Philadelphia Inquirer examines developments, ethics in microbicide research

The Philadelphia Inquirer on Monday examined issues surrounding microbicide research, including recent developments and ethical issues.

The Inquirer reports that the use of microbicides to prevent the spread of HIV "seemed so simple" 15 years ago, when researchers thought they could provide a vaginal gel that would be applied prior to sex. The gel would be "cheap and nonprescription, provide contraception and prevent many sexually transmitted infections, not just HIV," the Inquirer reports, adding that women also would be able to control its use, making microbicides "popular in places where men did not like wearing condoms -- that is, everywhere."

However, "the field's record is so disappointing that anything short of failure is cause for cheers," the Inquirer reports. More than $1 billion has been spent on research and development goals worldwide, with tens of thousands of women participating in clinical trials for potential microbicides that include things like lime juice, a seaweed extract and grain alcohol. The most recent development occurred in February when the International Partnership for Microbicides announced that an experimental gel -- PRO 2000 -- for the first time "had shown a hint more protection" against the virus than a placebo, according to the Inquirer. The trial -- which was conducted by researchers in Africa and Philadelphia -- was called "an important milestone," and Lisa Maslankowski, a researcher at the University of Pittsburgh who participated in the study, said that the PRO 2000 study was "the first time we've seen any signal of effectiveness, so this is very exciting for the field."

However, the results were statistically insignificant and indicated the gel's success "could have been a fluke," according to the Inquirer. The results from an ongoing trial of low-dose PRO 2000 are expected in late 2009. It would be considered statistically significant if the results showed a 33% decrease in HIV incidence, "a smidgen more than in the Philadelphia-Africa study," which could "pose another quandary," the Inquirer reports. Rowena Johnston, vice president of research at amFAR, said, "If we put out a marginally effective product, we know people would reduce their condom use. Then HIV infection would increase instead of decrease."

Advocates for microbicides are "undaunted," and there is a "new hope" that antiretroviral drugs could be used to prevent transmission of the virus. Still, "no one believes it will be simple," and many experts say the "science behind many studies was weak, the ethical quandaries were underestimated, and the basic rule of product development -- find out what the consumer wants -- was ignored," the Inquirer reports. In addition, microbicide research is "full of ethical and real-world dilemmas," including the fact that "developers cannot knowingly increase HIV risk while seeking a way to reduce it," the Inquirer reports. Women therefore are provided with condoms and "strenuously counseled to persuade their partners to wear them," but for some women in low-income countries their "only leverage may be the nominal payment" they are given for participating in the study. Anna Forbes, deputy director of the Global Campaign for Microbicides, said that women "can sometimes get their partners to use condoms during the trial because they are making money" but that condom use ends after the trial is over. Forbes said it is a "gray area ethically."

The failures of previous studies have led researchers to "now realize they need to come up with products that are not just good for women, but that women feel good using," the Inquirer reports, adding that once-daily formulations and slow-release vaginal rings are "in the works." Sharon Hillier, head of the federal Microbicide Trials Network and a researcher at the University of Pittsburgh, said the past decade "showed us there's no magic bullet." She also said that successes in preventing mother-to-child transmission through antiretrovirals have led researchers to explore pre-exposure prophylaxis. The Inquirer reports that this is a "radical shift," as the drugs are "neither cheap nor nonprescription" and come with "the danger of unintended consequences." Forbes said, "In poor countries, what are the odds that prevention pills would be taken from a woman and given to a family member with HIV?" In addition, there is a concern that expanded use of antiretrovirals could led to drug resistance, "undermining treatment as well as prevention," the Inquirer reports (McCullough, Philadelphia Inquirer, 3/23).