Microbicides: Looking Back While Moving Forward
Seventeen years ago, a Ugandan woman stood up at a conference and asked, "If they can put a man on the moon, why can't they make something we can use to protect ourselves from HIV?" Since then, researchers and advocates have tried to answer her call. In a world where a young African girl is much more likely to get HIV than an African boy, finding the answer has never been more urgent. One of the answers may be microbicides. Microbicides are products that can prevent HIV infection, and possibly other sexually transmitted infections. Some are designed for vaginal use and some for rectal use. They may take the form of gels, creams, suppositories, films, lubricants, or even a sponge or a vaginal ring.
Over 1,200 people gathered in New Delhi, India, last February at the Microbicides 2008 Conference (M2008) to discuss recent developments and next steps. Researchers shared the results of the first microbicide trials and presented updates on antiretroviral-based microbicides. Advocates spoke about ethical issues and the need to include more voices, especially those of women with HIV.
The Challenges of Clinical Trials
Although two microbicide trials ended prematurely during 2007, a large trial of a microbicide candidate called Carraguard recently finished on schedule. This was a milestone in itself because microbicide trials are very difficult to conduct. People in the trials may not use the product correctly, so researchers need a large group. In the Carraguard study, there were over 6,200 women who were followed for up to two years. The trial found that Carraguard was safe and acceptable, but that it did not prevent HIV. This was of course disappointing to everyone who had been watching this microbicide for over ten years.
These trials also provided information on how to adapt research so that it responds better to some of the challenges that arise. For example, people in the Carraguard trial had a hard time sharing information about their sex lives and how they used microbicides during sex. But without this information, studies can't tell if a microbicide fails because of a problem with the product itself or because it wasn't used consistently or correctly.
As every doctor knows, most people don't tell the truth about sex. They also have different ideas of what sex is. And most people tell researchers what they think they want to hear. There are various ways to deal with these problems. Some trials use computers for the interviews, since people may be more honest with a machine than with a person. In addition to asking people whether they used the microbicide, one trial tested the microbicide applicators to see if they had been used. Another trial let people answer the questions on a portable keypad device.
Community members and women's groups can provide valuable insights into how various factors and research decisions can affect adherence (consistent use of study products) and retention rates (the ability to keep participants enrolled in trials). By involving the community, researchers can ensure that their desire to obtain accurate trial results does not unnecessarily burden or stigmatize the women volunteering for the trial.
Microbicides that would prevent HIV infection by using some of the same antiretroviral drugs (ARVs) that people with HIV use are also being studied. The first trial of an ARV-based microbicide began in 2007 by the Centre for the AIDS Programme of Research in South Africa (CAPRISA). Almost 1,000 women are testing a gel that is applied in the vagina before and after sex. Other ARV-based microbicides are also being studied.
While the potential of these new microbicides is exciting, concerns about the potential for drug resistance are being raised. What happens if a woman becomes infected while using an ARV-based microbicide, either because the microbicide did not work or because it was not used every time she had sex? What if she knows she is HIV-positive but uses the microbicide to try to protect her partner? The HIV in her body could become resistant to the ARV in the microbicide, limiting her future treatment options. The chance of this happening depends on how much of the ARV in the microbicide is absorbed into the bloodstream. Researchers are now studying this.
Another important question about microbicide testing is whether or not the women in the trials will be able to get treatment if they become HIV-positive during the study. Much more discussion is needed around this issue.
Women with HIV at the M2008 conference raised concerns about resistance to ARV-based microbicides. Researcher Jeanne Marrazzo noted that resistance is on everyone's mind and that researchers will do everything possible to prevent it. People will be given monthly HIV tests and receive only a month's supply of the microbicide, to reduce the chance they will use it for too long while HIV-positive.
HIV-positive women also expressed concern that microbicides were only being developed for HIV-negative women. Louise Binder, a well-known Canadian activist, warned researchers not to "make the same mistake that was made with treatment fifteen years ago - failing to take us up on our offer to get involved with shaping trials." She urged researchers to involve women with HIV when planning and running studies.
Ethics of Clinical Trial Research
Another topic that received considerable attention at the M2008 Conference was the healthcare offered to women who become HIV-positive during the study and the ethical obligations of researchers to provide them with care.
Women who became HIV-positive during the Carraguard trial and those who tested positive at the start were referred to medical, psychological, and supportive services in their communities. Some of the trial sites offered additional services, such as CD4 T-cell counts, nutritional counseling, medical check-ups, and support groups. They were also invited to come back to the study clinic after the trial was over for follow-up visits. At these visits, they were offered CD4 counts, Pap smears, testing and treatment for sexually transmitted infections, counseling, and referrals to government HIV medication programs.
But how do trials meet the needs of those who stay HIV-negative during the trial and their partners? At M2008, The Global Campaign for Microbicides presented findings from a 2006-2007 study of the healthcare and prevention services provided in trials. This survey looked at how healthcare decisions are made at trial sites. It also assessed how much progress is being made toward achieving the ethical goals laid out in key guidance documents. It offered recommendations to strengthen the ability to respond to health care-related challenges in future trials.
The Role of Civil Society
Civil society includes people who are involved, often through nongovernmental organizations, in trying to influence government policy or business practices. At M2008, one thing was clear: Civil society's role in microbicides research is expanding, and is increasingly important to donors, researchers, and research institutions. The impact of civil society was the topic of a day-long event at the conference attended by almost 200 advocates. The first-ever "Advocate's Corner," a collaboration between seven civil society groups, offered advocates a way to share their work and materials, network with each other, and participate in skills-building workshops, including question-and-answer sessions with researchers.
Specific groups such as rectal microbicide advocates, sex workers, and women with HIV were also more visible and vocal than ever before. But more collaboration between civil society and researchers is still needed. We must ensure that these voices are not only heard, but are equal participants in the search for an effective microbicide. For more information about the Global Campaign for Microbicides and how to get involved in microbicide advocacy, visit www.global-campaign.org.
Katie West is a Program Associate at the Global Campaign for Microbicides.
This article was provided by ACRIA and GMHC. It is a part of the publication Achieve. Visit ACRIA's website and GMHC's website to find out more about their activities, publications and services.