Analysis Human Rights

From Tuskegee to Transparency: An Evolution in the Ethics and Accountability of Clinical Trials Involving Human Subjects

Kate Ryan & Anna Forbes

People who participate in clinical trials take the enormous step of volunteering to test a product that may be useful and, sometimes, life-saving if it turns out to be effective. They play an irreplaceable role in research to prevent, treat, and sometimes cure illness – as well as to find other ways to improve people’s health and lives.

An error in this article was corrected at 1:07 p.m. on Friday, November 4th, 2011. The article originally incorrectly stated that the Tuskegee Study was conducted in Mississippi, but was conducted in Alabama.

People who participate in clinical trials take the enormous step of volunteering to test a product that may be useful and, sometimes, life-saving if it turns out to be effective. They play an irreplaceable role in research to prevent, treat, and sometimes cure illness – as well as to find other ways to improve people’s health and lives.

Trial participants make a profoundly personal contribution and accept potential medical, social, and personal risks on behalf of others. An ethical trial is one that eliminates or minimizes participants’ risks as much as possible, invests in making sure that participants understand clearly what they are volunteering for, and protects their rights at every step.

For example, without clinical trials, we would not have seen recent advances in antiretroviral drugs to treat HIV, long-acting contraceptive choices that allow women greater control over their use, or microbicides that may be able to protect women from HIV.

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The United States government has rules to protect people who participate in federally-funded biomedical and behavioral research. The rules vary depending on which agency is supporting the research, but they all share a starting point known as the Common Rule, a set of regulations for all federally-funded research involving human participants, whether it is conducted inside or outside the U.S.

But those rules have not always been in place, and there are some shameful chapters in the history of medical research supported by the United States that include violations of the most basic standards of ethical behavior.  This history has left some people deeply suspicious of clinical trials and the motives of those who conduct them. Many explain their suspicion with one word: “Tuskegee.”

Conducted in Alabama between 1932 and 1972 by white researchers, the Tuskegee syphilis study enrolled African American farmers with syphilis, many of who could not read. The researchers told them that they would receive treatment for “bad blood” (a general expression people used to cover a range of conditions from anemia to sexually transmitted infections). What the researchers actually did, however, was observe what happened in the men’s bodies as their untreated syphilis progressed.

In 1947, penicillin was recognized as the best treatment for syphilis but the researchers did not relay this news to the trial participants. Instead, they continued the trial and deliberately kept participants from receiving treatment. Advocates finally succeeded in stopping the trial 25 years later by capturing media attention, and a subsequent Congressional advisory panel concluded that the Tuskegee Study was “ethically unjustified.” The advocates then filed a class-action lawsuit on behalf of the study participants and their families. In 1974, a $10 million out-of-court settlement was reached that ultimately required the U.S. government to provide lifetime medical and health benefits and burial services to all living participants of the trial, as well as their wives, widows and offspring.

To prevent future abuses, Congress passed the National Research Act in 1974, creating the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research.  The Commission developed a set of basic principles outlining what constituted ethical medical research and the regulations created to enforce these, in turn, became known as the Common Rule.  By 1991, the U.S. Department of Health and Human Services (DHHS) and 14 other federal agencies had adopted the Common Rule.

The protections now required seem so obvious that it is hard to believe that they were not uniformly applied until 30 years ago.  Two examples of protections established following the Tuskegee abuse are:

Institutional Review Boards (IRBs) which review and approve a clinical trial’s protocol (describing every step to be taken in the trial) before it can begin. They are made up of researchers, usually at least one lawyer and one ethics expert, and a few people who are knowledgeable about the communities from which trial participants will be recruited. In the US, the medical institutions and universities engaged in research set up these Boards. At least one Board member on each IRB, however, must be someone who does not work for the institution whose trials are being reviewed. These boards are called Research Ethics Committees [RECs] in most other countries.

Informed Consent: Participants must give their voluntary informed consent before they can participate in a study. To do this, they must show that they understand what the trial is designed to do and how it works. Every step of the trial has to be explained in the language the participant is most comfortable using. Pictures and flip charts can be used to help participants who do not read well. This information must be provided multiple times, in conversations that happen on separate days.  This gives people time to think about what they have heard and talk with friends or family before deciding whether to volunteer. Trial counselors must also review the informed consent information periodically with participants when they come in for check ups, reminding them that they have the rights to privacy, full confidentiality and to drop out of the study at any time without giving a reason, if they wish to do so.

But while the regulations created in the wake of Tuskegee were a vitally important step forward for medical research ethics, the landscape of research and clinical trials has changed since 1991 and the Common Rule is overdue for an update. The number of trials being conducted has expanded enormously, creating a greater workload for IRBs. The nature of the research has also changed in some important ways.  In 1991, most U.S.-funded trials took place at a single site (in one city or at one research institution). Now, many trials have multiple sites throughout the United States and, increasingly, around the world. Total public and private spending on health-related research has tripled since 1990, feeding the emergence of an industrial sector comprised of businesses that specialize in the recruitment of research participants, coordination of multi-site trials, and data analysis, as well as for-profit Contract Research Organizations (CROs) that will conduct drug company trials from beginning to end. 

Ensuring participants’ privacy rights is more complex now than when the Common Rule was drafted. Today, rules are needed to protect records and databases that are managed and stored electronically and that contain more detailed information, including genetic data, than could be collected in 1991.  Consent forms have also become increasingly long and legalistic making it all the more challenging to render them fully comprehensible to people with no medical or legal training.

Advocacy pressure has developed to update the Common Rule regulations to deal with these current realities, and DHHS has proposed several revisions that would modernize it.  These updates would mandate data security standards, designate lead-IRBs for multi-site clinical trials so that individual IRBs don’t have to duplicate work, and prescribe the appropriate content, length, format, and literacy level for consent forms – to make sure that they are as understandable as possible to trial participants. 

DHHS posted its proposed revisions to the Common Rule for public review and comment in July of this year. Civil society, research and corporate entities were invited to submit comments by October 26, and hundreds of groups responded, ranging from women’s advocacy groups such as the National Women’s Health Network, the National Research Center for Women and Families, and Breast Cancer Action to Stanford University to drug companies such as Pfizer to the National Association of Children’s Hospitals.

This process provided the opportunity for advocates and others to consider and articulate the progress that has been made in our understanding of clinical trial ethics, and what additional improvements need to be made.

When considering improvements to protections for people participating in research, there is much to be learned from the work of women’s health advocates, many of them based in Africa, who have been actively involved in reviewing clinical trial ethics and advocating for change during this 30 year span. Nowhere is this more evident than in clinical trials of HIV treatment and prevention methods. Gaps remain, but there have been significant advances in research practices, especially regarding treatment of women participants, thanks to work done by the Gender AIDS Forum, the Treatment Action Campaign, the International Coalition of Women Living with HIV/AIDS, the Global Campaign for Microbicides (GCM) and others.

Sexual and reproductive health needs of women trial participants 

The most progress in addressing the sexual and reproductive health needs of trial participants has been made among research entities testing microbicides because the provision of counseling and safe, appropriate contraception to women enrolling in microbicide trials has been shown to help with participant recruitment and retention. Microbicides are products designed to be inserted vaginally or rectally to reduce the risk of HIV transmission if a condom is not being used during sex.

Not only does women’s desire for these services encourage them to join a trial, but access to acceptable and effective contraception helps to reduce the number of participants dropping out of trials due to unintended pregnancy. Advocates have pressed for a woman-responsive approach to care and services provided at microbicide trial sites that would include:

  • Free access to a range of non-condom contraceptive options and counseling on their various advantages and disadvantages, in addition to risk reduction counseling that stresses the importance of male and female condoms for HIV prevention;
  • Access by supported referral to pregnancy care for participants who conceive;
  • Access by supported referral to safe abortion, when requested, or to safe post-abortion care in countries where legal abortion is inaccessible;
  • Screening for cervical cancer and access to care for cervical dysplasia;
  • Counselors competent to handle gender-based violence issues and prepared to link participants with psychosocial services as needed.

A 2008 survey conducted by the GCM indicated that, out of six of the trial sites visited in four African countries, all provided male condoms, most provided female condoms, most provided contraception on site (although a few referred women to other providers for it), and provided pregnancy testing and referrals for ante-natal care.  None, however, provided emergency contraception or full information accessing pregnancy termination, the risks of unsafe abortion, or access to post-abortion care.   

On-going care for people who become HIV positive during an HIV prevention trial 

In 2004 and 2005, two HIV prevention trials were halted by government order in both Cambodia and Cameroon because of controversy over several issues, chief among them the fact that the research sponsors had not made a commitment to ensuring participants would receive on-going anti-retroviral treatment (ART) if they acquired HIV during the trial. 

As a result of this upheaval and cancellation of the trails, a political consensus has emerged that trial participants have a right to on-going access to treatment if they become HIV positive during the trial. Trial sponsors and governments still struggle with the logistics of implementing this commitment but the question of whether publicly-funded HIV prevention trials will take steps to assure it is no longer debated.

Earlier implementation of Data Safety Monitoring Boards (DSMBs)

A DSMB is a board of independent experts (not involved in running the trial) that carefully examines the trial data while the trial is going on. No research staff can look at the data until the trial is completed. But the external DSMB does “spot checks” so a trial can potentially be stopped if it looks as though:

1. the test product is definitely effective;

2. the test product may be causing harm;

3. the trial can no longer answer the original questions it was designed to answer.

A microbicide trial of a candidate product called Cellulose Sulfate, for example, was stopped when the DSMB saw data suggesting the use of the product might slightly increase women’s risk of contracting HIV.  

The Women’s Health Initiative – a research program evaluating long-term use of hormone therapy – had to stop one of its trials when the DSMB saw data showing that women taking the hormone pills had an increased risk of heart disease and breast cancer compared to women taking the placebo, or sugar, pills.

The National Institutes of Health in the US and the Medical Research Council in the UK first used DSMBs in the 1960s.  At that time, however, they were not generally convened until after the trial was already well underway. In 1988[1], advocates began to call for the establishment of DSMBs before the start of a trial, to help assure maximum safety.

Maintaining and building on the gains

These gains must be monitored and reinforced so that they do not slip away as economic pressures on research institutions lead them to scale back trial budgets.  And there are gaps that remain to be addressed. Some of these gaps have been filled in the following ways.

Expanding community involvement and consultation and the development of community advisory boards (CABs)

Over the last two decades, HIV-focused researchers have come to realize that involving people from the communities where they are conducting clinical trials is not only the right thing to do but also smart.  After seeing trials become embroiled in controversy and even closed when they lacked community support, most HIV prevention trials have adopted practices to ensure that that these stakeholders have regular opportunities to give input and to learn about how the trial works and how it is progressing.  They hire community liaisons as part of their trial staff, hold community consultations and convene on-going community advisory boards (CABS). 

Doing this successfully requires that researchers invest in building “research literacy” among interested community members, to help people with no science training and, often, little formal education clearly understand what the trial is doing and why it operates as it does.  This understanding enables community members to provide well-informed recommendations and levels the playing field for meaningful discussions and debates about aspects of the trials that stakeholders may feel should be changed.

Unfortunately, this investment in full and robust community involvement –and in the staff who make it happen – are among the first things to go when research funding is reduced.  Advocates now face the challenge of building enough political support for community involvement programs to protect them from staff and funding cut-backs.

Providing the best available prevention package

Currently, HIV prevention trials routinely provide participants with condoms (although not all trials provide female as well as male condoms).  They also provide STI diagnosis and treatment and risk reduction counseling in the participant’s language.

In 2007, UNAIDS issued guidance that included language specifying that trial participants should receive counseling and access to all “state-of-the-art” HIV risk reduction. There is ongoing debate, however, about how state of the art is defined.  Some trials offer circumcision to uncircumcised male participants, and some people argue that it should be offered in all trials.  Advocates have also argued that gender-based violence and substance abuse (including alcohol) are factors demonstrably associated with heightened HIV risk and that, therefore, services to address these should also be available to all HIV prevention trial participants.  In 2005, an HIV vaccine trial called AIDSVAX declined to provide 1600 injection drug using participants with clean injecting equipment, despite strong evidence that doing so would reduce their HIV risk. 

Conclusions

The landscape of research and clinical trials has changed dramatically since 1991, not only in technical ways, but also – at least in HIV prevention research — in terms of how research entities relate to trial participants and communities where they are working. 

Advances in ethical reasoning, community and international pressure, and sometimes sheer pragmatism, have changed research norms for that field.  As a result, clinical trial participation is now less risky, fairer and more beneficial to trial participants. 

The updating of the Common Rule offered advocates an opportunity and a challenge – a chance to get the new practices codified to the greatest extent possible, protecting them against roll backs in the current climate of economic cut-backs and extending them to other areas of research.  In addition to the ethical arguments that advocates have been making, it is important to emphasize that where these practices have been adopted:

  • Trials are less likely to be shut down due to community opposition,
  • Trial participants are more likely to be candid with researchers about their use of the test product, preferences, and behaviors (thus generating more accurate data), and
  • Communities may be more inclined to host, and benefit from, future trials. 

Thus, their adoption is both the ethical and the smart thing to do. More and better tools to protect women’s sexual and reproductive health cannot be developed without ongoing clinical research. Even the best researchers cannot conduct effective trials without community support and motivated participants who adhere to trial protocols. Such individual and collective participation is generated by trials that actively display their commitment to doing ethical research that respects and benefits trial communities, as well as the wider world. 


[1] “Data Monitoring in Clinical Trials A Case Studies Approach”, by DeMets, Furberg, and Friedman; published by Springer, 2006

Commentary Health Systems

The FDA Needs an Action Plan for More Inclusive Clinical Trials

Cindy Pearson & Susan Wood

If not enough women and people of color are included in clinical trials, it is not possible to determine how they’re affected by the new drug or device. And without this information women, particularly women of color, can’t make informed decisions about the medical products available.

More than 23 years ago, we met each other for the first time. Susan was a science advisor to the Congressional Caucus on Women’s Issues and Cindy was program director of one of the largest women’s health consumer group, the National Women’s Health Network. We were both upset about how little research was being done on women’s health issues, and together with many important allies and several determined female members of Congress, we worked to change the law to ensure that women’s health research could no longer be ignored.

We’re proud of what’s been accomplished since the National Institutes of Health Revitalization Act went into effect in 1993. Women and people of color are more likely to be included in clinical trials than they used to be.

Women’s health issues are no longer ignored, and we know a lot more about conditions like endometriosis, fibroids, interstitial cystitis, lupus, and TMJ than we used to. We also know a lot more about the natural course of menopause, how aging affects women, and how heart disease is and isn’t the same in males and females.

But, there are some important things we still don’t know about women’s health. All too often, we do not know how drugs and medical devices affect women and people of color. How can we not know the effect of medications and medical devices on women? Because, until now, the Food and Drug Administration (FDA) has only recommended, not required, pharmaceutical companies to look at women separately from men. We have more studies on women’s health conditions, and we have more women and people of color in studies, but we don’t have nearly enough information on how women fare, compared to men; nor do we know enough about how people of color fare.

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Because women are less likely than men to be included in clinical trials, we often don’t discover if a drug or device is unsafe or less effective for women until after it is on the market being used by thousands of women, as was the case with Ambien (a sleeping medication). It was recently discovered that the FDA-approved dose of Ambien was too high for women—twice as high. The double dose made women more likely to be drowsy the next morning, putting them at risk of a car accident and other serious harms. But this is not just about a single drug: A 2001 study showed that eight in ten drugs recalled from the market posed a greater health risk to women than to men. The problem persists to this day, as many important studies still don’t include enough women or people of color. For example:

  • Only one-third of patients in clinical trials studying heart disease are women, despite the fact that heart disease is the leading cause of death for women in the United States. African-American women specifically are 40 percent more likely to die of heart disease than white women, according to the American Heart Association.
  • Two-thirds of people with Alzheimer’s disease are women, but most studies of Alzheimer’s disease have not been designed to evaluate differences based on sex or ethnicity. Among participants in four National Institute on Aging–funded Alzheimer’s Disease Cooperative Study trials, only about 6 percent of participants were African American and roughly 4 percent were Hispanic.
  • More women die of lung cancer each year than from breast, ovarian, and uterine cancers combined, yet women—particularly racial and ethnic minorities—are still less likely to be in these trials than white men and the data is unlikely to be analyzed for sex, race, or ethnic differences. According to data released at an international conference on lung cancer, 58 percent of lung cancer patients in the United States are men and 42 percent are women; however, only 32 percent of lung cancer trial patients were women. Moreover, African Americans develop lung cancer at a higher rate than Caucasians, but this group represented only 2 percent or fewer of lung cancer trial participants.

If not enough women and people of color are included in the studies, it is not possible to determine how they’re affected by the new drug or device. And without this information women, particularly women of color, can’t make informed decisions about the medical products available.

So, 23 years later, we are still working to make change. In 2012, we partnered with allies, including WomenHeart, the Society for Women’s Health Research, and the American Heart Association, along with the National Women’s Health Network, and successfully pressed Congress to pass legislation directing the FDA to ensure that companies seeking its approval include women and minorities in clinical trials, evaluate the safety and effectiveness data by sex, race, and ethnicity, and make this information (or lack of information) publicly available.

Last summer, the FDA released a report evaluating how well women and minorities are included in clinical trials and whether the data is analyzed for differences in safety or effectiveness based on sex, race, and ethnicity. Unfortunately, the report showed that the research submitted to the FDA still is not adequate when it comes to evaluating sex and gender differences or differences due to race and ethnicity. Even though women and people of color are included in trials, they aren’t being included in sufficient numbers to actually get good information.

Thankfully, this report is not the end of the line. In August, the FDA is due to release an action plan to improve the data it gets about medical products for women and communities of color. We are urging the agency to take this opportunity to develop and implement an action plan that truly addresses the deficiencies revealed by its report and meets the needs of women and communities of color. Specifically, we urge the FDA to address the lack of evidence on sex, race, and ethnicity-specific effects of drugs and medical devices, including the following requirements in its action plan:

  1. Companies must not only include women and minorities in clinical trials submitted to the FDA, but ensure there are enough people in the trial to analyze it based on sex and on race and ethnicity.
  2. Companies and the FDA must use this information to evaluate the safety and effectiveness of drugs and devices based on sex, race, and ethnicity.
  3. Information on sex, race, and ethnicity-specific safety and effectiveness must be made publicly available and included on the labels of drugs and devices.
  4. The FDA must reject applications that do not include sufficient information about women and people of color.

The FDA has an important opportunity to improve public health by requiring companies to do the right thing. We will continue to push the agency to release a strong action plan, and we ask you to join us in urging the agency to stand strong and ensure that new drugs and devices are only approved when critical data on sex differences are available, so that women and health-care providers can make informed decisions about their health care.

Analysis Sexual Health

What’s Up With Women and HIV-Prevention Method PrEP?

Anna Forbes

PrEP works when used properly. So why don't women use it?

At the 20th Conference on Retroviruses and Opportunistic Infections (CROI) in Atlanta this week, researchers reported that, in a large scale trial among African women, neither oral pre-exposure prophylaxis (PrEP) nor the daily use of vaginal gel containing an anti-retroviral (ARV) drug had shown effectiveness in reducing HIV risk.

The clinical trial, Vaginal and Oral Interventions to Control the Epidemic (VOICE), enrolled 5,029 HIV-negative women and randomized them into five study arms. In one group, women were asked to take an oral tenofovir (an ARV tablet) daily. In a second arm, women tested the daily use of oral TDF/FTC (a two-ARV combination called Truvada), and in the third, women were asked to insert a vaginal gel containing 1 percent tenofovir gel that had been shown in a previous study to provide moderate protection against HIV.

The fourth and fifth arms were placebo controlled; women received either a pill or a gel that looked identical to the study products but contained no active ingredients. Comparing the rate of new HIV infections occurring among women in the control arms with those of women in the various intervention arms allowed the researchers to see if the use of the interventions reduced women’s rate of HIV acquisition. Participants in all arms were also regularly provided with free condoms, counseling about the need to use condoms consistently, and testing and treatment for sexually-transmitted infections (STIs) to reduce their HIV risk to the greatest extent possible.

Despite the fact that other trials of oral PrEP have shown some effectiveness in women, none of the VOICE interventions resulted in decreased HIV acquisition rates. Dr. Jeanne Marrazzo, co-principle investigator for the VOICE study, reported in her presentation at CROI that it appears relatively few participants in intervention arms of the trial actually used the products daily as instructed. By testing blood samples for the presence of the ARVs in the body, the researchers saw that only 25 to 30 percent of the women were using the products as instructed. A similar lack of adherence to daily product use also led to discontinuation of the FEM-PrEP trial in 2011.

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The VOICE results are particularly frustrating and sad because of the high rates of new HIV infection that occurred among women in the trial. Even with the benefits of medical care, free condoms, condom counseling, and more, the rates were high—6.3 percent among women in the oral tenofovir arm, 4.2 percent in the placebo oral arm, 4.7 percent in the Truvada arm, 5.9 percent in the tenofovir gel arm, and 6.8 percent in the placebo gel arm. The researchers reported that the greatest number of new infections occurred among women who were under the age of 25 and unmarried. The rate of women becoming HIV positive was less (although still high) among women who were over the age of 25, married, and/or who had partners over the age of 28. This pattern is prevalent globally. Even in the United States, younger women are at greater risk of HIV than their older cohorts.

This is also frustrating because we know that PrEP works when people use it. Data demonstrating this led to the Food and Drug Administration’s approval of Truvada for HIV prevention in the United States last year. In a 2010 study called iPrEx, Truvada reduced HIV risk among men and transgender women who have sex with men by 44 percent. Data from this study suggested that participants who took the drug strictly according to schedule and did not miss doses were up to 73 percent less likely to become infected. Adherence is a challenge across the board, however. About 50 percent of iPrEx participants were estimated to be adherent to the study protocol.

Other studies enrolling both women and men have also produced encouraging effectiveness data. In Partners PrEP, a study enrolling couples in which one partners was HIV-positive and the other was HIV-negative, effectiveness was shown to be 75 percent and adherence was estimated at 80 percent. The Centers for Disease Control and Prevention’s (CDC) TDF trial also showed adherence of about 80 percent, and the HIV risk of participants using the product was lowered by 63 percent.

So why is it that the two studies conducted exclusively among women did not yield evidence of effectiveness, when other studies enrolling both women and men did? What are the barriers to adherence that result in women finding themselves unwilling or unable to use this intervention daily? No answers to these questions are immediately apparent, although both the VOICE and the FEM-PrEP data are being further analyzed to look for clues.

If PrEP works for women (and men) when they use it, then why don’t women use it? Finding these answers will likely require additional research into the structural and cultural factors that shape behavior, perceptions of risk, and decision-making about sexual and health issues.

The U.S. Women and PrEP Working Group, a coalition of more than 50 women from leading AIDS and women’s health organizations, released a position statement this week highlighting factors likely to shape PrEP use (or lack of use) among women domestically. Working group Chair Dazon Dixon Diallo, the founder and president of SisterLove, Inc., observed that “[w]hile the clinical science is clear, the social and behavioral implications are less so, and we now need to develop and fund demonstration projects that will help answer a range of questions about real-world use of PrEP by American women and move toward an integrated plan for PrEP rollout in our communities that includes support for healthcare providers, social workers and others who will help women use PrEP effectively.”

Manju Chatani-Gada, senior program manager at AVAC and co-convener of the working group, added that “we have much work to do to understand what social, cultural and other factors affect adherence to the prescribed dose and how we can support women in effectively using new prevention tools. But PrEP remains a valuable option for many women who will want to and can use it as prescribed. Well-designed demonstration projects will help us understand adherence and other real-world issues for women who choose to use PrEP.”

The working group is calling for a coordinated, timely, and adequately funded domestic response to PrEP for women—a response that involves the full participation and leadership of individuals and communities most in need of effective, comprehensive HIV prevention. Its statement calls on the White House’s Office of National AIDS Policy and the CDC to work with the group to develop a national coordination plan for how Truvada will be rolled out to U.S. women.

Given that no clinical trials on PrEP have enrolled American women, the Working Group points out that there is a complete lack of evidence regarding how daily PrEP can best be promoted, made accessible, and financed in ways that ensure its uptake among U.S. women who want to use it and can benefit from it. Prompt action is required to fill the gaps in PrEP research, public and provider education, social marketing, and public policy. All of these are needed to support the next steps in developing a comprehensive roll-out plan for PrEP among women at high risk of HIV in the United States.

Preliminary social science research done on U.S. women and PrEP shows that most women surveyed had never heard of PrEP. After being informed, however, they expressed interest in using it if it were shown to be effective and promoted by people they know and trust. These data were gathered from 92 women in four U.S. cities. Key concerns that women expressed included cost, effectiveness, and side effects, including concern about possible interactions with hormonal contraception.

The working group’s statement raised a number of additional concerns that women have expressed anecdotally with regard to PrEP use, including:

  • Will some sex workers be pressured by their employers or managers to use PrEP because male clients dislike condoms?
  • Will some women be pressured by their partners to use PrEP instead of condoms?
  • Are there possible interactions between Truvada and the female hormones many transgender women use?
  • Will there be drug interactions between PrEP and recreational drugs?
  • Are there long-term health effects from Truvada for children whose mothers use PrEP during pregnancy or breastfeeding? How can these be tracked beyond the first year of life covered by current PrEP registries?

These real-life concerns directly affect interest in PrEP among women at high risk of HIV.  Failure to find answers, and to educate care providers so they can discuss PrEP knowledgeably with women patients, will discourage women from using this effective HIV prevention tool. Ignoring these gaps brings us to a future point of wondering domestically, “If it works when women use it, why don’t women use it?”

Women living with HIV in the United States have higher death rates than their male counterparts, higher rates of hospitalization, and experience more than twice as many HIV-related and AIDS-defining illnesses per person than their male counterparts. In 2008, nearly two-thirds of them had annual incomes below $10,000, compared to 41 percent of men living with HIV. Nearly three-quarters of women living with HIV had a high school education or less.

Most women living with HIV in the United States are already heavily disadvantaged. It is important that we not let lack of access to PrEP—because women aren’t hearing about it from their peers and community-based organizations, they can’t get their questions about it answered, they can’t afford it, or their health-care providers aren’t offering it to them—be added to the long list of disadvantages they currently encounter. We cannot let PrEP become a prevention tool regularly accessed by affluent men at risk of HIV, but not women.

“Male and female condoms are wonderful HIV-prevention options that work for many women and their partners. But some women can’t insist their partners use condoms, and many young women and their HIV-positive partners want to have children,” said Erika Aaron, a nurse practitioner at the Drexel University School of Medicine’s Division of Infectious Diseases and HIV Medicine. “Those women need other options to protect themselves from HIV. PrEP can help them stay HIV-negative. We have a moral imperative to find ways to make it available to women who need it and who can use it.”