With reports earlier this year purporting of a second person having achieved complete HIV eradication (although experts cautioned it is way too early to declare the subject “cured”), the global scientific community is working harder than ever to find a functional cure for the virus. In order to do so, researchers are beginning to realize they have to deal with a long-ignored demographic: women.
Although women make up just over half of the nearly 37 million people living with HIV worldwide, there is a noticeable lack of women involved in the research of potential treatments, cures, and vaccines, according to a recent in-depth report by The New York Times.
Globally, HIV is the leading cause of death among women of reproductive age. The epidemic continues in part because of new diagnoses among young women in Africa, parts of South America, and even the Southern United States.
Yet, a 2016 analysis by amfAR found that in trials of HIV cures, women accounted for only a median 11 percent of participants. In trials of antiretroviral drugs, 19 percent of the participants were women. Vaccine studies were the closest to having equal gender representation, with 38 percent female participation.
“If we’re going to find a cure, it’s important that we find a cure that actually works for everybody,” Rowena Johnston, director of research at amfAR, told the Times.
There are differences in the immune systems of men and women, including the response to HIV. Women’s immune systems often respond strongly to HIV at first, with strict control over the virus for five to seven years. But after that, women seem to progress faster to late-stage HIV (or AIDS) than men do and are at greater risk of heart attacks and strokes.
“There are all sorts of differences between men and women, probably mediated partially by hormonal effects,” Dr. Monica Gandhi, professor of medicine at the University of California, San Francisco, told the paper. For example, estrogen, a hormone that women have higher levels of, appears to contribute to HIV dormancy, enabling the virus to hide from drugs and the immune system.
Gender differences have been observed even among prepubescent children. One study found that among 11 children who were “elite controllers” — those able to suppress HIV to undetectable levels without drugs — 10 of them were girls.
Some drugs affect women and men differently. Children born to women taking dolutegravir, for instance, may have a higher risk of neural tube defects, while women taking nevirapine were much more likely to have a severe rash than men using the drug. Yet, the Times report notes, “Men accounted for 85 percent of the trial subjects in which these drugs were tested.”
This may seem like it’s related to the apparent concentration of HIV among gay men (at least in the U.S.) but the truth is, these numbers reflect a widespread bias in medical research to accept the male body as the standard for testing and dosage recommendations.
Still, it is true that gay men in the U.S. have organized and fought to get into drug trials since the early 1980s, and are connected to support networks that share news of clinical trials. And they often live in the urban settings where most research happens. Women with HIV usually have fewer connections and may be less likely to make demands to the health care system. Lack of child care or transportation or discomfort with male doctors may keep some from clinical trials, and trial sponsors don’t often make provisions to help more women participate.
For women of color, there are even more obstacles involved when navigating a health care system that has ignored and exploited them for decades. “[There’s] a lot of stigma still in our community around research,” Ublanca Adams, 60, a California woman living with HIV, told the Times. “How information is given out to our community and our people is just not in a way to be inclusive nor is it inviting.”
Furthermore, the Food and Drug Administration’s rules limit the testing of drugs on cisgender women of childbearing age due to the potential for unplanned pregnancies. No one wants to deal with how an investigational drug might impact a developing fetus.
The restrictions have led some researchers, including Dr. Eileen Scully, assistant professor of medicine at Johns Hopkins University, to recruit menopausal women. But because these participants have lower levels of circulating estrogen, the results may not be applicable to younger women.
Ultimately, most researchers take the easy way out and do drug trials on men. Information on how a drug affects women comes in only after the drug is on the market. An increasing number of studies include trans women, but they remain relatively rare. In the past, trans women were often lumped in with gay men, even though their response to medications can also differ widely from that of cisgender men.
Two recent trials of long-acting injectable HIV drugs managed to recruit significant numbers of women (33 percent were female in one study, 23 percent in the other), most likely due to the promise of less frequent treatment — a big convenience for, say, an overwhelmed mother.
“Patients lined up outside the clinic,” said Dr. Kimberly Smith, head of research and development at ViiV Healthcare, which led the research. But trials in the U.S. generally have few female enrollees, Smith said, because about 75 percent of those living with the virus in this country are men.
There are efforts to address the male-female disparity overseas. Dr. Bruce Walker and his colleagues at the Massachusetts-based Ragon Institute have set up a group in South Africa called Fresh, bringing nearly 2,000 young women in for HIV testing twice a week. The researchers provide preventive therapy and track diagnoses, and they plan to test potential cures in the group.