Throughout history, women have been excluded from clinical research studies, resulting in a dearth of knowledge about the effect that drugs might have on different sexes. This gender gap is especially obvious when looking at diseases such as HIV and heart disease, which have traditionally been seen as men's health issues.
However, we now know that HIV-positive women are three times as likely to suffer from heart disease as women without HIV. In the U.S., about a quarter of all HIV-positive people are women, and globally, women make up about half of all people living with HIV. Thanks to antiretroviral therapy, many of these women are living longer lives, but they may develop other health problems, such as heart disease, at a younger age than their peers.
Now, a federally funded study called REPRIEVE is seeking to explore the interplay between HIV and heart disease in both men and women, as well as to determine whether a commonly prescribed cardiovascular medication called pitavastatin could stave off heart attacks and strokes among older people with HIV. Meanwhile, a sub-study of the trial will evaluate the effects in women specifically, monitoring things such as hormone levels and menopause that may also impact heart attack risk and the effects of medication.
REPRIEVE is an ambitious trial that seeks to enroll 6,500 patient volunteers, and investigators "are hoping to enroll as many women as possible," according to Sara Looby, Ph.D., ANP-BC, FAAN, one of investigators in charge of the REPRIEVE sub-study focused on women. The study is sponsored by the National Institutes of Health (NIH) with support from the National Institutes of Allergy and Infectious Disease (NIAID), and it is being conducted through the AIDS Clinical Trial Network.
"Women have historically be absent from research studies like this for a variety of reasons," said Anthony Fauci, M.D., NIAID director. "Women tend to focus more on taking care of others -- their children and loved ones," Fauci said. In addition, "some trials don't actively recruit women" because of legitimate worries about pregnancy and fetal harm.
REPRIEVE will be different, said Fauci. "In our trials, we've tried very hard to recruit women," he said. So far, about 36% of the people enrolled in the trial are women, and the study is currently still enrolling participants, according to the REPRIEVE website.
Looby, who is based at Massachusetts General Hospital, has been championing the effort to bolster women's participation in the REPRIEVE study. She and her colleague, Markella Zanni, M.D., surveyed a diverse group of 40 older women to learn about the main barriers to enrolling in a trial.
According to Looby, women -- especially older women -- face several barriers when it comes to enrolling in research. The first is that their doctors simply don't mention it to them. "They hadn't been told ...[;] that was one of the main reasons they didn't join," she said.
The second reason is that women are more often caregivers and may not advocate as strongly for their own care. "I hear a lot that women don't always put themselves first; they're always caring for others," she said. In addition, there may be trust issues related to clinical research, especially for women of color who have seen trust betrayed by unethical experiments on minorities in years past.
"We've had to … make special efforts to get women of color involved," said Fauci. "Superimposed on the standard situation of women worrying less about themselves, … the African-American community in general often has mistrust in the scientific enterprise of clinical trials because of the egregious violations of trust that have occurred in the past," he said.
Based on the insights Looby and Zanni gleaned from their survey, they created an evidence-based education campaign called Follow YOUR Heart aimed at encouraging HIV-positive women to enroll and educate themselves about cardiovascular risk, with information distributed via promotional materials, an informational film, and an online resource center. Meanwhile, Looby and her colleagues have been working with HIV advocacy organizations such as Older Women Embracing Life (OWEL) and Healing Our Community Collaborative (HOCC) to spread the word about REPRIEVE.
Both OWEL and HOCC are nurse-led peer support programs, which is a perfect place to promote a clinical research program like REPRIEVE, said Looby. When making a big decision -- such as whether to join a research study -- women involved in these networks can "get reassurance and perspective from their peers that are validated by the clinician in the room," said Looby. Having that support "just makes women feel better," she said.
REPRIEVE is still looking for volunteers -- especially HIV-positive women between the age of 40 and 75 who have been on antiretroviral treatment for at least six months and have no prior history of heart disease. Prospective volunteers can visit this map to find a study location nearby.
Broadly, the NIH and NIAID are making an effort to build trust among women and make it easier for them to enroll in clinical research. That's because when "you get a drug that's approved based on predominately studies in men, it may take you years to realize you're dealing with the wrong dose or some toxic side effects in women," said Fauci.
He emphasized that when women are underrepresented in trials, "We don't even know what we're missing."