Nonoxynol-9 May Increase Risk of HIV Infection; Group Calls on Manufacturers to Remove Substance From Condoms, Lubricants

The spermicide nonoxynol-9 is not effective as a means of protection against HIV infection and may actually increase a woman's odds of contracting the virus, according to a study published in the Sept. 28 issue of the Lancet. Dr. Lut Van Damme of the Institute of Tropical Medicine in Antwerp, Belgium, and colleagues conducted a randomized, placebo-controlled, triple-blinded phase II/III trial of 765 female sex workers at four sites in Benin, Cote d'Ivoire, South Africa and Thailand to determine whether the gel form of the spermicide was protective against HIV transmission. Previous studies of nonoxynol-9, which was shown to prevent simian immunodeficiency virus infection in macaques and in vitro lab experiments, reached mixed conclusions. The women, who were recruited from sexually transmitted disease clinics, were assigned to one of two groups -- those receiving nonoxynol-9 and those receiving a placebo gel -- and were followed for 48 weeks. The women were tested for HIV and received a full reproductive health exam at each follow-up visit. The women were provided with either the nonoxynol-9 gel and condoms or a placebo gel and condoms and were also asked to record their sex acts between visits, providing details about the nature and frequency of the acts and their contraceptive use. Funding was provided by UNAIDS, and the study's design was approved by the agency as well as by national ethics boards in all four nations and the CDC.

Results
Among the 376 women using nonoxynol-9, there were 59 HIV seroconversions during the follow-up period, compared to 45 seroconversions among the 389 women using the placebo gel. The HIV incidence per 100 woman years was 14.7 for the women using nonoxynol-9 and 10.3 for the placebo group. Women who reported using nonoxynol-9 more than the mean of 3.5 applications per working day were almost twice as likely to acquire HIV compared to women who were in the placebo group. HIV risk did not vary between women who used nonoxynol-9 less frequently and those in the placebo group. According to the authors, this suggests that nonoxynol-9 "has an adverse effect on vaginal integrity when used frequently," thereby increasing a woman's susceptibility to HIV infection. They added that "nonoxynol-9 no longer has a part to play in HIV prevention," concluding, "Although efforts to promote condoms should be increased, research on additional HIV prevention methods, such as other female-controlled methods, microbicides and vaccines, should be reinforced" (Van Damme et al., Lancet, 9/28).

Microbicide Research Must Continue
The study by Van Damme and colleagues is "not good news in the fight to develop strategies that prevent acquisition of HIV and other sexually acquired infection," Dr. David Wilkinson of the University of South Australia writes in an accompanying commentary. He states that confirmation that nonoxynol-9 is effective in fighting HIV was "badly wanted to provide another option in the limited range of prevention strategies currently available under the control of women." However, he says that "there is some good news"; there are now "definitive answers" to the lingering questions over HIV and nonoxynol-9 thanks to clinical testing and research. Those studies have also provided insight into how to conduct effective trials of vaginal microbicides among women in resource-poor settings, he writes. "It is vitally important that the global effort to develop an effective vaginal microbicide that reduces the risk of acquisition of HIV (and preferably other sexually acquired infections) among women does not lose any momentum as a result of the negative results" of the study, Wilkinson says, concluding, "The concept is sound, the need is great and many important lessons have been learned: the search continues" (Wilkinson, Lancet, 9/28).

Coalition Calls on Manufacturers to Remove N-9 From Condoms, Lubricants
In related news, a "broad-based" coalition of more than 85 scientists and health groups, calling itself the "Call to Discontinue N-9 for Rectal Use," yesterday called on several manufacturers to voluntarily cease adding nonoxynol-9 to sexual lubricants and condoms, the San Jose Mercury News reports (Lyons/Ostrov, San Jose Mercury News, 9/26). "We are concerned that many people mistakenly believe that nonoxynol-9 provides extra protection against HIV and STDs ... when in fact studies show that nonoxynol-9 increases risk of infection when it is used rectally," Lori Heise, director of the Global Campaign for Microbicides, which is leading the campaign, said (Reuters/New York Post, 9/27). Heise said that nonoxynol-9 is still safe if the primary intent for use is as a contraceptive during vaginal sex and not as a preventive measure for STDs (Reuters Health, 9/26). The coalition states in its call to action, "We are not calling for the removal of N-9 contraceptive products designed exclusively for vaginal use because they remain an important contraceptive option for women who are at low risk of HIV infection or other STDs" (Global Campaign for Microbicides letter, 9/26). According to the coalition, 42% of all condoms sold in the United States are lubricated with nonoxynol-9, and 41% of gay men said that they had "actively sought out" lubricants containing the substance. In addition, both the CDC and WHO have recommended against using nonoxynol-9 to prevent HIV transmission, the group notes. Some condom and lubricant manufacturers have already removed the substance from their products. However, the three largest manufacturers -- Ansell, maker of Lifestyles condoms; Church & Dwight, maker of Trojan condoms; and SSL International, maker of Durex condoms -- have "resisted, arguing that nonoxynol-9 lubrication on condoms provides women with back-up protection against pregnancy" in the event of condom failure, the coalition states. However, Dr. Felicia Stewart, chair of the board of the Association of Reproductive Health Professionals, said, "Adding N-9 just increases risk for rectal users, while providing no clear benefit in terms of pregnancy prevention if the condom breaks." If manufacturers do not comply with the coalition's request, the group will ask stores to voluntarily remove products containing nonoxynol-9 from their shelves. The coalition -- which has support from amfAR, Planned Parenthood, the Gay & Lesbian Medical Association, the National Women's Health Network and the Association of Reproductive Health Professionals -- is also asking for "accelerated" microbicide research (Global Campaign for Microbicides release, 9/26).