Microbicides Trials Produce Mixed Results, Raise Ethical Issues
Seventeen years ago, a Ugandan woman, a peer educator in her community, stood up at the 1991 AIDS Prevention 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 most new HIV infections occur among women and where a young African girl is now much more likely to get HIV than an African boy, finding new, effective methods of HIV prevention has never been more urgent.
One of the answers may be found in microbicides. Microbicides are substances that can prevent HIV (and possibly other sexually transmitted infections) from spreading. 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. (For more on microbicides, visit www.global-campaign.org.)
More than 1,200 people gathered in New Delhi, India, on February 24-27, 2008 for the Microbicides 2008 Conference (M2008) to discuss recent developments and determine the way forward. Participants in the conference learned the latest facts about antiretroviral-based microbicides and talked about their concerns. Advocates spoke about the ethical issues involved in microbicide research and the need to include the voices of HIV-positive women. Researchers shared the results of the first microbicide trials.
Carraguard Trial Results
Although two microbicide trials ended prematurely in 2007, a major trial to test a possible microbicide called Carraguard, begun in 1996 by the Population Council, finished on schedule. This was a milestone in itself because microbicide trials are very difficult to conduct. People participating in trials may not use the products correctly, so researchers need to test a very large group. In the Carraguard study, more than 6,200 participants were followed for up to two years.
The trial showed that Carraguard was safe and acceptable to women, but it did not show that it kept women from getting HIV. This was disappointing to everyone who had been watching the progress of this possible microbicide for 12 years.
The 2007 trial results can teach us how to adapt our research so that it better responds to some of the challenges seen. For example, we saw that people had a difficult time sharing personal information about their sex lives, including how they use the study products during sex. Without this information, we cannot tell if a product does not work because of a problem with the product itself, or because it wasn't used consistently or correctly.
As every doctor knows, most people do not tell the truth about sex. We also have different ideas of what sex is. And many of us tell people what we think they want to hear. In order to deal with these realities, researchers have developed creative research strategies. Some trials have used computers for the interviews, since people may be more honest with a machine than with an individual asking personal questions. Another trial has people answer the questions on special Blackberries (remote communication devices).
The microbicide field is also focusing on a new class of products, ARV-based microbicides. The first trial of an ARV-based microbicide was started in 2007 by the Centre for the AIDS Programme of Research in South Africa. Almost 1,000 South African women will be involved in testing a gel that is vaginally inserted before and after sexual activity. A number of other ARV-based microbicide trials are also being planned.
While the new ARV-based microbicides are very exciting, concerns about the potential for drug resistance are being raised. If someone is HIV-negative while using an ARV-based microbicide, drug resistance will not be a problem. But 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 during every single sex act? What if she does not know her HIV status or knows she is positive but uses the microbicide to try to protect her partner? Is it possible that the HIV in her body will learn to fight off the ARV in the microbicide and, if so, will this affect her future treatment? The likelihood of this depends on how much of the ARV in this microbicide is absorbed into the user's bloodstream. Researchers are now trying to figure this out.
Women attending the HIV-Positive Roundtable at M2008 in New Dehli discussed, in depth, their concerns about resistance to ARV-based microbicides. Researcher Jeanne Marrazzo noted that resistance is a concern on everyone's minds, and that researchers will do everything possible to prevent resistance by "giving people monthly HIV tests and giving people only a month supply of [microbicide study product], to help minimize the likelihood that [women] will be on a test product for any length of time while HIV-positive."
HIV-positive women in attendance 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," and urged researchers to involve positive women at all levels of planning and implementation.
Ethics of Clinical Trial Research
Another topic that received considerable attention at the M2008 Conference was the standard of care provided to women who seroconvert (become HIV-positive) in the course of their study participation, and the ethical obligations of researchers to provide them with care.
Women in the Carraguard trial -- both those who seroconverted (were diagnosed with HIV during the course of the trial) and those who tested HIV-positive at initial screening -- were referred to medical, psychological, and supportive services in their communities. Some of the trial sites offered additional services including CD4 (t-cell) counts, nutritional counseling, physician check-ups, and support groups. Women who seroconverted were also invited to come back to the study clinic after the trial was over for an additional follow-up visit. At these visits, they were offered CD4 counts, Pap smears, testing and treatment for sexually transmitted infections, counseling, and, for women who were medically eligible, direct referrals to government antiretroviral treatment programs.
But how do trials meet the needs of participants who remain HIV-negative throughout the trial and their partners -- as well as those who seroconvert during the study and those who "screen out" (cannot join the trial) because they are already HIV-positive? The Global Campaign for Microbicides presented preliminary findings from a 2006-2007 Standard of Care mapping exercise they conducted to learn more about this. Through independent assessment of the health care and prevention services provided in trials, the mapping sought to better understand how care-related decisions at trial sites are made. It also assessed how much progress is being made toward achieving the ethical aspirations laid out in key ethics guidance documents. Thus, it provides a basis for recommendations to strengthen the field's ability to respond to care-related challenges in future trials.
Katie West is a Program Associate at the Global Campaign for Microbicides.
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This article was provided by Gay Men's Health Crisis. It is a part of the publication GMHC Treatment Issues. Visit GMHC's website to find out more about their activities, publications and services.