A two-year FHI study concludes that vaginal spermicial film is safe to use but does not confer any additional protection to women from HIV, gonorrhea or chlamydia infections beyond the protection provided by condoms. A question and answer column and summary of selective previous N-9 research are included.
FHI collaborated with the Cameroon Ministry of Public Health to conduct the study in the African country. The research, designed to assess a spermicidal film containing nonoxynol-9 (N-9), did not address whether N-9 film used alone offers STD protection. Ronald E. Roddy, MPH, an FHI epidemiologist, and Leopold Zekeng, PhD, a Cameroon ministry HIV specialist, were the principal investigators.
Latex condoms offer the best STD protection for people at risk, but many women are unable to persuade their partners to use them. FHI believes protective measures that are used and controlled by women are urgently needed.
"Unfortunately, the news is not good for women, since we had hoped N-9 might increase their available options for HIV protection," says Willard Cates Jr., MD, MPH, FHI's senior vice president for biomedical affairs. "We must accelerate research dedicated to finding new methods for women at risk of HIV and other STDs." HIV is the virus that causes AIDS.
N-9 is available worldwide in many formulations, including foams, gels, suppositories and creams. Women who use diaphragms, for example, typically apply N-9 cream or jelly to the diaphragm, and some latex condom lubricants include N-9. None of these other products were examined in the study. Also, the study only examined women and did not consider whether N-9 film protects men.
The study was supported by a $1.6 million grant from the National Institute of Allergy and Infectious Diseases (NIAID). "Correct and consistent condom use is highly effective, but women must depend on the willingness of their partners to use male condoms," says Dr. Rodney Hoff of NIAID's AIDS prevention program. "We and other public health officials are committed to developing an STD/HIV prevention method that can be controlled by women. This study is one part of that ongoing effort."
FHI believes the study is the most thorough examination to date involving an N-9 spermicide and the role spermicides play in protecting women against STDs. The finding raises doubts about the additional benefit from using N-9 film as a prophylactic against STDs with condoms. It does not alter FHI's advice to people who are at risk from infection with HIV or other STDs -- they should use latex condoms correctly and consistently. An alternative option for many women is to use the female condom, which may provide STD protection if used consistently and correctly. Abstinence or a mutually monogamous relationship between uninfected partners are the most reliable ways of preventing STD infection.
Earlier, smaller N-9 studies had suggested that N-9 may reduce the risk of bacterial STD infections, but were inconclusive about whether N-9 prevents HIV infections. The new study involved 1,292 sex workers in Cameroon who volunteered at clinics to take part in the study between March 1995 and December 1996. To be eligible, the women could not be infected with HIV at the time they entered the study. Of the eligible volunteers, 478 who were provided a contraceptive film containing N-9 and 463 who were provided a placebo film that did not contain a spermicide, completed the study.
Each woman who asked about participating in the study received counseling to discourage her from continuing as a sex worker (prostitution), an activity that places one at great risk of acquiring HIV or other STD infections.
Volunteer participants who remained at risk were given condoms and urged to use them with every act of intercourse. They received a new supply of condoms frequently, and were examined monthly and treated for infections.
"The Cameroonian study staff strongly urged volunteers to practice safer sex," says Dr. Zekeng of Cameroon. Volunteers from the cities of Yaoundé and Douala received thorough counseling and were asked to return monthly for medical attention, which FHI believes significantly reduced the risks they otherwise would have faced. "Study participants were helped to adopt protective behaviors, which reduced their rate of infection by more than 50 percent," Dr. Zekeng says.
For the women completing the study, 147,996 acts of sexual intercourse in the group using N-9 film and condoms were compared with 146,942 acts in the group provided with the placebo film and condoms. The rate of HIV transmission was nearly the same for both groups. For every 100 women using N-9 film and condoms for one year (100 woman-years), 6.7 became infected with HIV, compared with 6.6 HIV infections using the placebo film and condoms.
The comparable rates for gonorrhea infections were 33.3 infections for N-9 and condoms to 31.1 for placebo film and condoms per 100 woman-years. Infection rates for chlamydia were 20.6 for N-9 and condoms and 22.2 for placebo film and condoms per 100 woman-years.
A theoretical concern has been whether frequent use of N-9 may increase the risk of STD infections, since frequent use of the chemical may cause sores that could enhance transmission. Women in the study reported using the film more frequently than do most women who use N-9. This study did not show any increased risk of HIV or other STD infections from using N-9 film, although genital lesions (sores) did occur slightly more often among women who used N-9. There were 42.2 lesions per 100 woman-years among women using N-9 and condoms, compared with 33.5 lesions among women using the placebo film and condoms.
The study has certain limitations. Because of the paramount concern for the safety of participants, they were counseled to use condoms every time they had sex, the only proven method of protection. Since few women reported using film without condoms, the study cannot conclusively address whether N-9 film alone offers any protection from HIV or other STDs.
Worldwide, about two thirds of all HIV-infected people live in the sub-Saharan region of Africa. One benefit of the study is that it demonstrates that HIV prevention research among people at high risk of infection can be done according to the highest ethical standards.
The film used in the study is made by Apothecus Pharmaceutical Corp., Oyster Bay, NY and is available under the brand name of VCF Vaginal Contraceptive Film.
N-9 Contraceptive Film and the Risk of STDs
The following questions and answers are grouped to address typical questions involving general information about N-9; the recent study by FHI and the Cameroon Ministry of Public Health; and the public health policy implications.
General information
What is nonoxynol-9 (N-9)?
Nonoxynol-9 (N-9) is a detergent-like chemical that has been used for more than 40 years in vaginal products to prevent pregnancy. N-9 prevents pregnancy by disrupting the outer surface of sperm, resulting in its death. Because N-9 kills sperm, it is known as a spermicide.
What products contain N-9?
In the United States, N-9 is found in a variety of vaginal spermicides including gels, creams, foams, suppositories, and film. Some of these products are meant to be used by themselves and others are meant to be used with a diaphragm or cervical cap. In other countries, N-9 is also found in spermicidal foaming tablets. N-9 is also added to certain lubricated condoms.
Do all spermicides contain N-9?
No, but most spermicidal products sold in the United States use this chemical. Other common spermicides used around the world are menfegol, a chemical used in spermicidal foaming tablets (widely used in Asia) and benzalkonium chloride (BZK), the ingredient widely used in products manufactured in France.
Is N-9 safe to use as a contraceptive?
Yes. In 1980, based on three decades of clinical experience, the U.S. Food and Drug Administration (FDA) determined that N-9 is safe and effective as a vaginal contraceptive. The safety of N-9 for vaginal use is based both on animal safety testing and on the absence of reported adverse reactions over decades of experience in humans using N-9 containing spermicidal products for contraception. For some women, N-9 causes vaginal itching and burning, which ceases when they stop using the product. N-9 may also cause similar symptoms in male sexual partners.
Are all N-9 products the same?
No. These products are available in different formulations, as gels, creams, foams, suppositories, and film. Also, spermicidal products on the market use different concentrations of N-9 (ranging from 52.5 mg to 150 mg for a typical dose). The film used in the FHI Cameroon N-9 film trial contains 70 mg of N-9.
Cameroon study results
Why are scientists examining N-9, a contraceptive, as a way to prevent STDs?
In the laboratory, N-9 kills HIV and other STD pathogens by disrupting the outer coat of the viruses and bacteria that cause the diseases, thereby killing these organisms. Also, small studies among people using N-9 have suggested that the contraceptive may protect against STDs. However, the ability of N-9 to prevent HIV or other infections in actual use had not been rigorously studied.
Another concern about the use of N-9 to prevent STDs is whether frequent use of N-9, or use in high concentrations, may actually increase the risk of STD transmission. Frequent use or high concentrations can irritate the cells that line the vagina and cervix (epithelial disruption) causing inflammation, which could theoretically lead to easier access by HIV or other microorganisms.
What did the FHI Cameroon study conclude about N-9 and STD infections?
This two-year study concluded that using N-9 film in settings where a high percentage of sex acts were protected by condoms does not offer women any protection against HIV, gonorrhea or chlamydia, in addition to that protection conferred by condoms alone. The study also concluded that using N-9 did not increase the risk of being infected by these STDs. The study could not determine if spermicidal film used alone offers STD protection.
Have these results been published in a scientific journal?
Not yet. A careful epidemiological analysis of the study data has only recently been completed, and this analysis has not yet been published. As with all FHI research, our findings will be submitted to appropriate peer-review scientific journals to be considered for publication. Because this study gives new, vitally important insights into N-9 use and STD prevention, FHI believes its findings should be made available immediately, so that women who might depend upon N-9 for STD protection are aware of this research.
How was the study conducted to reach these conclusions?
The study involved 1,292 sex workers (prostitutes) in Cameroon who volunteered at clinics to take part in the study between March 1995 and December 1996. All women who considered volunteering were strongly encouraged to discontinue their risky behavior (multiple partners), since this places them at great risk for STD infection. Those who continued their risky behavior and who were enrolled in the study were given condoms frequently, and urged to use them with every act of intercourse.
To be eligible, women could not be infected with HIV when enrolled. Volunteer women in the study were assigned to use either the N-9 film or a placebo (inactive) film, prior to having sexual intercourse. The difference between the two films was explained to them, but participants did not know whether they were using N-9 film or the placebo. The volunteers were periodically assessed for infection with HIV or other STDs, and were asked about any symptoms that might be ascribed to film use.
Of the eligible volunteers, 478 completed the study using a contraceptive film containing N-9 and 463 completed the study using a placebo film that did not contain the spermicide. Based on a careful statistical analysis that considered numerous factors, including the number of sexual acts and whether condoms were also used, a rate of STD transmission was determined for each group and these rates were compared.
Were study participants paid?
No. Participants received free medical examinations, care and counseling, free condoms and N-9 or placebo film, and were reimbursed modest transportation costs to clinics.
Who conducted the study?
The study was conducted by research scientists at the Cameroon Ministry of Public Health and Family Health International, a nonprofit research organization that specializes in reproductive health. It was sponsored by the U.S. National Institute of Allergy and Infectious Diseases (NIAID).
Who approved this study?
The scientific importance of the study was reviewed and approved by a group of non-government scientists who recommended that NIAID fund the study. Prior to starting the study, the study protocol was reviewed and approved by ethical review boards in Cameroon and at Family Health International. At FHI, a Protection of Human Subjects Committee monitors all research involving people. The eight voting members of the FHI panel are not FHI employees and come from a variety of professional backgrounds, including law, consumer interests and the clergy.
In addition, NIAID reviewed the study to assure that it met U.S. government regulations for biomedical research. To assure that the study was being conducted in an ethical manner and that the volunteers were not being exposed to undue risks, intermediate results during the course of the research were reviewed by NIAID's independent Data and Safety Monitoring Board, which is composed of scientists from universities and other institutions that were not involved in the study. The U.S. Food and Drug Administration (FDA) was not asked to approve this study because the manufacturer was not seeking specific FDA approval for use of this film in preventing HIV.
Who paid for this study, and how much did it cost?
The study was financed with a $1.6 million grant from the U.S. National Institute of Allergy and Infectious Disease (NIAID). The U.S. Agency for International Development and the Mellon Foundation provided financial support for development of the study.
Why was the study done in Africa and not in the United States?
In general, research involving infectious disease is conducted among people who are most exposed to the disease. Two of every three HIV-infected people worldwide live in sub-Saharan Africa. Among sex workers in sub-Saharan Africa, the risk of HIV infection is especially high. Because of the study's paramount concern for encouraging condom use and reducing the risk of infection, a desirable consequence of doing the study in Cameroon was to promote prevention strategies among women who are at great risk of HIV infection. Conducting the study in Cameroon not only improves scientific quality, but reduces the risk of HIV and other STD infections for participants.
Why was the N-9 contraceptive film studied, and not other N-9 products?
The N-9 film was chosen because it offers a low dose of N-9 (70 mg of N-9), thereby minimizing potential irritation to the vaginal tissue. Also, it is already available over the counter in the U.S., has a good safety profile, and it is relatively easy to use. The relatively low cost of the product suggested that it had a better chance of being available for use in developing countries such as Cameroon if it were found to be effective in preventing STDs. The film used in the study is manufactured by Apothecus Pharmaceutical Corp., a U.S. company based in Oyster Bay, NY. In the United States, the film is available over-the-counter in more than 25,000 drug stores and pharmacies and is provided by more than 6,000 family planning clinics, according to the company. The film sells under the brand name of VCF Vaginal Contraceptive Film.
Public health implications
What are the implications of this study for people at risk of HIV and other STDs?
Unfortunately, this study is not encouraging for people at risk of STDs, especially for women who cannot persuade their partners to use latex condoms. For these women, the female condom is one option that may provide STD protection if used consistently and correctly. FHI believes research to develop new options for protecting people from HIV and other STDs is urgently needed.
Anyone at risk of STDs should be aware that correct and consistent use of latex condoms is considered the best protective measure. Abstinence and a mutually monogamous relationship between uninfected partners are considered the most reliable ways of avoiding infection.
What does the U.S. Centers for Disease Control and Prevention (CDC) currently recommend regarding the prevention of HIV infection?
Currently, the CDC recommends that latex condoms with or without spermicides should be used to prevent HIV transmission among sexually active individuals at risk. FHI strongly supports this recommendation. No data currently exist to indicate that condoms lubricated with spermicides are more effective than other lubricated condoms in protecting against transmission of HIV and other STDs.
Are there other studies of N-9 products in progress?
Yes. A study is under way in Kenya to evaluate the efficacy of a low-dose N-9 gel in preventing HIV transmission. Another study of the same N-9 gel, sponsored by the Joint United Nations Programme on HIV/AIDS (UNAIDS) program, is also under way in several countries in Africa and Asia. A preliminary study to determine the safety of N-9 gel when used rectally is under way in the United States.
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