PrEP for the Next Generation

Pioneering Fenway Health leads HIV prevention care and research 

Fenway Health's Ansin Building, 1340 Boylston Street. Image: Fenway Health

Fenway Health's Ansin Building, 1340 Boylston Street. Image: Fenway Health

In ways that once seemed unimaginable, HIV-infected people have a great deal more to be optimistic about today than when AIDS first surfaced more than 30 years ago.

The virus is known. So is the way it is transmitted. There is a test. There is treatment.

There is no vaccine or cure—yet—but now there is another approach to prevent HIV transmission. Called pre-exposure prophylaxis, or PrEP for short, it involves giving people at high risk of infection one or more antiretroviral drugs from a combination that has transformed an HIV diagnosis from a death sentence to a chronic disease.

PrEP has helped prevent the spread of infection, but Kenneth Mayer believes more progress can be made. The Harvard Medical School professor of medicine at Beth Israel Deaconess Medical Center is troubled by missed opportunities. He would like to see more people taking PrEP to prevent further infections.Kenneth Mayer

“We have 50,000 new infections a year in the United States. That number has gone down from the height of the epidemic, but it’s been on a slow decline for more than a decade,” said Mayer, medical research director of The Fenway Institute, the research, training and health policy division of Fenway Health, the largest ambulatory facility caring for HIV-infected patients and sexual and gender minority patients in New England.

“Part of the reason why we continue to have new infections is we have a core group of people—between 150,000 and 200,000 people—who have the virus and are walking around unaware, and an even larger group of people—around half a million—who were diagnosed with HIV, who are not fully engaged in care, and whose HIV infection is not optimally suppressed with currently available drugs,” he said.

“One of the great things about Fenway is we’re not at the bench, but we can identify clinical research questions that can be taken promptly to the bench and do ambulatory clinical trials, moving seamlessly from the bedside into the community.”—Kenneth Mayer

Mayer’s mission is “next-generation PrEP,” which means reaching people who may not know whether they are infected and, if they are not, assessing their risk of acquiring HIV and offering them the chance to reduce their risk.

Taking a pill once a day has been proven safe in clinical trials dating back to 2010, including the first PrEP trials in the United States, which were conducted by Fenway Health.

Long Road

The Fenway Health organization has long been a pioneer in HIV treatment and research. Its roots in community health date to its federal certification as a community health center in 1971. It also fosters research in The Fenway Institute, which is housed in the same glass tower on Boylston Street not far from its early home in the neighborhood.

Mayer was there for the first wave of the epidemic, during his infectious diseases fellowship at Brigham and Women’s Hospital. He worked in a clinic that was part of Fenway Community Health Center, treating sexually transmitted diseases. Men and women were dying of AIDS before the syndrome had a name, and the virus was spreading unchecked. Fear filled their days.

The sickest patients went to hospitals where their best hope was to get treatment for opportunistic infections. Those who were not sick asked Mayer and others at Fenway about their partners who were stricken: Can I bathe him? Can I kiss him? What should we do with the bed linens?

Answers were few then, but Mayer’s fruitful collaboration with Jerome Groopman at New England Deaconess Hospital (before it became part of Beth Israel Deaconess) was an example of the kinds of successful partnerships Fenway has had with Harvard-affiliated hospitals.

In addition to its collaboration with Beth Israel Deaconess, Fenway counts among other partners Brigham and Women’s Hospital; Massachusetts General Hospital; the Ragon Institute of MGH, MIT and Harvard; and the Harvard T.H. Chan School of Public Health. Groopman is now the HMS Dina and Raphael Recanati Professor of Medicine at Beth Israel Deaconess.

In the epidemic’s early days, Mayer noticed that not all patients who had infected partners became sick. In a study funded by the Massachusetts Department of Public Health, he began collecting blood samples from the uninfected partners. At Beth Israel, Groopman was seeing sick patients with Kaposi’s sarcoma, a previously rare cancer that people with AIDS were developing because compromised immune systems left them defenseless.

Mayor recalls Groopman calling him when it appeared that Robert Gallo, who was at the National Cancer Institute, had isolated the HIV organism and had devised an antibody test. Groopman and Mayer gathered their samples for a double-blinded, independent panel to test.

This early natural history study revealed valuable information about how the disease was transmitted. It also brought disheartening news. Antibodies to HIV almost inevitably meant eventual disease progression for the vast majority of people who harbored them, as opposed to the protection that some antibodies, such as antibodies to the surface of the hepatitis B virus, provide.

That legacy of collaborative research helped Fenway develop as an “academic community health center,” with Mayer and many others on the front lines of the epidemic, both seeing patients and seeking basic science answers. Their focus continues today.

Beyond the Bedside

“One of the great things about Fenway is we’re not at the bench, but we can identify clinical research questions that can be taken promptly to the bench and do ambulatory clinical trials, moving seamlessly from the bedside into the community,” he said.

Fenway currently cares for more than 2,000 people living with HIV in Southern New England, but there are more than twice that number who are at high risk and are engaged in primary care at Fenway Health. Uninfected men who have sex with infected men are the largest population at risk, followed by intravenous drug users, as well as men and women who have heterosexual sex.

“In addition to having an HIV primary care specialty practice, we see a lot of people who have a vested interest in not becoming infected,” Mayer said. “It seems like a natural focus of our research interest.”

Fenway was one of two sites to participate in the first clinical trials of PrEP. Animal models had shown that taking two of the several drugs used in a combination that keeps HIV at bay can also prevent infection, rather than just treat it. Testing in humans faced a high bar, as do any trials in otherwise healthy people, but it was successful.

Fears of increases in unprotected sex or other risky behaviors have not materialized, Mayer said. Although the people who take PrEP tend to maintain their levels of condomless sex, they don’t usually become HIV infected because most are adherent to the medication regimen. Multiple studies have shown that PrEP reduces the risk of HIV infection by more than 90 percent among high-risk, adherent patients.

The U.S. Food and Drug Administration approved a PrEP drug combining tenofovir and emtricitabine, better known as Truvada, in 2012. In September 2015, the World Health Organization endorsed daily oral PrEP as an additional method of prevention for those at substantial risk of contracting HIV, echoing a similar stand taken by the U.S. Centers for Disease Control and Prevention in 2014.

Treatment with PrEP, which costs about $15,000 a year (including clinical monitoring), is covered by most insurance companies and by public insurance plans in many states. Researchers are working on ways to offer PrEP as not just a daily pill, Mayer said, but perhaps through injections every two months as an alternative. Further refinements could include gels, intravaginal rings or other devices for women at risk.

Educating Patients and Providers

PrEP is not a panacea, Mayer hastens to add, but he said it holds great promise as part of a holistic package that Fenway and other clinics can offer patients.

“PrEP is only going to be effective if it is concordant with people’s lifestyles and their life circumstances,” Mayer said. “So PrEP needs to be embedded in a larger conversation about sexual health.”

Educating primary care providers is another avenue to explore. Mayer’s colleagues at Harvard-affiliated hospitals are working with providers to help them talk to patients about high-risk sex.

Harvey Makadon, HMS professor of medicine at Beth Israel Deaconess and director of training and professional education at The Fenway Institute, has received grants to train primary care providers in the new prevention paradigm. Douglas Krakower, HMS instructor in medicine at Beth Israel Deaconess, received a National Institutes of Health grant to study how to best train providers to be more effective in their HIV prevention counseling.

With state and federal funding, Fenway is investing in community education in the hope of eliminating barriers to care, including medical mistrust. The HIV epidemic is disproportionately concentrated among people of color, particularly black Americans, Mayer emphasized. Colleagues throughout Harvard are reaching out to underserved groups across Boston and around the globe, including India, Peru and South Africa.

Pragmatic deployment of PrEP is needed, Mayer said, to move past the plateau of new infections.

“The time for cautionary speculation is over,” he wrote in a commentary published by The Lancet in September 2015. “HIV prevention services should be expanded worldwide by offering PrEP routinely to those who could benefit.”

Fenway Health, Mayer said, is proud to be part of that push.

“A vaccine or cure are the holy grail, but they are not the bird in the hand that PrEP is.”