PrEPared to Fight: A Woman-Centered Approach to HIV Prevention
In 2000, Poppy Hillsborough* entered an office at San Francisco General Hospital with babies on her mind. Her boyfriend, Ted Morgan,* has HIV, and she wanted to know if she could have children with him without adopting or using expensive reproductive technology. If she thought of HIV medications at all, it was because they were keeping Morgan healthy. As far as Hillsborough was concerned, babies and meds were two different issues.
Until they weren’t.
It took a decade and lots of false starts, but in 2010, Hillsborough and Morgan, now married, started trying for a baby. Once a month when Hillsborough was ovulating, the couple would leave the condoms aside and have sex once. They did it off and on for months, all with the hope, Hillsborough said, that she could have a baby with the sandy blond hair and lanky build of her husband. What made their experiment possible was a medication, Truvada, that Hillsborough took daily and that promised to reduce her risk of contracting HIV.
The fact that it was an HIV medication didn’t seem real to her—at least not until her husband started taking it to manage his virus, as well.
“All of a sudden, it was very clear that this was an HIV treatment medication,” she said. “It made the risk we were taking feel very real. Up until then, it had felt kind of hypothetical. I realized, ‘If I do get infected, this is what I might be taking.’”
Hillsborough was an early pioneer in a prevention method called pre-exposure prophylaxis, or PrEP. At the time she used it in 2010, the Food and Drug Administration had not yet approved Truvada for the purpose and she had a hard time getting doctors to prescribe it for her. After the FDA’s approval in 2012, PrEP use increased more than eight-fold, going from about 150 users in 2011 to 1,274 users the following year. And nearly half of those users, 48 percent, were women.
That number surprised some, considering that the majority of the conversation about PrEP to that point had been conducted within and between members of the gay community. But it turned out that there was another group waiting to use it: women, many of them in relationships with HIV-positive men, who wanted to conceive safely or simply reduce their risk of contracting the virus. The surprising interest women showed in PrEP underlines the lack of control women have had over their sexual health in the past, said Dr. Gina Brown, an ob-gyn and a medical officer in the National Institutes of Health’s Office of AIDS Research.
“Before PrEP there were no real options for women, in the sense that when we talked about prevention options before, the message was always, ‘Use a condom,’” said Brown, who manages planning for studies of women and girls HIV treatment and risk. “But women don’t use condoms; men do. And even female condoms require cooperation from men.”
Indeed, whether PrEP is used for conception, as prevention soon after the man is diagnosed, or at other points in a couple’s life cycle, PrEP puts the power of prevention in women’s hands.
PrEP’s Bad Rap for Women
Judy Auerbach noticed a trend at the 2013 Conference on Retroviruses and Opportunistic Infections (CROI). When speakers approached the mic with questions, or shared casually between sessions, there was a common—and erroneous—assumption underpinning their statements.
“The spin became, ‘PrEP doesn’t work in women,’” said Auerbach, a professor in the School of Medicine at UC San Francisco and former vice president of research and evaluation at San Francisco AIDS Foundation. “I don’t know how it morphed into that. People are quick to say that the trials failed, or that PrEP doesn’t work in women, when neither is true.”
The bad rap goes back to 2011, when the Vaginal and Oral Interventions to Control the Epidemic (VOICE) and FEM-PrEP trials both closed because reviews determined the studies were unlikely to demonstrate efficacy. This was a shocking blow, considering that, in 2010, the Chemoprophylaxis for HIV Prevention in Men, or iPrEx, study had found that PrEP reduced HIV transmissions in men who have sex with men and transwomen who have sex with men by an average of 43.8 percent overall, and more than 90% in those whose drug levels in blood samples indicated daily or near-daily adherence.
Could it be that Truvada somehow didn’t work in women when it worked in cis-gendered men and transwomen? No. VOICE and FEM-PrEP weren’t discontinued because the drugs didn’t work in women.
They were discontinued because the .
In the VOICE trial, for instance, fewer than a third of the women took oral Truvada daily as prescribed. In FEM-PrEP, study subjects took the medication the equivalent of less than twice a week, when they were instructed to take it every day. Considering that iPrEx showed that the more faithfully you take Truvada the better it protects you from HIV infection, the lack of adherence made it nearly impossible to draw any conclusions about efficacy from VOICE or FEM-PrEP.
Other studies have been more definitive. Partners PrEP, which followed the PrEP usage of HIV-different couples in Africa, found that Truvada reduced the risk of transmission by 75 percent, with adherence rates of 81 percent. Meanwhile, the TDF2 study, which followed young adult heterosexual men and women in Botswana, found that, when both men and women took Truvada up to 81 percent of the time, they could reduce risk of transmission by 62 percent. The results weren’t significantly different between women and men. So we know PrEP works in women, said Auerbach.
If anything, the so-called failure of VOICE and FEM-PrEP only proves that medications can’t work if you don’t take them, she said.
“In both Partners PrEP and TDF2, the effectiveness of PrEP was pretty high for women,” said Auerbach. “But we hear less about those than we did about the trials that just enrolled women.”
The Power of Choice
On a recent webcast hosted by the nonprofit HIV prevention group AVAC, Dr. Nika Seidman recalled a 38-year-old woman who recently found her way to Seidman’s office at the Bay Area Perinatal AIDS Center (BAPAC) at San Francisco General Hospital. The woman had recently moved from Guatemala to reunite with her husband, who had contracted HIV in their time apart. She was in Seidman’s office not because she was worried about HIV but because she wanted to have another child.
“She felt grateful to have a conversation because she had previously thought that, in many ways, she’d never be able to have a family safely while staying HIV negative and having a negative child,” Seidman said in the webcast, aimed at physicians who wanted to know how to prescribe PrEP accurately. “A lot of the women who come to us for preconception counseling are excellent pill takers and are very interested in being compliant. She assured us that she could take a pill every day, that it wasn’t an issue.”
But before they could discuss PrEP for pregnancy, they had to make sure the woman was HIV negative. This is important because Truvada alone is not enough to treat HIV infection, said Seidman. Three weeks before the Guatemalan woman visited Seidman, a condom broke while the woman and her husband were having sex. So they tested her for HIV and encouraged her to bring her husband to the next appointment.
When she came back the next time, the conversation shifted. It turned out that her husband hadn’t been to see his doctor in six months, so they didn’t know his viral load—that is, how much virus was in his system. HIV treatment can reduce viral load to undetectable amounts, concomitantly reducing the risk for transmitting the virus to a partner. And she learned that condoms had been breaking more often than she’d realized.
“Basically, she found out that she was not as fully aware and didn’t have as much power in the relationship as she’d previously understood, in terms of protecting herself,” Seidman said. “So the conversation moved from PrEP for preconception to the use of PrEP in general. We moved on to a conversation about when was the right time to start PrEP with ongoing exposure.”
That’s exactly how it happens a lot for women, said Dr. Mina Matin, director of the Family HIV Clinic at San Francisco General Hospital. PrEP is a tool, and it can be employed at many times in the course of a woman’s life. Both she and Seidman said that the majority of women who contact them about PrEP do so in the service of having a baby.
But that’s not the only time PrEP can be useful. PrEP might be called for as an additional protection against infection if the positive partner’s virus is difficult to suppress. It’s also helpful when a woman’s partner is newly diagnosed with HIV, for instance, when the amount of virus present may be at its highest level. PrEP can be a useful way to protect a negative woman while the positive partner becomes engaged in care.
It’s also useful if the man doesn’t want to engage in care or has fallen out of care—but only after the woman, like the woman Seidman described, has tested HIV negative. Sometimes this means a woman might take PEP—a 28-day course of triple-drug antiretroviral therapy, started within 72 hours of exposure to HIV, to prevent infection—and then start on Truvada as PrEP after testing negative. Sometimes it means starting a woman on PrEP immediately, once it’s clear that she hasn’t been recently exposed to the virus and does not have HIV.
PrEP, like treatment for the positive partner, can help stabilize both health and the relationship, said Matin.
“As their story unfolds and their engagement in care unfolds, we like to revisit the discussion of the risks and benefits of PrEP in the relationship,” she said. “It may be that PrEP continues as part of the relationship because of factors in the relationship. Or it may be that PrEP is no longer needed.”
Those factors and those decisions will depend on the individual couples and the woman’s comfort level with risk.
But there’s also another time when PrEP may be indicated, she said. It may be that PrEP becomes an option in the middle of a relationship, when something triggers feelings of mistrust or fear, such as an affair or, as with the woman Seidman described, when she finds out that her partner has been less than honest with her about how safe she’s been during sex with condoms. Though she said they often try to work with both members of a couple, women sometimes elect to start taking PrEP without consulting their partners. It’s a personal decision, as is the positive partner’s decision to engage in treatment.
“It can be a private part of the relationship,” Matin said. “She has control over it. She can decide if she needs to be on PrEP. She can take her medication. She doesn’t necessarily need to involve him.”
The result of that sense of control can be surprising, doctors said. Women who’d previously had to rely on their boyfriends or husbands to use a condom—and use it correctly—can relax a little more. They don’t have to act as the pill police, monitoring their partner’s adherence to their medication because they know it’s the primary way to protect themselves from infection.
“It’s not just the prevention of HIV that PrEP allows,” Dr. Tony Mills, an HIV specialist in Los Angeles, told the AVAC webcast. “It’s also amazingly effective in allowing them to relax and enjoy a sexual encounter again. There’s a fear they hold on to when it comes to HIV acquisition. PrEP allows patients to connect more with their partners if that was something that kept them from being fully present.”
And for women trying to get pregnant, PrEP can change the conversation, said Matin.
“Once PrEP is started and continued in a stable fashion throughout the pregnancy, the focus can be more on building the new person inside the mommy,” she said. “There’s this reassurance that this baby is going to be born without HIV. The family has done everything it can to decrease the chance of transmission to the baby because the mother is not going to have HIV.”
A Few Unknowns
It’s not all rosy, of course. Truvada, though generally well tolerated, can have side effects. The most common ones, said Seidman, are headaches, nausea, and fatigue in the first month. These usually clear up after that and the women she’s treated haven’t had many other symptoms. In rarer cases, it can also cause liver and (reversible) kidney problems. And for women looking to use PrEP during pregnancy, some preliminary studies have found that babies born to women taking Truvada have slightly smaller head circumferences—less than a centimeter difference.
Truvada can also cause slight declines in bone mineral density in adults, although it’s hard to know what those finding mean for babies, said Seidman in the webinar, since babies aren’t typically measured for bone mineral density.
“We don’t understand the clinical significance of these differences,” she said. “We don’t know what’s normal.”
And then there’s the issue that Hillsborough identified when she and her husband were taking the same medication—the discomfort some people have with taking an HIV medication. It can be a serious cultural barrier to PrEP, said NIH’s Brown. In her work, she helps identify the big picture issues that the NIH ought to fund when it comes to women and HIV care and prevention. And she’s very interested in why the women in the VOICE and FEM-PrEP trials didn’t take their medications.
“We’ve shown that PrEP can work in women,” she said. “The difficulty was that, in some studies, it was not shown to be effective in women who are not part of a couple. The women who’ve been proven to take it are not the garden variety 20-year-olds you’ll meet at a club. What we need to know is why they didn’t take the drug. What else was going on? It could be as simple as, ‘Were they afraid of the side effects?’ Or, it could be as complex as, ‘They didn’t want to be seen taking HIV drugs.’”
To find out—and to ensure that the women at greatest risk of acquiring HIV have access to PrEP—we need to reach out to women, yes, but also to providers who provide care for HIV-uninfected women and those who influence their behavior, like family members and the community.
This can be difficult, since the stigma around HIV and sex in general exist both within and outside the medical community. When her husband’s HIV doctor advised her to try PrEP to have a baby, Hillsborough went back to her primary care doctor and asked if she would prescribe it for her.
“She said, ‘Absolutely not. I don’t think it’s an ethical thing to do,’” Hillsborough said. “And then she said that if I did it anyway, she wouldn’t treat me. I was asking for help reducing the risk for myself and she was saying, ‘Not only am I not going to do that, but you’re on your own.’”
Hillsborough’s doctor did not return calls seeking comment.
You might think that this was a rare case, from a time before FDA approval and greater knowledge about HIV prevention and PrEP. But almost every doctor who spoke to BETA for this article said Hillsborough’s story sounds familiar. When Dr. Stephanie Cohen was enrolling gay men and transwomen in a multicenter PrEP demonstration project funded by the NIH, she said many of her patients told her they’d previously asked doctors to prescribe PrEP, and were met with judgment.
“Doctors are risk-averse people,” she said. “Harm reduction as a concept is something that’s sort of been difficult for the medical community. There’s a provider stigma side of this, an attitude of, ‘Why would I enable their risk taking?’”
Part of the problem comes from something Brown said the HIV-treatment community has been a part of: Siloed care.
“Way back in the beginning, we treated HIV like it was something special,” said Brown. “We haven’t gotten rid of that.”
So now we’ve got a dilemma. HIV doctors are comfortable with Truvada but they don’t see HIV-negative patients. And doctors who do see HIV-negative patients may not be familiar or comfortable with PrEP. According to statistics from Gilead, the company that makes Truvada, the top three prescribers of PrEP are family practice doctors, internists, and emergency room doctors. And, tellingly for women, ob-gyns aren’t on the list at all.
“Where PrEP stands in terms of ob-gyns is that there are a group of us who have either done a reproductive infectious disease fellowship or have extensive clinical experience in care of women,” said Dr. Jenell Coleman, an assistant professor of gynecology and obstetrics at Johns Hopkins University in Baltimore, referring to a fellowship that she and others have done with BAPAC and other sites around the country to learn about maternal-fetal medicine in women affected by HIV. “We’re all aware; we’re prescribing it. But I don’t know any ob-gyns, except those who have done this fellowship, who feel comfortable prescribing or talking about PrEP.”
The American College of Obstetricians and Gynecologists (ACOG) changed its stance on PrEP in May 2014, moving from a wait-and-see approach that sited VOICE and FEM-PrEP as reasons to be cautious of PrEP to a stance that encourages ob-gyns to prescribe the medication and encourage daily adherence. The opinion states that doctors should counsel women on PrEP if their partners are HIV-positive, if they live and date in social networks and geographic areas with high incidence of HIV infection, if they inject drugs, or if they are dating someone whose HIV status they don’t know.
However, most doctors don’t ask their female patients if their partners are HIV-positive, said Shannon Weber, BAPAC’s coordinator.
Facing Down Stigma
And doctors aren’t the only ones judging the risks women are willing to take to have children or just to have sex with their HIV-positive partners. In communities of men who have sex with men, the slur “Truvada whore” has been used to describe men who use PrEP, with the assumption that they’re using it so they can be cavalier in their sexual behavior.
“When the [PrEP] trials first came out, that was part of the reticence around PrEP, even for gay men,” said UCSF’s Auerbach. “The fear was, ‘This is going to cause a sex panic.’ Some of the women in our groups said that. ‘This is risk disinhibition. It’s going to allow more people to have sex without condoms.”
Those “groups” were focus groups that Auerbach and her colleagues at AIDS United assembled to conduct qualitative research into women’s perceptions of risk and willingness to use PrEP. Women were asked if they’d heard of PrEP, what they thought of it, who they thought would use it, and whether they would take it themselves. While answers to whether individual women would take it varied, most thought that PrEP was something appropriate for all kinds of women, and that for some, this would be permission to stop using condoms.
“They started naming groups: ‘Promiscuous’ women, anyone having sex with more than one person, women using drugs, women who are in and out of prison,” said Auerbach. “We got the whole gamut.”
In many ways, the response to PrEP isn’t so different from the fear that arose over the introduction of birth control, said researcher Cohen, medical director of San Francisco’s City Clinic. Anything that makes it easier for people to have sex might lead to riskier behaviors, say the critics.
But Auerbach said that the analogy to contraception is apt in another way, too. There was backlash, yes, but in the end, what doctors and the public realized was that contraception took away one risk but not the others. Likewise, women taking PrEP still have to worry about other sexually transmitted infections and pregnancy.
“One can argue that no one is not having sex because they think they’re going to get HIV,” Auerbach said. “In the end, what [our focus group participants] decided was that PrEP would be good for any woman who was having sex who didn’t know her risk of contracting HIV.”
The Future of Woman-Centered HIV Prevention
In January, Johns Hopkins’ Coleman stood before a group of residents and talked to them about PrEP—what it is, when it’s indicated, and how to prescribe it. The discussion had a big impact on the physicians in training, she said.
“Now the residents all email me when they have a patient who might be good for PrEP,” she said. “Three women have been referred to me within the past three months.”
Across the country, doctors like Coleman are working hard to overcome the barriers to finding and treating women at highest risk for acquiring HIV. In addition to doing lectures for residents, Coleman is trying to add a section on PrEP to the medical school’s ob-gyn residency handbook. In Boston, Sullivan has been asked by the Massachusetts Department of Public Health to think about how to bring PrEP to the clinics where it’s needed most. And she is working to help front-line workers identify patients who come in for repeated STI tests and for PEP, to try to funnel them in to treatment and talk to them about PrEP.
In San Francisco, City Clinic’s Cohen has applied for a grant to do provider training and to create tools for those providers around PrEP. The proposal is now under review by the NIH.
And advocates are encouraging organizations like ACOG to issue practice guidelines, and bring up PrEP with their patients.
“There are some hopeful signs,” said NIH’s Brown. “We’re working to see about getting it into places where women get care, their family planning and women’s reproductive health care.”
The way women take PrEP may be changing, too. Researchers are looking into long-acting injectables along the lines of the Depo-Provera contraceptive shot. Others are working on a vaginal ring like NuvaRing that would deliver PrEP paired with contraceptive hormones in a single device, for multipurpose prevention technologies that may prevent HIV and pregnancy as well. Other formulations of microbicide gels that can be used rectally and microbicide-impregnated films could give women yet another option besides Truvada.
And then there’s the PrEPception study, soon to get underway at multiple centers across the country. The study will involve Johns Hopkins, Boston Medical Center, Drexel University, and San Francisco General Hospital, following women who choose to use PrEP during conception and pregnancy. The idea is not to test how well PrEP works per se—though they will be monitoring adherence and checking the level of the drug in the women’s systems. No, the study aims to establish a clinical protocol for PrEP that can be replicated elsewhere.
“Right now, these protocols only exist in certain areas, in big cities,” said Dr. Meg Sullivan at Boston Medical Center, chief investigator of the trial and an infectious disease specialist who has for decades treated HIV-positive women and negative women looking to get pregnant. “If we can create a pretty straightforward clinical protocol, we’re hopeful other doctors will see it and say, ‘It did very well. I feel like I could use this as a basis for my practice in Iowa.’”
The HIV-Negative Woman of the Future?
In a smaller conference room just next to a Starbucks and inside a large hotel in San Francisco’s Mid-Market neighborhood, a group of about a dozen women sat in a circle around a large table. Of the hundreds of people milling around the hotel’s ballroom, they were the only ones primarily focused on cis-women’s HIV prevention.
Each woman went around the room and introduced herself and her interest in the topic: The infectious disease doctor, the PhD, the HIV-positive activist, the head of a state HIV program. And then there was Caroline Watson, who followed the introductions and nodded along as the current research on PrEP was discussed. Her eyes darted between speakers, her brows furrowed slightly, and she raised her hand.
“Why do we need PrEP?” she asked the group, her rapid-fire cadence picking up as she continued to speak. “I mean, if the man is undetectable, you’re probably not going to get HIV anyway. Why would you take PrEP?”
The question left the room quiet for a minute. But it’s a good point. PrEP is being hailed as the next step in HIV prevention, but research shows that if a man’s viral load is undetectable, the risk of him passing on the virus may approach zero.
At 25, Watson is perhaps the future of HIV prevention. Watson has never known a world without HIV, and for most of her life there have been effective treatments for the virus. To her, the risk of contracting the virus exists, but an HIV diagnosis wouldn’t be devastating, as long as she’s in treatment—which she says she would be. And she fully expects there to be a cure for HIV in her lifetime.
“I don’t want to get HIV,” she told me one day at a café a few blocks from San Francisco General. “But I’m not going to die if I get it.”
Her husband, Deon, has an undetectable viral load, and research shows that when the positive partner’s virus is fully suppressed, there’s very little virus in the system for him to pass on. So when the couple decided they wanted to have a baby, they did—without the assistance of PrEP.
Family HIV Clinic doctor Matin said she’s worked with couples that choose not to use PrEP, and can see it being appropriate—when the positive partner takes his meds so routinely that it’s not an issue and when his health is stable in other ways. For instance, his diabetes is under control, or he hasn’t had a stomach flu that has raised questions about how much of his medications are actually getting into his system. Then there’s the issue of other sexually transmitted infections, which, when present in either of the partners, can increase the risk of HIV transmission.
Finally, while a fully suppressed viral load sounds simple, it can differ between the blood and the semen. “It’s not always clear,” Matin said, “that an undetectable viral load test for blood will translate to reassuringly low levels of risk of sexual transmission of the virus.” That said, results from the PARTNER study of HIV-different couples who had sex without condoms or PrEP suggest an extremely low risk of transmission when the positive partner’s viral load in blood is suppressed.
“As long as we have a good discussion about taking care of both of them, I can imagine a situation where we’d take a pregnancy through without PrEP,” said Martin.
To Watson, PrEP is an unnecessary worry brought about by the fear of the virus—a fear she doesn’t have. So when she found her way to BAPAC, she was already pregnant. The doctors there asked her if she wanted to take PrEP during her pregnancy and explained the risks. Her answer?
“Well, how long has it been tested on pregnant women?” she said. They said it hadn’t been, and explained the slightly smaller birth weight and bone mineral density scores. “Unless they’ve been testing this for years and years out, I’m not willing to do it,” she said. “But it was nice to be offered.”
The couple’s daughter, Valerie, is now a toddler with soft brown eyes and a mop of dark hair. And she and Watson remain HIV negative.
*Hillsborough and Morgan asked that we not use their real names.
Heather Boerner is a San Francisco–based healthcare journalist who specializes in healthcare access and disparities. Her new book, Positively Negative: Love, Pregnancy, and Science’s Surprising Victory Over HIV, follows two HIV-affected couples from first love to first child as they alternately try treatment as prevention and PrEP to keep the women and children HIV-free. Positively Negative is due out later this year.