N-9 gel or a placebo gel twice daily, and the N-9 group had significantly more vaginal itching, burning and mucosal lesions.18 While it is difficult to extrapolate the findings of these two studies to the general population in terms of sexual frequency and dosage and mode of N-9 use (including the occasional use of an N-9 lubricated condom), the theoretical benefits of N-9 use in such situations would have to be weighed against the demonstrated potential for harmful side effects.


Taken together, the recent evidence is convincing that frequent use of N-9 does not reduce the risk of infection by HIV, and may in fact increase the risk by causing disruptions and lesions in the genital mucosal lining. There are currently few data available to address the question of whether these results also apply to situations in which the dosage and/or frequency of N-9 use is lower. WHO has stated that Nonoxynol-9 clearly does not prevent HIV infection and may even favour infection if used frequently. (13)

It is worth noting that the United States Food and Drug Administration has proposed new warning labels for over-the counter contraceptive drugs that contain this spermicide. (19) The warning will state that these contraceptives do not protect against infection from HIV or other STDs. The proposed label warnings would also tell consumers that the use of these contraceptives can increase vaginal irritation, which may raise the risk of contracting HIV and other STDs.

Health Canada has never recommended N-9 on its own as an effective means of HIV prevention. Current assessment of the data indicates that:

§ N-9 should not be promoted as an effective means of HIV prevention. In particular, individuals who cannot use a condom for HIV prevention should not be counseled to use N-9 as an alternative.

§ The best STD and HIV barrier is a latex condom without N-9. However, a condom lubricated with N-9 is probably better than no condom at all. The protection provided by the condom would appear to outweigh the potential risk of the N-9, at least of low frequency of use and dosage.

§ If N-9 is used as an aid to contraception, its benefit should be carefully considered in light of the increased risk of genital lesions and the resulting potential for an increased risk of HIV transmission. Similar recommendations have been released from the Centers for Disease Control and Prevention in the USA. (20,21)

Future Directions

These disappointing data on the ineffectiveness of N-9 as a microbicide serve to further reinforce the importance and urgency of research on the development of other possible compounds as microbicides. Other classes of compounds that show promise include topical non-nucleoside reverse transcriptase inhibitors (such as efavirenz), inhibitors of viral attachment (such as cellulose sulphate), and natural products (such as buffer gels). In 2002, there has been a new development of an experimental gel which appears to be a safe, effective contraceptive, according to animal studies. The compound known as mandelic acid condensation polymer or SAMMA, blocked HIV and two strains of herpes simplex virus in laboratory testing. Researchers believe the results are encouraging and justify further testing. (22)

There is an urgent need to develop a microbicide which can substantially reduce the transmission of sexually transmitted infections, including HIV, and which can be used by women. For individuals who are unable to access condoms or negotiate condom use, particularly women, the identification of safe and effective alternatives in HIV prevention is a public health priority.


  1. Microbicides. Update: Issue Update. The Henry J. Kaiser Family Foundation. May 2001.
  2. Trussell J, Hatcher RA, Cates W Jr et al. Contraceptive failure in the United States: an update. Stud Fam Plann 1990;21(1):51-4.
  3. Steiner MJ, Hertz-Picciotto I, Schulz KF et al. Measuring true contraceptive efficacy. A randomized approach-condom vs. spermicide vs. no method. Contraception 1998;58(6):375-8.
  4. U.S. National Library of Medicine. Spermicides (Vaginal). MEDLINE plus Health Information. Micromedex Inc. Revised July 28, 1993.
  5. Mueller T (Personal communication, September 8, 2000). Therapeutic Products Programme, Health Canada.
  6. Gagne, Nathalie; Cormier, Helene; Omar, Rabeea F; Desormeaux, Andre; Gourde, Pierret. Protective Effect of a thermoreversible gel against the toxicity of nonoxynol-9 Sexually Transmitted Diseases, 1999, Vol. 26. N.3 177-183
  7. Rustomjee R, Abdool Karim Q, Abdool Karim SS et al. Phase I trial of nonoxynol-9 film among sex workers in South Africa. AIDS 1999;13(12):1511-5.
  8. Wittkowski KM, Dietz K. The protective effect of condoms and Nonoxynol-9 against HIV infection. National Conference Women and HIV, May 4-7, 1997 (Abstract no. P1.68).
  9. Wittkowski KM, Susser E, Dietz K. nonoxynol-9 in preventing heterosexual transmission of HIV- using multivariate methods in re-analysing previous and planning future studies. 12th International AIDS Conference, June 28-July 3, 1998, Geneva, Switzerland (Abstract no. 33142).
  10. Wittkowski KM, Susser E, Dietz K. The protective effect of condoms and Nonoxynol-9 against HIV infection. Am J Pub Health 1998;88(4):590-6 and Comment in: Am J Public Health 1999;89(1):198-10.
  11. Cook RL, Rosenberg MJ. Do spermicides containing N-9 prevent sexually transmitted infections? A meta-analysis. Sex Transm Dis 1998;25(3):144-150.
  12. Roddy R E, Zekeng L, Ryan KA, Tamoufe U, Tweedy KG. Effect of nonoxynol-9 gel on urogenital gonorrhea and chlamydial infection: a randomized controlled trial. JAMA 2002; 287: 1117-1122
  13. "Nonoxynol-9 Ineffective in Preventing HIV infection".28 June 2002. Press Release WHO/55.
  14. Hira SK, Feldblum PJ, Kamanga J et al. Condom and Nonoxynol-9 use and the incidence of HIV infection in serodiscordant couples in Zambia. Int J STD AIDS 1997;8(4):243-250.
  15. Roddy RE, Zekeng L, Ryan KA et al. A controlled trial of nonoxynol-9 film to reduce male-to-female transmission of sexually transmitted diseases. New Engl J Med 1998;339(8):504-510.
  16. Kreiss J, Ngugi E, Holmes K et al. Efficacy of nonoxynol 9 contraceptive sponge use in preventing heterosexual acquisition of HIV in Nairobi prostitutes. JAMA 1992;268(4):477-82.
  17. Van Damme, Lut; Ramjee, Gita; Alary, Michel et al. Effectiveness of COL-1492, a Nonoxynol-9 Vaginal Gel, on HIV-1 Transmission in Female Sex Workers: A Randomised Controlled Trial. Lancet (09.28.02) Vol. 360; No. 9338: p. 971-977.
  18. Hoffman T, Taha TE, Martinson F et al. Adverse health event occurring during an N-9 Gel pilot study: Malawi. 13th International AIDS Conference, July 9-14, 2000, Durban, South Africa (Abstract no. TuPpC1171).
  19. "FDA Proposes New Warning for Over-the Counter Contraceptive Drugs containing Nonoxyl 9". Associated Press. (01.16.03) CDC HIV/STD/TB Prevention News Update 01/17/03
  20. Centers for Disease Control and Prevention. Dear Colleague Letter, August 4, 2000.
  21. Centers for Disease Control and Prevention. CDC Statement on study results of product containing nonoxynol-9. MMWR August 11, 2000; 49(31):717.
  22. "Vaginal Contraceptive/HIV fighter Seems Promising" Reuters Health (12.05.02)

For more information please contact Division of HIV/AIDS Epidemiology & SurveillanceCentre for Infectious Disease Prevention & ControlHealth CanadaTunney's Pasture, Postal Locator 0900B1Ottawa, ON K1A 0L2Tel: (613) 954-5169Fax: (613)

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