a

GAO

United States Government Accountability Office

Report to Congressional Requesters

March 2005 HHS

Efforts to Research 

and Inform the Public 

about Nonoxynol-9 

and HIV

GAO-05-399
What GAO Found

United States Government Accountability Office

Why GAO Did This Study

Highlights

Accountability Integrity Reliability

www.gao.gov/cgi-bin/getrpt?GAO-05-399.

To view the full product, including the scope 

and methodology, click on the link above. 

For more information, contact Marjorie Kanof 

at (202) 512-7114. 

Highlights of GAO-05-399, a report to 

congressional requesters 

March 2005

HHS

Efforts to Research and Inform the Public 

about Nonoxynol-9 and HIV 

Federal agencies have undertaken a variety of efforts to research N-9 as a 

potential microbicide—including conducting, funding, or reviewing studies 

on the safety and effectiveness of N-9. In the 1990s, CDC and NIH conducted 

and funded research on the effectiveness and safety of N-9 as a microbicide 

to prevent HIV infection. For example, in 1996 CDC and others began a 

4-year study on the effectiveness of an N-9 vaginal contraceptive product in 

preventing the transmission of sexually transmitted diseases, including HIV. 

The results of the research by the agencies during this period were 

inconsistent—some research indicated that N-9 reduced the incidence of 

HIV while other research suggested that frequent use of N-9 may increase 

the risk of contracting the virus. Then in 2000, the preliminary results of a 

major clinical study suggested more strongly that N-9 vaginal contraceptive 

products did not prevent HIV infection and may increase the risk of infection 

among frequent users. As a result of the study, CDC and NIH stopped 

conducting and funding research on N-9 as a microbicide out of concern for 

participants’ safety. FDA continued to review available research on the 

safety of N-9 as part of its regulation of vaginal contraceptive products and, 

in 2003, proposed new warning labels for N-9 vaginal contraceptive 

products. As of March 2005, FDA was also in the process of developing a 

proposal for new warning labels for N-9 condoms. As of that date, FDA had 

not finalized the new warning labels for N-9 vaginal contraceptive products 

and had not proposed new warning labels for N-9 condoms. Representatives 

from two manufacturers of N-9 contraceptive products have reviewed 

research on N-9’s safety for the purpose of commenting on FDA’s proposed 

warning labels. 

The information CDC and FDA have provided to the public about the use of 

N-9 as a microbicide has been, at times, inconsistent. In the early 1990s, 

CDC cautioned that there was insufficient information to conclude that N-9 

may prevent HIV transmission. By 1998, in response to new research, the 

agency informed the public that N-9 vaginal contraceptive products did not 

prevent HIV. During the same period, FDA also cautioned that N-9 had not 

been proven to prevent HIV transmission, but in 1999, a brochure posted on 

its Web site stated that N-9, along with a condom, may be used to prevent 

HIV transmission. By 2000, CDC had responded to new research findings and 

had revised its educational publications to state that N-9 may actually 

increase the risk of contracting HIV when used frequently. In contrast, FDA 

did not revise the brochure on its Web site that stated that some experts 

believe N-9 may prevent HIV and suggested using N-9 along with a condom. 

FDA left this information on its Web site until these statements were deleted 

in September 2003 when FDA officials realized the information was 

inconsistent with proposed warning labels. 

In commenting on a draft of this report, the Department of Health and 

Human Services (HHS) provided clarification that GAO incorporated where 

appropriate. 

Preventing the transmission of HIV, 

the virus that causes AIDS, is an 

important public health challenge. 

Researchers have sought to 

develop a microbicide—a 

substance to help users protect 

themselves against HIV. In the 

mid-1980s, researchers found that 

Nonoxynol-9 (N-9), a spermicide 

found in various contraceptive 

products, showed potential as a 

microbicide. However, more 

recent studies raised concerns that 

N-9 may increase certain users’ risk 

of contracting HIV. 

GAO was asked to describe federal 

agencies’ and contraceptive 

product manufacturers’ actions 

related to N-9 and HIV. In this 

report, GAO reviewed (1) the 

efforts by federal agencies and 

manufacturers of contraceptive 

products to assess the safety of N-9 

and its effectiveness as a 

microbicide for preventing HIV 

transmission and (2) the 

information provided to the public 

about the safety of N-9 and its 

effectiveness as a microbicide. 

GAO reviewed journal articles, 

Federal Register notices, product 

packaging, educational materials, 

and other documents. GAO also 

interviewed officials from the 

Centers for Disease Control and 

Prevention (CDC), the Food and 

Drug Administration (FDA), the 

National Institutes of Health (NIH), 

and selected manufacturers of N-9 

contraceptive products. 
Page i GAO-05-399 Nonoxynol-9 and HIV

Contents

Letter 1

Results in Brief 3

Background 5

Federal Agencies Have Researched the Safety and Effectiveness of 

N-9 as a Microbicide, While Manufacturers Reviewed Its Safety 8

The Information Provided to the Public about the Use of N-9 as a 

Microbicide Has Been, at Times, Inconsistent 14

Some Manufacturers and Public Health Organizations Have Stopped 

Producing and Distributing N-9 Condoms 19

Concluding Observations 19

Agency Comments 20

Appendixes

Appendix I: Timeline of Selected Events and Publications Related to 

N-9’s Potential Use as a Microbicide, 1990–2004 23

Appendix II: Comments from the Department of Health and Human 

Services 24

Appendix III: GAO Contact and Staff Acknowledgments 28

GAO Contact 28

Acknowledgments 28
Contents

Page ii GAO-05-399 Nonoxynol-9 and HIV

Abbreviations

CDC Centers for Disease Control and Prevention

CDER Center for Drug Evaluation and Research

CDRH Center for Devices and Radiological Health

FDA Food and Drug Administration

HHS Department of Health and Human Services

MMWR Morbidity and Mortality Weekly Report

N-9 Nonoxynol-9

NIH National Institutes of Health

PPFA Planned Parenthood Federation of America

STD sexually transmitted disease

WHO World Health Organization

This is a work of the U.S. government and is not subject to copyright protection in the 

United States. It may be reproduced and distributed in its entirety without further 

permission from GAO. However, because this work may contain copyrighted images or 

other material, permission from the copyright holder may be necessary if you wish to 

reproduce this material separately.
Page 1 GAO-05-399 Nonoxynol-9 and HIV

United States Government Accountability Office

Washington, D.C. 20548

A

March 31, 2005 Letr

The Honorable Mark Souder

Chairman

Subcommittee on Criminal Justice, Drug Policy and Human Resources

Committee on Government Reform

House of Representatives

The Honorable Tom Coburn

United States Senate

The Honorable Joseph Pitts

House of Representatives

The Honorable David Weldon

House of Representatives

Preventing the transmission of HIV, the virus that causes AIDS, is an 

important public health challenge. The Centers for Disease Control and 

Prevention (CDC) has reported that an estimated 850,000–950,000 HIV 

positive people live in this country, including 180,000–280,000 who do not 

know they are infected.1

Researchers have sought to develop a microbicide2

 that could be used to 

prevent HIV transmission. If developed, a microbicide could be a topically 

applied substance to help users protect themselves against HIV or other 

sexually transmitted diseases (STD). One of the advantages of a 

microbicide over other methods of preventing HIV—such as condoms or 

mutual monogamy—would be that an individual could use the microbicide 

without the cooperation of a sexual partner. 

1

 Centers for Disease Control and Prevention, Basic Statistics: HIV Estimate, 

http://www.cdc.gov/hiv/stats.htm (downloaded Jan. 31, 2005).

2

 A microbicide is any agent that kills microbes such as bacteria, fungi, and parasites. Some 

microbes are capable of causing disease.
Page 2 GAO-05-399 Nonoxynol-9 and HIV

In the mid-1980s researchers found that Nonoxynol-9 (N-9), a widely 

available spermicide3

 found in various over-the-counter4 contraceptive 

productsincluding some condoms and certain vaginal contraceptive 

products such as foams and gelsshowed promise as a potential 

microbicide for STDs, including HIV.5

 In 1988, the Surgeon General, in 

collaboration with CDC, distributed brochures to 107 million U.S. 

households that stated that based on laboratory tests, condoms with N-9 

may provide additional protection against HIV.6

 Around this time, it was 

also widely reported in newspapers and journals that it was advisable to 

use contraceptive products with N-9 because it might help prevent HIV.7

 

However, more recent studies have raised concerns that N-9 vaginal 

contraceptive products may not be effective against HIV and may in fact 

increase certain users’ risk of contracting the virus. Public health 

organizations have also expressed concerns that consumers may use 

condoms lubricated with N-9 (N-9 condoms) for anal intercourse in order 

to protect themselves against HIV without knowing the degree to which the 

use of such condoms may put them at risk. Because of the potential risks 

involved, the use of N-9 is an important public health issue—one that 

involves CDC, the Food and Drug Administration (FDA), and the National 

Institutes of Health (NIH) and their research, regulatory actions, or efforts 

to educate the public about N-9 and HIV. 

You asked us to describe federal agencies’ and contraceptive product 

manufacturers’ actions related to N-9 and HIV. This report describes 

3

 A spermicide is a chemical compound that inactivates sperm by damaging their cell 

membranes.

4

 Over-the-counter refers to drug products sold without a prescription.

5

 For example, N-9, available over-the-counter for almost 50 years, was first demonstrated to 

be effective against HIV in a laboratory study in 1985. D.R. Hicks, L.S. Martin, J.P. Getchell, 

et al., “Inactivation of HTLV-III/LAV-Infected Cultures of Normal Human Lymphocytes by 

Nonoxynol-9 In-vitro,” The Lancet (1985).

6

 C.E. Koop, Surgeon General, and Centers for Disease Control, Public Health Service, 

Understanding AIDS (1988).

7

 For example the New York Times reported in 1987 that “Additional protection is gained by 

applying spermicides containing nonoxynol-9, which kills the AIDS virus.” See J.E. Brody, 

“Personal Health,” New York Times (Mar. 4, 1987). That same year, the Journal of the 

American Medical Association reported that the Surgeon General recommended that 

condoms be lubricated with N-9 “which some evidence shows may inhibit the virus.” See 

C.E. Koop, “Physician Leadership in Preventing AIDS,” Journal of the American Medical 

Association, vol. 258 (1987).
Page 3 GAO-05-399 Nonoxynol-9 and HIV

(1) efforts by federal agencies and manufacturers of contraceptive 

products to assess the safety of N-9 and its effectiveness as a microbicide 

for preventing HIV transmission, (2) the information federal agencies and 

manufacturers of contraceptive products have provided to the public about 

the safety of N-9 and its effectiveness as a microbicide, and (3) decisions by 

manufacturers and public health organizations that may have affected the 

availability of N-9 condoms. 

To describe the efforts of federal agencies and manufacturers of 

contraceptive products to assess the safety of N-9 and its effectiveness as a 

microbicide for preventing HIV transmission, we reviewed reports, journal 

articles, Federal Register notices, agency Web sites, and other documents 

related to N-9 and HIV. We interviewed officials from CDC, FDA, and NIH. 

We also interviewed officials from the three largest condom manufacturers 

in the United States—Armkel, LLC; SSL International; and Ansell Limited—

which account for an estimated 98 percent of U.S. condom retail sales; as 

well as officials from two manufacturers of other N-9 contraceptive 

products—Apothecus Pharmaceutical Corporation and Johnson & Johnson 

Consumer Companies, Incorporated. To describe the information federal 

agencies and manufacturers of contraceptive products have provided to 

the public about the safety of N-9 and its effectiveness as a microbicide, we 

reviewed articles, pamphlets, agency and manufacturer Web sites, 

manufacturer product packaging, and other educational materials related 

to N-9 and HIV. We also interviewed officials from CDC, FDA, and the 

manufacturers of contraceptive products. Because concerns about the 

safety of N-9 in preventing HIV first began to surface around 1990, we 

focused our review on efforts to research and provide public information 

on N-9 and HIV from 1990 to the present. To describe decisions by 

manufacturers and public health organizations that may have affected the 

availability of N-9 condoms, we interviewed officials from CDC; FDA; NIH; 

three national reproductive health organizations—Planned Parenthood 

Federation of America (PPFA), Family Health International, and the Global 

Campaign for Microbicides; and the three largest condom manufacturers in 

the United States. We also interviewed a researcher who conducted a key 

clinical study on N-9 and HIV. We performed our work from October 2003 

through March 2004 and August 2004 through March 2005 in accordance 

with generally accepted government auditing standards.

Results in Brief Federal agencies have undertaken a variety of efforts to research N-9 as a 

potential microbicide—including conducting, funding, or reviewing studies 

on the safety and effectiveness of N-9, and manufacturers have reviewed 
Page 4 GAO-05-399 Nonoxynol-9 and HIV

research on the safety of N-9. In the 1990s, CDC and NIH conducted and 

funded research on the effectiveness and safety of N-9 as a microbicide to 

prevent HIV infection. For example, in 1996 CDC and others began a 4-year 

study on the effectiveness of an N-9 vaginal contraceptive product in 

preventing the transmission of STDs, including HIV. In the 1990s, NIH 

funded a range of laboratory and clinical studies of N-9 as a possible 

microbicide for HIV. During this time, FDA reviewed research on N-9 as 

part of its regulatory process for reviewing the safety and effectiveness of 

N-9 as a vaginal contraceptive. The results of the research conducted, 

funded, and reviewed by the agencies during this period were 

inconsistent—some research indicated that N-9 reduced the incidence of 

HIV while other research suggested that frequent use of N-9 may increase 

the risk of contracting the virus. Then in 2000, the preliminary results of a 

major clinical study suggested more strongly that N-9 vaginal contraceptive 

products did not prevent HIV infection and may increase the risk of 

infection among frequent users. As a result of the study, CDC and NIH 

stopped conducting and funding research on N-9 as a microbicide out of 

concern for participants’ safety. FDA continued to review available 

research on the safety of N-9 as part of its regulation of vaginal 

contraceptive products and, in 2003, proposed new warning labels for N-9 

vaginal contraceptive products. As of March 2005, FDA was also in the 

process of developing a proposal for new warning labels for N-9 condoms. 

As of that date, FDA had not finalized the new warning labels for N-9 

vaginal contraceptive products and had not proposed new warning labels 

for N-9 condoms. Representatives from two manufacturers of N-9 

contraceptive products have reviewed research on N-9’s safety in preparing 

comments on FDA’s proposed warning labels. 

The information CDC and FDA have provided to the public about the use of 

N-9 as a microbicide has been, at times, inconsistent. In the early 1990s, 

CDC cautioned that there was insufficient information to conclude that N-9 

may prevent HIV transmission. By 1998, in response to new research, the 

agency informed the public that N-9 vaginal contraceptive products did not 

prevent HIV. For example, CDC’s 1993 STD treatment guidelines cautioned 

that women should not assume that N-9 vaginal contraceptive products 

protect them against HIV, and the updated 1998 guidelines stated that 

vaginal contraceptive products offer no protection against HIV infection. 

During the same period, FDA also cautioned that N-9 had not been proven 

to prevent HIV transmission, but in 1999, a brochure on its Web site 

suggested that N-9, along with a condom, may be used to prevent HIV 

transmission. By 2000, CDC had responded to new research findings and 

had revised its educational publications to state that N-9 may actually 
Page 5 GAO-05-399 Nonoxynol-9 and HIV

increase the risk of contracting HIV when used frequently. In contrast, 

FDA did not revise the brochure on its Web site that stated that some 

experts believe N-9 may prevent HIV and suggested using N-9 along with a 

condom. FDA left this information on its Web site until these statements 

were deleted in September 2003 when FDA officials realized this 

information was inconsistent with the proposed warning labels for N-9 

vaginal contraceptive products. The three largest condom manufacturers 

have also taken steps to inform the public about N-9 and HIV. For example, 

one condom manufacturer has informed its consumers that N-9 does not 

prevent HIV transmission and may increase some users’ risk of contracting 

HIV. In contrast, other manufacturers of contraceptive products that we 

interviewed have not taken such steps.

In recent years, some key manufacturers and public health organizations 

have stopped producing, distributing, or promoting N-9 condoms, and the 

percentage of these condoms on the market is reported to have decreased. 

In January 2004, one of the three largest condom manufacturers stopped 

producing N-9 condoms. Similarly, according to representatives from 

PPFA, the organization stopped manufacturing N-9 condoms in 2002. A 

representative from PPFA explained that this decision was based on a 

concern about the safety issues associated with N-9 condoms. Like PPFA, 

another key public health organization we interviewed has begun to 

recommend against the use of N-9 condoms.

In commenting on a draft of this report, the Department of Health and 

Human Services (HHS) provided clarification that GAO incorporated 

where appropriate. 

Background N-9 was developed as a contraceptive and is the only spermicide available 

in the United States. It is found in a variety of over-the-counter vaginal 

contraceptive products—including creams, foams, gels, and 

suppositories—and on N-9 condoms. Vaginal contraceptive products that 

contain N-9 have been sold over-the-counter in the United States for almost 

50 years. N-9 condoms have been available over-the-counter in the United 

States since the early 1980s. 

Federal Agency 

Responsibilities

Three federal agencies within HHS—CDC, NIH, and FDA—have 

responsibilities that affect the public’s use of N-9 contraceptive products.
Page 6 GAO-05-399 Nonoxynol-9 and HIV

CDC CDC is responsible for conducting and reviewing research related to public 

health issues and disseminating this information to state public health 

agencies, medical professionals, and the public. CDC shares information, 

for example, on diseases such as HIV and uses a variety of means to do this, 

including publications such as the Morbidity and Mortality Weekly Report

(MMWR) 8 and treatment guidelines. It also provides information through 

its Web site and in letters issued directly to state health departments and 

other public health professionals.

NIH NIH, which comprises 27 separate institutes and centers, conducts 

research in its own laboratories and funds research in universities, medical 

schools, hospitals, and other research institutions. Some of this research 

investigates drugs used to prevent and treat various diseases, including 

HIV. In order to provide information to the public on various health issues, 

NIH may post the results of its research on its Web site and sometimes 

publishes summary reports on various research topics.

FDA FDA is responsible, among other things, for regulating the manufacture and 

sale of drugs and medical devices sold in the United States. FDA also 

regulates the labeling information provided by manufacturers of drugs and 

medical devices. FDA also seeks to educate the public about the products 

it regulates and uses a variety of means, including pamphlets, Web site 

information, and the FDA Consumer magazine9

 to do this. Within FDA, 

two centers are involved in the review of N-9 contraceptive products—the 

Center for Drug Evaluation and Research (CDER), which oversees vaginal 

contraceptive drug products, and the Center for Devices and Radiological 

Health (CDRH), which oversees condoms, including N-9 condoms.

FDA reviews the active ingredients in specific categories of drugs that were 

sold over-the-counter in the United States prior to 1975 through a process 

known as the “monograph process.” 10 Under the monograph process, FDA 

establishes the conditions under which specific categories of drugs, rather 

than specific products, are generally recognized as safe and effective and 

8

 CDC’s MMWR is a series of articles on public health issues that are based on reports sent to 

CDC by state and territorial health departments.

9 FDA Consumer is a publication intended to educate the public as well as health care 

providers about products that FDA regulates.

10 FDA also refers to the monograph process as the Over-the-Counter Drug Review.
Page 7 GAO-05-399 Nonoxynol-9 and HIV

not misbranded.11 Examples of categories of drugs subject to the 

monograph process include antacids and certain cold and cough remedies. 

When FDA completes the monograph process, it issues a final monograph 

that describes labeling indications, warnings, and directions for use, among 

other things. Prior to the issuance of a final monograph, FDA policies 

allow over-the-counter drugs to stay on the market. However, FDA may 

pursue regulatory actions against these drugs—such as requiring labeling 

changes—if the agency determines that the failure to act poses a potential 

health hazard to consumers.12 

Since N-9 was available over-the-counter prior to 1975, it is the subject of a 

monograph review for a category of drugs called vaginal contraceptive 

drug products.13 As of March 2005, FDA had not issued a final monograph 

for this category of drugs.14 Although some condoms on the market are 

lubricated with N-9, these N-9 condoms are not subject to the monograph 

review process for vaginal contraceptive products because FDA regulates 

these products as medical devices.15

11 In the first step of the three-step monograph process, an Advisory Review Panel of 

nongovernment experts reviews data on active ingredients and provisionally classifies the 

ingredients as Category I (safe and effective), Category II (not safe and effective), or 

Category III (more data needed). The panel's report is published as an advance notice of 

proposed rule making in the Federal Register. In the second step, FDA publishes a tentative 

final monograph or proposed rule for the particular category of drugs. In the third step, 

FDA publishes a final monograph or final rule containing FDA's final conclusions. See 21 

C.F.R. § 330.10. 

12 FDA Compliance Guide No. 7132b.15, March 1995.

13 In the rest of this report, we refer to FDA’s category of “vaginal contraceptive drug 

products” as vaginal contraceptive products.

14 The first step of the monograph process for this category of drugs occurred in 1980 when 

FDA published the report of the Advisory Review Panel on over-the-counter contraceptives 

and other vaginal drug products, which provisionally classified N-9 as safe and effective as a 

contraceptive. See 45 Fed. Reg. 82014 (Dec. 12, 1980). The second step occurred in 1995, 

when FDA issued a proposed rule that required additional clinical research to determine the 

contraceptive effectiveness for different formulations of N-9. See 60 Fed. Reg. 6892 (Feb. 3, 

1995). According to FDA officials, the issuance of the final monograph is pending its review 

of a large contraceptive efficacy study that was published in March 2004. FDA is allowing 

the continued marketing of vaginal contraceptive products pending completion of this 

review.

15 See 21 C.F.R. § 884.5300 and 21 C.F.R. § 884.5310.
Page 8 GAO-05-399 Nonoxynol-9 and HIV

Federal Agencies Have 

Researched the Safety 

and Effectiveness of 

N-9 as a Microbicide, 

While Manufacturers 

Reviewed Its Safety 

Federal agencies have undertaken a variety of efforts to research the safety 

and effectiveness of N-9 as a microbicide. This research included funding, 

conducting, or reviewing studies on the safety and effectiveness of N-9 as a 

microbicide. It was largely conducted until 2000, when the preliminary 

results of a major clinical study prompted CDC and NIH to halt further 

research on N-9 as a microbicide because of safety concerns. FDA—as 

part of its regulation of vaginal contraceptive products—continued to 

review research on the safety of N-9 and proposed new warning labels for 

vaginal contraceptive products in 2003. Manufacturers reviewed the safety 

of N-9 for the purpose of commenting on the proposed warning labels.

Federal Agencies 

Researched the Safety and 

Effectiveness of N-9 as a 

Microbicide until 2000

During the 1990s, three federal agencies—CDC, NIH, and FDA—funded, 

conducted, or reviewed medical research to determine whether N-9 was 

safe and effective as a microbicide. CDC, as part of its public health efforts 

to prevent the spread of HIV, conducted and funded research involving N-9. 

For example, in 1996, CDC and others began a major 4-year study on the 

effectiveness of N-9 vaginal contraceptive products in preventing the 

transmission of STDs, including HIV, among female sex workers located in 

four countries. In addition, CDC compiled a bibliography of research on 

potential microbicides conducted through September 1996.16 Containing 

abstracts of over 55 safety and effectiveness studies and other reviews of 

N-9 vaginal contraceptive products and N-9 condoms, the bibliography was 

intended as a resource for clinicians, researchers, and public health 

specialists interested in microbicide research. 

Like CDC, NIH conducted and funded research during the 1990s on N-9’s 

safety and effectiveness as a microbicide. Within NIH, two institutes were 

primarily responsible for most of its N-9 research—the National Institute of 

Allergy and Infectious Diseases and the National Institute of Child Health 

and Human Development. NIH’s research ranged from laboratory studies of

16 Centers for Disease Control and Prevention, Guide to Microbicide Research and 

Development: HIV Infection, Selected Bibliography through September 1996. 
Page 9 GAO-05-399 Nonoxynol-9 and HIV

N-9’s effect on animal tissue to randomized clinical trials that measured the 

effect of various N-9 vaginal contraceptive products in preventing HIV 

transmission among women.17 

Although the FDA did not conduct or fund research on N-9, the agency 

reviewed research on N-9 vaginal contraceptive products as part of its 

monograph process. The agency convened an advisory committee meeting 

in 1996 to review available research on the safety and effectiveness of N-9 

as both a contraceptive and a microbicide.18 This meeting included 

presentations on a wide variety of published and unpublished research, 

including laboratory studies of N-9 and clinical studies on N-9 vaginal 

contraceptive products. The meeting also included discussion about the 

implications of this research and identified guidelines for the design of 

future studies to address concerns about dosage and formulation 

differences in the research available at the time, among other things. 

The results of the research on N-9 that federal agencies conducted, funded, 

and reviewed during the 1990s were inconsistent. For example, among the 

studies compiled in CDC’s bibliography on microbicide research, some 

found that the use of N-9 vaginal contraceptives reduced the incidence of 

HIV as well as other STDs, while other studies indicated that frequent use 

of N-9 vaginal contraceptives may have irritated subjects’ vaginal tissue, 

which may result in subjects being more susceptible to HIV infection. 

Throughout the 1990s, various reviews in clinical journals also 

characterized the results of research on N-9 as inconsistent.19 For example, 

a 1995 review in the journal AIDS noted the existence of “substantially

17 Laboratory testing is conducted to determine whether a drug has an effect on a disease in 

animals and whether it is reasonably safe for initial testing in humans. Randomized clinical 

trials are studies designed to determine the safety and effectiveness of a drug in humans by 

comparing the outcomes for a group using the drug to the outcomes for a similar group 

using a placebo or a standard therapy.

18 The meeting included representatives from the FDA advisory committees for antiinfective drugs, antiviral drugs, reproductive health drugs, and nonprescription drugs. FDA 

advisory committees are composed of academicians, clinicians, consumer group 

representatives, industry representatives, and patients or their caregivers. The committees 

provide independent advice to FDA in order to contribute to the quality of the agency's 

regulatory decision making.

19 Most of the reviewed research involved N-9 vaginal contraceptives.
Page 10 GAO-05-399 Nonoxynol-9 and HIV

different opinions” about the safety and effectiveness of N-9 when used for 

HIV prevention.20 Similarly, a 1999 commentary in the American Journal 

of Public Health noted that epidemiologic studies on N-9 were conflicting.21 

During the 1990s, reviewers of studies involving N-9 observed that several 

factors may have accounted for the inconsistency of the research results. 

For example, studies varied in terms of the dosage of N-9 and the chemical 

formulation of the contraceptive product used.22,23 Additionally, the 

different populations studied may have affected the outcomes of the 

research. For example, some studies were based on the experience of sex 

workers, who used N-9 vaginal contraceptive products with relatively 

higher frequency than the populations in other studies. Studies were also 

not always comparable to the extent that they varied in their sample sizes. 

In 2000, after the preliminary results of a major clinical study—known as 

the COL-1492 study—were reported, CDC and NIH stopped conducting and 

funding research on N-9 as a microbicide out of concern for participants’ 

safety.24 Compared to the results of earlier studies, the preliminary results 

of the COL-1492 study suggested more strongly that N-9 did not prevent 

HIV infection and, in addition, that N-9 may increase the risk of infection 

among frequent users.25 The COL-1492 study compared the use of an N-9 

vaginal contraceptive gel called COL-1492 to a vaginal moisturizer without 

N-9 among 892 sex workers in Benin, Cote d’Ivoire, South Africa, and 

20 C. Elias and L.L. Heise, “Nonoxynol-9: The Need for Policy in the Face of Uncertainty,” 

AIDS, vol. 9, no. 3 (1995).

21 P. Feldblum, S. Weir, and W. Cates, “The Protective Effect of Condoms and Nonoxynol-9 

Against HIV Infection,” American Journal of Public Health, vol. 89, no. 1 (1999).

22 Since the monograph process for over-the-counter drugs evaluates the active ingredients 

in categories of drugs rather than specific products, N-9 vaginal contraceptive products on 

the market may vary in formulation and dosage.

23 See, for example, R.L. Cook and M.J. Rosenberg, “Do Spermicides Containing Nonoxynol9 Prevent Sexually Transmitted Infections? A Meta-Analysis,” Sexually Transmitted 

Diseases, vol. 25, no. 3 (March 1998).

24 Although NIH stopped conducting and funding research on N-9 as a microbicide, it 

continued research on the effectiveness of N-9 as a contraceptive product.

25 This study was conducted primarily in locations with a high prevalence of HIV infection 

and among sex workers, who typically have multiple partners and were, therefore, 

considered high risk. The risk of becoming infected with HIV increases with the number of 

sexual partners, whether or not condoms are used, and the local prevalence of infection. 
Page 11 GAO-05-399 Nonoxynol-9 and HIV

Thailand. The preliminary results of this study indicated that the incidence 

of HIV infection among users of the N-9 vaginal contraceptive gel was 48 

percent higher than among users of the moisturizer without N-9. Moreover, 

the study showed there was little effect of N-9 vaginal contraceptive use on 

the incidence of certain other STD infections, such as gonorrhea and 

chlamydia. After the preliminary results of the COL-1492 study became 

available, officials at CDC and NIH decided to discontinue researching N-9 

as a possible microbicide for HIV. 

After 2000, FDA Continued 

to Review Research on the 

Safety of N-9 as Part of Its 

Regulation of N-9 

Contraceptive Products 

Although federal agencies stopped conducting and funding research on N-9 

as a potential microbicide in 2000, FDA continued to review research on 

the safety of N-9 as part of the agency’s regulation of vaginal contraceptive 

products under the monograph process. During this review, FDA 

considered, among other things, the recommendations of two key public 

health reports, 26 published in 2002 by CDC and by the World Health 

Organization (WHO) in collaboration with the CONRAD Program.27 The 

reports recommended that N-9 not be used to prevent HIV transmission 

and warned that frequent use of N-9 vaginal contraceptive products may 

cause genital lesions, which may increase the risk of HIV infection in 

persons at high risk for HIV. The reports also recommended that N-9 

condoms not be promoted because there was no published scientific 

evidence that N-9-lubricated condoms provide any additional protection 

against STDs compared with other condoms.28 The reports also 

recommended that N-9 contraceptive products, including both N-9 

condoms and vaginal contraceptive products, should not be used during 

anal intercourse. The WHO/CONRAD report concluded that for women at 

26 Centers for Disease Control and Prevention, “Nonoxynol-9 Spermicide Contraception 

Use – United States, 1999,” Morbidity and Mortality Weekly Report, vol. 51, no. 18 (May 

2002). World Health Organization/CONRAD, WHO/CONRAD Technical Consultation on 

Nonoxynol-9: Summary Report (June 2002). 

27 The CONRAD Program, which is a nonprofit organization, supports the development of 

methods to prevent pregnancy and STDs, including HIV/AIDS. Funded primarily by the 

Agency for International Development, the program offers both financial support as well as 

technical assistance for the various stages of product development.

28 CDC did not advise against using previously purchased N-9 condoms. However, because 

of their shorter shelf life, higher cost, association with urinary tract infections in women, 

and lack of apparent benefit compared with other lubricated condoms, CDC recommended 

against purchasing any additional N-9 condoms. 
Page 12 GAO-05-399 Nonoxynol-9 and HIV

low risk for HIV infection, the use of N-9 vaginal contraceptives remained a 

viable option.

Based on its review of this and other information, including the published 

results of the COL-1492 study,29 FDA determined that the use of N-9 vaginal 

contraceptive products may pose a potential health hazard to consumers 

and proposed new warning labels for N-9 vaginal contraceptive products in 

January 2003.30 Specifically, FDA proposed adding warning labels that 

indicate that vaginal contraceptive products with N-9 do not protect against 

HIV or other STDs and that frequent use, such as more than once a day, of 

N-9 can increase vaginal irritation, which may increase the risk of 

contracting HIV from infected partners. The proposed warnings also 

indicate that the labeled products are for vaginal use only. 

As of March 2005, FDA was in the process of finalizing the rule for new 

warning labels for vaginal contraceptive products containing N-9. 

According to FDA officials, a draft of the final rule had been completed, 

and the rule had begun the clearance process within HHS. Officials told us 

that they expected the clearance process to be completed by September 

2005, after which the final rule would be published. According to FDA 

officials, the rule-making process used to establish new warning labels 

typically takes more than 2 years. 

As part of the process for establishing new warning labels for N-9 vaginal 

contraceptive products, FDA reviewed more than 150 comments submitted 

in response to the proposed warning labels. These comments ranged from 

concerns that the proposed language was not strong or specific enough to 

comments indicating that FDA had gone too far in its proposed warning. 

FDA officials also stated that 10 specific issues brought up in the public 

comments on the proposed warning labels required extensive review, 

29 While there were some differences between the published study and the preliminary 

results reported in 2000, the conclusions of the published study were consistent with those 

of the preliminary results. The published study reported that “nonoxynol-9 increased the 

risk of HIV infection compared with the placebo.” It also stated that “risk was especially 

high in women who used the study drug more than 3.5 times per day.” See L. Van Damme, et 

al., “Effectiveness of COL-1492, a Nonoxynol-9 Vaginal Gel, On HIV-1 Transmission in 

Female Sex Workers: A Randomised Controlled Trial,” The Lancet, vol. 360 (September 

2002). 

30 FDA policy states that FDA may pursue regulatory action against over-the-counter drugs 

prior to the adoption of a final monograph if the agency determines that the failure to act 

would pose a potential health hazard to consumers. See FDA Compliance Guide No. 

7132b.15, March 1995.
Page 13 GAO-05-399 Nonoxynol-9 and HIV

including comments that the labels should specifically warn against using 

vaginal contraceptive products for anal intercourse and concerns that the 

proposed warning labels might discourage women who are at low risk for 

HIV from using N-9 as a contraceptive.31 

FDA officials told us they also plan to issue guidance and proposed new 

warning labels for condoms—including warnings for N-9 condoms. They 

said they expect a draft to be issued for public comment in 2005. These 

officials noted that they considered new warning labels for N-9 condoms in 

the context of a larger initiative started in 2001 to review condom labeling 

for medical accuracy with respect to the overall effectiveness of condoms 

against STDs.32 FDA officials told us that officials from CDRH and CDER 

collaborated to ensure that the new labeling proposals for N-9 condoms 

and N-9 vaginal contraceptive products will be consistent.33 As of March 

2005, an HHS official told us that HHS had completed its review of the draft 

guidance and labels. After this review, FDA officials told us the draft would 

be sent to the Office of Management and Budget for review before being 

issued for public comment. FDA officials said that FDA expects to be able 

to issue the draft guidance and condom warning labels by May 2005. 

31 Among the more than 150 comments, FDA received a range of comments from 15 health 

and research organizations—such as the American College of Obstetricians and 

Gynecologists and Family Health International. The majority of these organizations 

supported FDA’s labeling proposal, and half of them recommended that the FDA go even 

further than saying “for vaginal use only,” either by warning that N-9 vaginal contraceptives 

should not be used for anal intercourse or by notifying consumers that there is an increased 

risk when used for anal intercourse. Four organizations stated that the warnings should be 

more specific in assuring women at low risk for HIV that N-9 can be safe and effective as a 

contraceptive. In addition to comments from health and research organizations, FDA 

received comments from two manufacturers of contraceptive products containing N-9. 

These manufacturers indicated that the proposed warning labels went too far in suggesting 

that N-9 may lead to increased HIV transmission and might discourage women who are at 

low risk for HIV from using N-9 as a contraceptive.

32 The Consolidated Appropriations Act of 2001 required FDA to examine condom labeling. 

See Pub. L. No. 106-554, App. A, § 516(b), 114 Stat. 2763, 2763A-73 (2000).

33 Officials also noted that in the past, FDA had not permitted condom labeling to claim that 

N-9 provided any additional protection against HIV or other STDs.
Page 14 GAO-05-399 Nonoxynol-9 and HIV

Manufacturers of N-9 

Contraceptive Products 

Have Researched the Safety 

of N-9 

Two manufacturers of N-9 contraceptive products that we interviewed 

have researched the safety of N-9. Specifically, they reviewed the research 

literature on the safety of N-9 in order to prepare comments in response to 

the language of FDA’s proposed warning labels for vaginal contraceptive 

products. For example, one manufacturer concluded that FDA’s proposed 

labeling—that implied a link between the use of N-9 vaginal contraceptive 

products and an increased risk of HIV transmission—was not sufficiently 

supported by the scientific literature. However, no manufacturers we 

interviewed have conducted research on N-9’s effectiveness as a 

microbicide. Manufacturers would only be required to conduct such 

research if they were to seek approval from FDA to use N-9 vaginal 

contraceptives for a new indication—such as HIV prevention. However, 

FDA officials reported that no manufacturers sought approval for a new 

indication for N-9. 

The Information 

Provided to the Public 

about the Use of N-9 as 

a Microbicide Has 

Been, at Times, 

Inconsistent 

The information CDC and FDA provided the public about the use of N-9 as 

a microbicide has been, at times, inconsistent. In the early 1990s, CDC 

cautioned that there was insufficient information to conclude that N-9 may 

prevent HIV transmission. By 1998, in response to new research, CDC 

informed the public that N-9 vaginal contraceptive products did not prevent 

HIV. During the same period, FDA also cautioned that N-9 had not been 

proven to prevent HIV transmission, but in 1999, a brochure on its Web site 

stated that N-9, along with a condom, may be used to prevent HIV 

transmission. By 2000, CDC stated that N-9 may actually increase the risk 

of contracting HIV when used frequently. FDA, in contrast, did not revise 

the brochure on its Web site that stated some experts believe N-9 may 

prevent HIV and suggested using N-9 along with a condom. Some 

manufacturers we interviewed have also taken steps to inform the public 

about N-9 and HIV, while others have not. (See app. I for a timeline of 

selected events and publications related to N-9’s potential use as a 

microbicide.)
Page 15 GAO-05-399 Nonoxynol-9 and HIV

At Times, CDC and FDA 

Provided Inconsistent 

Information about the Use 

of N-9 to Prevent HIV

In the early 1990s, based on the information that was available at the time, 

CDC cautioned that there was insufficient information to conclude that N-9 

may prevent HIV transmission.34 According to CDC’s 1993 STD treatment 

guidelines,35 “protection of women against HIV infection should not be 

assumed from the use of vaginal spermicides, vaginal sponges, or 

diaphragms.” This document also stated, “No data exist to indicate that 

condoms lubricated with spermicides are more effective than other 

lubricated condoms in protecting against the transmission of HIV 

infection....” This document recommended the use of condoms, with or 

without a spermicide in order to protect against STDs, including HIV.36 

Similarly, an article in a 1993 issue of CDC’s MMWR cautioned that there 

was no evidence that N-9 prevents HIV transmission. According to this 

issue of MMWR, “No reports indicate that nonoxynol-9 used alone without 

condoms is effective for preventing sexual transmission of HIV.” This 

document also repeated the recommendation to use condoms with or 

without a spermicide.37 

By 1998, in response to new research, CDC informed the public that N-9 

should not be used as a microbicide because it does not protect against HIV 

and revised its STD treatment guidelines to state that “vaginal spermicides 

offer no protection against HIV infection, and spermicides are not 

recommended for HIV prevention.” 38 At this time, CDC did not revise its 

recommendation to use condoms with or without spermicide. 

34 Before 1990, CDC published three articles in MMWR stating that based on information 

from laboratory studies, additional protection against HIV and other STDs might be 

obtained from using spermicides in conjunction with condoms. 

35 CDC’s STD treatment guidelines include information for the treatment of patients who 

have STDs. The guidelines were developed after consultation with a group of professionals 

knowledgeable in the field of STDs. These guidelines are periodically updated as new 

information becomes available.

36 Centers for Disease Control and Prevention, “1993 Sexually Transmitted Diseases 

Treatment Guidelines,” Morbidity and Mortality Weekly Report, vol. 42, no. RR-14 

(September 1993).

37 Centers for Disease Control and Prevention, “Update: Barrier Protection Against HIV 

Infection and Other Sexually Transmitted Diseases,” Morbidity and Mortality Weekly 

Report, vol. 42, no. 30 (August 1993).

38 Centers for Disease Control and Prevention, “1998 Guidelines for Treatment of Sexually 

Transmitted Diseases,” Morbidity and Mortality Weekly Report, vol. 47, no. RR-1 (January 

1998).
Page 16 GAO-05-399 Nonoxynol-9 and HIV

FDA’s educational publications during the 1990s also cautioned that N-9 

had not been proven to prevent HIV transmission, but in some cases, the 

agency suggested that N-9, along with a condom, may be used to prevent 

HIV transmission. For example, a 1990 article published in the magazine 

FDA Consumer stated, “Although it has not been scientifically proven, it is 

possible that Nonoxynol-9 may reduce the risk of transmission of the AIDS 

virus during intercourse as well. Using a spermicide along with a latex 

condom is therefore advisable, and is an added precaution in case the 

condom breaks.... Some experts think that even if a condom with 

spermicide is used, additional spermicide in the form of a jelly, cream or 

foam should be added.”39 In 1998, an FDA Consumer article stated that N-9 

may reduce the risk of transmitting certain STDs, but cautioned that it has 

not been proven to prevent sexual transmission of HIV.40 Another 1998 

FDA Consumer article stated that spermicides alone do not give adequate 

protection against HIV.41 However, in 1999, FDA indicated to the public 

that N-9 may protect them against HIV transmission. An FDA brochure 

posted to the Web site and titled Condoms and Sexually Transmitted 

Diseases...Especially AIDS stated, “Some experts believe nonoxynol-9 

may kill the AIDS virus during intercourse, too. So you might want to use a 

spermicide along with a latex condom as an added precaution....”42 

In response to the preliminary results of the COL-1492 study that were 

released at the 2000 International AIDS Conference, CDC revised its earlier 

position on N-9. CDC had previously cautioned that N-9 used alone without 

a condom offered no protection against HIV infection and was not 

recommended for HIV prevention. However, by 2000 CDC’s educational 

publications had included the statement that N-9 may increase the risk of 

transmission when used frequently. In an August 2000 letter to health care 

providers and public health personnel, CDC reported that the preliminary 

results of the COL-1492 study demonstrated that N-9 did not protect against 

39 Food and Drug Administration, “Latex Condoms Lessen Risks of STDs,” FDA Consumer

(1990).

40 Food and Drug Administration, “Condoms: Barriers to Bad News,” FDA Consumer (1998).

41 Food and Drug Administration, “On the Teen Scene: Preventing STDs,” FDA Consumer

(1998).

42 This Web site posting was of a brochure originally issued in 1990. The document stated 

that the information was current as of December 2, 1999. See Food and Drug 

Administration, Condoms and Sexually Transmitted Diseases...Especially AIDS 

(Rockville, Md.: 1990).
Page 17 GAO-05-399 Nonoxynol-9 and HIV

HIV infection and may have caused more transmission. This letter also 

stated that N-9 should not be recommended as an effective means of HIV 

prevention and that the use of N-9 for HIV prevention may be harmful to 

certain users. This warning was also published in an August 2000 issue of 

MMWR.43 Similarly, in 2002 when CDC revised its STD treatment 

guidelines,44 it included information indicating that spermicides containing 

N-9 were not effective in preventing HIV infection and that frequent use had 

been associated with genital lesions, which may be associated with an 

increased risk of HIV transmission. These revised STD treatment 

guidelines further stated that condoms lubricated with spermicides are no 

more effective than other lubricated condoms in preventing HIV 

transmission, and also stated that “purchase of any additional condoms 

lubricated with the spermicide N-9 is not recommended.”45 This 

information also appeared in an article in a May 2002 issue of MMWR.46

43 Centers for Disease Control and Prevention, “Notice to Readers: CDC Statement on Study 

Results of Product Containing Nonoxynol-9,” Morbidity and Mortality Weekly Report, vol. 

49, no. 31 (August 2000).

44 Since 1990, CDC has revised it STD treatment guidelines three times—in 1993, 1998, and 

2002.

45 Centers for Disease Control and Prevention, “Sexually Transmitted Diseases Treatment 

Guidelines 2002,” Morbidity and Mortality Weekly Report, vol. 51, no. RR-6 (May 2002).

46 Centers for Disease Control and Prevention, “Nonoxynol-9 Spermicide Contraception 

Use – United States, 1999,” Morbidity and Mortality Weekly Report, vol. 51, no. 18 (May 

2002).
Page 18 GAO-05-399 Nonoxynol-9 and HIV

While CDC was informing the public that N-9 was not effective in 

preventing HIV and that frequent use of N-9 may increase the risk of HIV 

transmission, the public would have obtained different information from 

FDA. An FDA official told us that the agency has not disseminated any new 

educational materials related to N-9 and HIV transmission since 2000. 

However, FDA left its brochurewhich stated that some experts believe 

that N-9 may prevent HIV transmissionon its Web site until this 

information was deleted in September 2003 when FDA officials realized the 

information in the brochure on the Web site was inconsistent with the 

proposed warning labels for N-9 vaginal contraceptive products.47 

According to one FDA official, documents on the agency’s Web site were 

updated in an “ad hoc” manner, rather than through an official process.48

Some Manufacturers Have 

Taken Steps to Inform 

Consumers about N-9 and 

HIV

The three largest condom manufacturers have taken steps to inform the 

public about N-9 and HIV. In particular, one condom manufacturer has 

taken multiple steps to inform its consumers that N-9 does not prevent HIV 

transmission and may increase some users’ risk of contracting HIV. This 

large manufacturer of condoms has added warning labels to N-9 condom 

packaging that indicate that N-9 is not effective in protecting against HIV. 

This manufacturer has also published pamphlets and used similar language 

on its Web site to explain to consumers the risks associated with N-9. In 

addition, two other large manufacturers of condoms added warnings to 

their Web sites about the use of N-9. In contrast, officials from major 

manufacturers of vaginal contraceptive products that we interviewed told 

us they have not disseminated such information. One of these 

manufacturers reported that its review of research on N-9 suggested that 

the link between the use of N-9 and an increased risk of HIV infection was 

speculation.

47 In January 2003, FDA proposed adding warning labels that indicate that vaginal 

contraceptive products with N-9 do not protect against HIV or other STDs and that frequent 

use, such as more than once a day, of N-9 can increase vaginal irritation, which may increase 

the risk of contracting HIV from infected partners. 

48 An official from FDA’s Office of Public Affairs stated that the office is responsible for 

updating information available on the FDA Web site. 
Page 19 GAO-05-399 Nonoxynol-9 and HIV

Some Manufacturers 

and Public Health 

Organizations Have 

Stopped Producing and 

Distributing N-9 

Condoms

In recent years, there have been several changes in the production, 

distribution, and promotion of N-9 condoms. In January 2004, the condom 

manufacturer SSL International announced that it was halting production 

of its Durex brand condoms that are lubricated with N-9 because of a 

decrease in sales to public health agencies and because of an anticipated 

decrease in retail sales. SSL International representatives attributed this 

decrease in sales to safety concerns raised by the 2002 release of the 

WHO/CONRAD report. Another large manufacturer of condoms reported 

that the percentage of N-9 condoms sold on the retail market declined from 

2000 to 2003.

Like SSL International, PPFA and a leading distributor—Mayer 

Laboratories—have also stopped manufacturing and distributing N-9 

condoms. A representative from PPFA told us that the organization 

stopped manufacturing N-9 condoms in June 2002 because of safety 

concerns based on published scientific studies indicating that N-9 does not 

protect against HIV and that frequent N-9 use may actually increase HIV 

transmission. In addition, a representative from PPFA stated that its 

decision to halt production of N-9 condoms was influenced by the release 

of the conclusions of the WHO/CONRAD report and the outcome of a 

meeting with public health entities organized by the Global Campaign for 

Microbicides.49 Another public health organization, the Gay Men’s Health 

Clinic in New York, has also begun to recommend that clients not use N-9 

condoms. As of early in 2003, a distributor—Mayer Laboratories—stopped 

distributing N-9 condoms. Information from Mayer Laboratories stated 

that this decision was based on a concern about the safety of N-9 condoms. 

Concluding 

Observations

CDC’s and NIH’s efforts to research N-9’s potential use as a microbicide 

ended in 2000, when the preliminary results of a major clinical trial 

indicated that N-9 may actually increase the risk of contracting HIV. CDC 

has warned that N-9 may increase the risk of HIV transmission when used 

frequently, and some manufacturers of N-9 condoms have taken steps to 

either add their own warning labels or remove their N-9 condoms from the 

market, while other manufacturers have not taken such steps. FDA has 

proposed requiring new warning labels that indicate that N-9 vaginal 

49 The Global Campaign for Microbicides is an organization that works to accelerate 

microbicide development, facilitate widespread access and use, and protect the needs and 

interests of users through advocacy, policy analysis, and social science research.
Page 20 GAO-05-399 Nonoxynol-9 and HIV

contraceptive products do not protect against HIV or other STDs and that 

frequent use, such as more than once a day, may increase the risk of 

contracting HIV. FDA is also developing proposed warning labels for N-9 

condoms. While FDA expects to issue the final rule for the new warning 

labels for vaginal contraceptive products by September 2005, it has not yet 

issued proposed warning labels for N-9 condoms, and it has not indicated a 

target date to issue the final warning labels for N-9 condoms. Since FDA is 

still in the process of completing warning label changes for N-9 vaginal 

contraceptive products and condoms, the public may be left in doubt about 

the appropriate uses of these products until FDA finalizes these warnings. 

Further, the public may be at risk if the products are used inappropriately.

Agency Comments HHS provided written comments on a draft of this report. (See app. II).

In its written comments, HHS stated that the final sentence in the draft 

report—that said the public may be at risk until FDA finalizes the warning 

labels for N-9 vaginal contraceptive products and N-9 condoms—may 

unintentionally undermine efforts to inform the public of the protection 

provided by condoms. HHS suggested we modify this to say that 

consumers may be left in doubt about the appropriate uses of these 

products. We have revised the conclusion to acknowledge that until FDA 

finalizes its warning labels, consumers may be left in doubt about the 

appropriate uses of these products. However, the conclusion also states 

that the public may be at risk if the products are used inappropriately. 

In its written comments, HHS stated that the draft did not indicate that 

FDA had never permitted condom labeling to claim that N-9 provides any 

additional protection against HIV or other STDs. To ensure clarity on this 

issue, we have added this statement to the report. HHS’s written comments 

also stated that it is important to make clear that the barrier features of 

condoms provide the primary protection against STDs and the primary 

contraceptive protection. While this is an important fact in educating 

consumers about methods to protect themselves against STDs, the 

objectives of this report were focused on N-9 and its potential as a 

microbicide. 

HHS’s written comments also stated that FDA’s primary means of public 

health communication is through product labeling oversight and that FDA 

has, on occasion, provided supplementary information through consumer 

outreach efforts. The draft report noted the role FDA has in labeling 

oversight and described FDA’s proposed warning labels for N-9 vaginal 
Page 21 GAO-05-399 Nonoxynol-9 and HIV

contraceptive products and its efforts to develop proposed warning labels 

for N-9 condoms. The draft report also described the information FDA 

provided to the public through a brochure that it posted to its Web site and 

through FDA Consumer magazine articles. HHS’s written comments also 

stated that the supplementary statements FDA provided to the public 

through consumer outreach efforts always acknowledged the scientific 

uncertainty concerning the effectiveness of N-9 as a protection against 

STDs. Examples of FDA’s acknowledgement of scientific uncertainty were 

provided in the draft report. 

HHS also commented that the timeline in appendix I should begin with the 

1988 CDC brochure Understanding AIDS, which advised that N-9, when 

used with a condom, might provide additional protection against HIV. We 

mentioned this brochure in the introduction to the draft report when we 

stated that in the mid-1980s N-9 showed promise as a potential microbicide 

for STDs, including HIV. However, as we stated in the scope and 

methodology section of the draft report, we focused our review on efforts 

to research and provide public information on N-9 and HIV from 1990 to the 

present because concerns about the safety of N-9 in preventing HIV first 

began to surface in about 1990. Further, HHS commented that the timeline 

should make clear that the first indication that N-9 presented added risks 

did not emerge until 2000 (the COL-1492 study). However, this study was 

not the first indication that N-9 presented added risks, and the draft report 

discussed earlier concerns.

HHS’s written comments also made a number of other suggestions to 

clarify the draft report, which we incorporated. First, HHS suggested that 

we clearly indicate in the report when we are discussing vaginal 

contraceptive products containing N-9, condoms with N-9, or both. We 

have reviewed the report for clarity and made changes where necessary. 

Second, HHS’s comments stated that much of the research discussed in the 

report was restricted to vaginal contraceptive products and that these 

studies did not involve N-9 condoms. We have clarified this point in the 

report. Finally, HHS’s comments stated that the 1999 FDA brochure 

Condoms and Sexually Transmitted Diseases . . . Especially AIDS was an 

Internet posting of a brochure initially issued in 1990. We clarified the text 

of our report to note that the Web site posting was of a brochure originally 

issued in 1990 and that the document stated the information was current as 

of December 2, 1999. We also added the 1990 brochure to the timeline in 

appendix I. 
Page 22 GAO-05-399 Nonoxynol-9 and HIV

HHS included several other comments. First, HHS stated that we should be 

clear that N-9 condoms are regulated as medical devices not through the 

monograph process. This information was discussed in the background 

section of the draft report. Second, HHS’s written comments stated that 

the report should recognize that some manufacturers stopped selling 

condoms with N-9 because of economic considerations and not safety 

concerns. This information was included in the draft report and we noted 

further that one manufacturer attributed the decrease in sales of N-9 

condoms to the safety concerns raised by the 2002 release of the 

WHO/CONDRAD report. Third, HHS raised concerns that the draft report 

had not explained the significance of the actions of manufacturers. This 

information was included in the draft report. Finally, HHS’s comments said 

we should note that the report on the COL-1492 study was published in 

2002 and the information available prior to that time could be considered 

only preliminary. This information was also reflected in the draft report 

and in the timeline in appendix I.

HHS’s comments are reprinted in appendix II. HHS also provided technical 

comments, which we incorporated into the report as appropriate.

As we agreed with your offices, unless you publicly announce the contents 

of this report earlier, we plan no further distribution of it until 30 days from 

its date. We will then send copies to others who are interested and make 

copies available to others who request them. In addition, this report will be 

available at no charge on GAO’s Web site at http://www.gao.gov.

If you or your staff have any questions about this report, please call me at 

(202) 512-7114. Another contact and key contributors are listed in 

appendix III.

Marjorie Kanof

Managing Director, Health Care
Page 23 GAO-05-399 Nonoxynol-9 and HIV

Appendix I

Timeline of Selected Events and Publications Apendxies

Related to N-9’s Potential Use as a 

Microbicide, 1990–2004 ApendxiI

1990: An FDA brochure, Condoms and STDs. . . 

Especially AIDS, stated that “Some experts 

believe nonoxynol-9 may kill the AIDS virus 

during intercourse, too. So you might want to use 

a spermicide along with a latex condom as an 

added precaution. . . .”

1990: An FDA Consumer magazine article, “Latex 

Condoms Lessen the Risk of STDs,” stated that 

“Although it has not been scientifically proven, it 

is possible that nonoxynol-9 may reduce the risk 

of transmission of the AIDS virus during 

intercourse. . . .”

1993: “CDC Update: Barrier Protection Against 

HIV Infection and Other Sexually Transmitted 

Diseases” in MMWR stated that “No reports 

indicate that nonoxynol-9 used alone without 

condoms is effective for preventing sexual 

transmission of HIV.. . . No data exist to indicate 

that condoms lubricated with spermicides are 

more effective than other lubricated condoms in 

protecting against the transmission of HIV 

infection.... Therefore, latex condoms with or 

without spermicides are recommended.”

1993: CDC’s 1993 STD treatment guidelines 

stated that “protection of women against HIV 

infection should not be assumed from the use 

of vaginal spermicides, vaginal sponges, or 

diaphragms.”

1997: CDC publication What We Know About 

Nonoxynol-9 for HIV and STD Prevention stated 

that “CDC does not recommend using 

spermicide alone to prevent HIV infection.”

1998: CDC’s 1998 STD treatment guidelines 

stated that “vaginal spermicides offer no 

protection against HIV infection, and spermicides 

are not recommended for HIV prevention . . . the 

consistent use of condoms, with or without 

spermicidal lubricant or vaginal application of 

spermicide is recommended.”

1998: An FDA Consumer magazine article, 

“Condoms: Barriers to Bad News,” stated that 

“The spermicide nonoxynol-9, used in some 

condoms, has been shown to be effective as a 

contraceptive, and may reduce the risk of 

transmitting certain STDs. But the spermicide 

has not been proven to prevent sexual 

transmission of HIV.”

1998: An FDA Consumer magazine article, “On 

the Teen Scene: Preventing STDs,” stated that 

“... spermicides alone ... do not give adequate 

protection against HIV and other STDs.”

1999: An FDA brochure on its Web site and 

titled Condoms and STDs... Especially AIDS

continued to include the statement “Some 

experts believe nonoxynol-9 may kill the AIDS 

virus during intercourse, too. So you might want 

to use a spermicide along with a latex condom 

as an added precaution....”

2000: Preliminary results of a major clinical study 

among high-risk female sex workers were 

presented at the International AIDS conference 

in Durban, South Africa. The results indicate that 

N-9 is not effective as a microbicide against HIV 

and may increase certain users’ risk of 

contracting the virus.

2000: NIH and CDC reported that the agencies 

halted all studies actively pursuing N-9’s use as 

a microbicide between 2000 and 2001.

2000: A CDC letter issued to health care 

providers and public health personnel stated that 

because N-9 has been shown to be ineffective 

against HIV and may increase HIV risk among 

certain user groups, N-9 should not be 

recommended for HIV prevention.

2001: WHO, in collaboration with CONRAD, 

convened a meeting to review the available 

literature regarding N-9’s safety and effectiveness as a spermicide and a microbicide.

2002: The final results of the presentation at the 

International AIDS conference held in Durban, 

South Africa, were published in The Lancet.

2002: CDC published a report in MMWR stating, 

“Sexually active women should consider their 

individual HIV/STD infection risk when choosing 

a method of contraception. Providers of family 

planning services should inform women at risk 

for HIV/STDs that N-9 contraceptives do not 

protect against these infections.”

2002: CDC’s 2002 STD treatment guidelines 

stated that “Recent evidence has indicated that 

vaginal spermicides containing nonoxynol-9 (N9) are not effective in preventing . . . HIV infection. 

Thus, spermicides alone are not recommended 

for STD/HIV prevention. Frequent use of spermicides containing N-9 . . . may be associated with 

an increased risk of HIV transmission . . . . 

Purchase of any additional condoms lubricated 

with the spermicide N-9 is not recommended. . . .”

2002: WHO and CONRAD published the 

summary report of their consultation on the 

available literature regarding N-9’s safety and 

effectiveness as a spermicide and a microbicide.

2002: PPFA halted production and distribution 

of N-9 condoms.

2003: Mayer Laboratories halted distribution of 

N-9 condoms.

2003: FDA proposed warning labels for vaginal 

contraceptive drug product packaging. The 

proposed warning stated that vaginal contraceptive products with N-9 do not protect against 

HIV or other STDs and that frequent use of 

N-9 can increase vaginal irritation, which may 

increase the risk of contracting HIV or other 

STDs. The warnings also indicated that the 

labeled products were for vaginal use only.

2004: SSL International halted production of its 

Durex brand condoms that were lubricated with 

N-9 because of a decrease in sales to public 

health outlets and a projected decrease in 

retail sales. 

1990s1990s 2000s2000s

▼ ▼

Source: GAO.
Page 24 GAO-05-399 Nonoxynol-9 and HIV

Appendix II

Comments from the Department of Health and 

Human Services ApendxiI
Appendix II

Comments from the Department of Health 

and Human Services

Page 25 GAO-05-399 Nonoxynol-9 and HIV
Appendix II

Comments from the Department of Health 

and Human Services

Page 26 GAO-05-399 Nonoxynol-9 and HIV
Appendix II

Comments from the Department of Health 

and Human Services

Page 27 GAO-05-399 Nonoxynol-9 and HIV
Page 28 GAO-05-399 Nonoxynol-9 and HIV

Appendix III

GAO Contact and Staff Acknowledgments ApendxiI

GAO Contact Kristi A. Peterson, (202) 512-7951

Acknowledgments In addition to the person named above, Kelly DeMots, Krister Friday, Mary 

Giffin, and Mary Reich made key contributions to this report.

(290314)
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