A daily pill can prevent the transmission of HIV. Why aren’t we celebrating?
What is PrEP?
Pre-exposure prophylaxis (PrEP) is an oral medication for HIV-negative individuals. Taken consistently once a day, it is extremely effective in preventing infection with HIV. Truvada is the only brand currently available; it’s been FDA-approved since 2012.
How does it work?
Truvada combines tenofovir and emtricitabine, antiretroviral drugs developed to treat HIV/AIDS. It works by blocking an enzyme called reverse transcriptase, which HIV uses to replicate itself.
It was a sunny day three years ago in South Beach, Miami, when John Byrne ’99 tested HIV-positive. He’d been taking a pre-exposure prophylaxis (PrEP) for a year. The drug, Truvada, is known to be miraculously effective at preventing HIV infection, and Byrne was stunned. As he cycled through shame and guilt and fear, his physician ordered a second test. Eventually Byrne learned he’d had a false positive.
The experience, which he wrote about in the Atlantic, didn’t undermine his confidence in PrEP. It spurred him to action. “It helped me understand the emotional and psychological devastation and self-blame, and recognize some of the challenges HIV-positive people have,” Byrne says. “After that, I became aware that there was really no marketing for PrEP in Miami.” He took it upon himself to launch a nonprofit campaign, Prevention305.
Southern states have been hit disproportionately hard by HIV, and “The 305” (Miami’s area code-inspired nickname) sees new HIV infections at an annual rate of 47 per 100,000 residents — three times the national average and more than any other U.S. city, according to the Centers for Disease Control and Prevention. Florida alone accounts for 10 percent of HIV cases in the U.S., and more HIV infections progress to AIDS there than in any other state. The diversity of the state’s residents also means prevention campaigns struggle to reach across urban and rural divides, as well as those of race, ethnicity, gender identity, and sexuality.
Although the U.S. Food and Drug Administration approved PrEP for high-risk populations in 2012 and it’s been a central prong of HIV-reduction campaigns from San Francisco to New York State, the little blue pill is not reaching the majority of Americans, especially people of color, who could benefit from it most. In the U.S, young gay black men have an almost 50 percent chance of contracting HIV in their lifetimes; gay Latino men have an almost 1 in 3 chance. By the CDC’s estimate, two-thirds of those at high risk are African American or Latinx, but they account for the smallest percentage of prescriptions to date.
Prevention305 targets Latinx immigrants and transgender women in Miami, where around 60 percent of the population is foreign-born and, as Byrne says, in South Beach alone “the HIV rate exceeds that of sub-Saharan Africa.” Byrne, publisher of the news site Raw Story, began underwriting the campaign in 2015. Now funded by Gilead Sciences, the biopharmaceutical company that manufactures Truvada, and AIDS United, Prevention305 has a remote staff of six. With no office, there’s low overhead. “It’s a way to do more with less,” Byrne says.
“A lot of our work is teaching people that they can get PrEP wtihout insurance. The health care system is daunting, and it’s doubly so if you didn’t grow up in the U.S.”As awareness of PrEP has increased among higher-risk populations, Prevention305 has focused on education and access. “Peer navigators” triage for clients, make appointments, and arrange transportation to federally qualified treatment centers where the uninsured (about 20 percent of Floridians) can get PrEP for free. For those with higher incomes, insurance foots the bill.
– John Byrne ’99
“The cost of the drug is more of a psychological hurdle,” Byrne says. “Some people have it in their heads that it’s expensive and rule it out. So a lot of our work is teaching people that they can get it without insurance. The health care system is daunting, and it’s doubly so if you didn’t grow up in the U.S. Even legal permanent residents are worried that they’ll test positive for HIV and be deported.”
Prevention305 partners with the Miami-Dade Department of Health, the University of Miami, and Miami Beach, whose city commissioners designated $250,000 to establish a mobile PrEP clinic. Outreach has expanded from posters and brochures to dating apps and social media, and Byrne says Instagram has been a surprisingly robust source of referrals.
Nationwide, according to Gilead, approximately 163,000 people are taking Truvada — nowhere near the 1.1 million the CDC estimates are at highest risk. In Miami, around 1,500 people are currently on PrEP, Byrne says. In the past six months, Prevention305 has helped around 140 start treatment.
A Hard Pill to Swallow?
Truvada combines two antiretroviral (ARV) medications, tenofovir and emtricitabine, long used in treating HIV; it works by preventing the virus from replicating in the body. For people with normal kidney function, PrEP’s side effects of nausea, headaches, and weight loss are generally uncommon, minor, and short-lived.
Clinical trials demonstrate that Truvada is more than 90 percent effective in preventing HIV-negative individuals from sexually acquiring HIV. Studies that monitored usage suggest that when taken correctly — every day, without fail — its efficacy could be as high as 99 percent. Inconsistent dosing lowers protection. For IV drug users, the figure is closer to 70 percent.
In his career in global public health, Adil Bahalim ’02 has supported community health following the Ebola crisis in Liberia, developed strategy for the Global Fund to Fight AIDS, Tuberculosis and Malaria, and consulted for the HIV/AIDS department of the World Health Organization. Now he is finishing a doctoral program in public health at Harvard University and directing business development for UrSure, a Cambridge, Mass., startup that has introduced a tool for improving PrEP adherence. The noninvasive diagnostic test measures the tenofovir in a patient’s urine and identifies individuals who need more support to ensure that they take the pill as prescribed.
A major challenge is patients “not understanding how the disease and the drug work, or the importance of staying on it,” Bahalim says. As well as providing an objective measure of adherence, the test reassures patients, who might not feel different when taking the medication, that they’re protected.
“There are hurdles from distrust and poor healthcare literacy that need to be overcome through better PrEP education and support,” says UrSure co-founder Giffin Daughtridge. “Without peace of mind that the drug is in their system and protecting them, many people don’t have enough motivation to take it consistently.”
Irregular use is not a minor concern. Daughtridge is a physician, as is the company’s other co-founder, who ran a clinic that continued to see patients contract HIV while using PrEP haphazardly. UrSure is betting that by making adherence easier, it can help realize PrEP’s promise of near-perfect efficacy.
Currently, UrSure’s test requires analysis in a partner laboratory with a three-day turnaround. Within the next year, Daughtridge expects to roll out a point-of-care test, similar to a pregnancy dipstick. “Our goal,” he says, “is to show results right in the doctor’s office, so discussions can happen immediately with patients who need more extensive adherence tools.”
UrSure has raised around $2 million from small-business innovation research grants from the National Institutes of Health, startup incubators, and Harvard University innovation challenges. It’s focused on the U.S. market but is assessing the feasibility of expanding into international settings. UrSure is also piloting marketing to individuals for home-based tests and developing a smartphone scanner so that patients can upload and relay results to their physicians in real time.
HIV in the U.S.
In 2016, there were1.8million new cases of HIV worldwide;
nearly40,000of them were in the United States.
More than1.1million people in the U.S. are living with HIV today;
1 in 7of them don’t know it.
Southern states account for38%of the U.S. population
but over50%of new HIV diagnoses.
Controversy and Its Costs
Historically, PrEP’s loudest critic has been Michael Weinstein, founder and director of the AIDS Healthcare Foundation (AHF), the largest and most controversial AIDS organization in the world. He has taken an unorthodox position in decrying PrEP as a “party drug” that will lead to a decline in condom use and a catastrophic surge in risky sex, and in lobbying against measures to mandate PrEP education.
“A major challenge is patients not understanding how the disease and the drug work, or the importance of staying on it.”More recently, AHF has softened its stance on PrEP and has created a walk-in PrEP clinic in partnership with Broward County, Fla. However, the Prevention305 staff still contends with the consequences of this campaign. “Weinstein runs the biggest HIV testing center in southern Florida,” Byrne says, “but they won’t necessarily mention PrEP during HIV testing, even to those who admit to inconsistent condom use.” Prevention305 steers people to centers where they’ll be thoroughly counseled.
– Adil Bahalim ’02
Though they have long been the gold standard in HIV prevention, condoms aren’t foolproof. According to the CDC, 68 percent of HIV infections occur among men who have sex with other men. When used correctly, condoms reduce their risk of acquiring HIV by around 70 percent — that’s highly effective, but less than what’s possible on Truvada.
The CDC is clear that using condoms along with PrEP provides greater protection — it’s not a zero-sum game. But PrEP might have the advantage of meeting many who shun condoms where they are.
Byrne says it’s time to acknowledge reality. “In my experience, no one is using them,” he says. “We don’t expect straight people to, especially in monogamous relationships. And, because of the politics of the AIDS epidemic, there’s a question tied up in that double standard of whether gay people are entitled to intimacy.”
For Byrne, the fact that gay men on PrEP have stopped having to ask their partners about HIV status is a giant step toward ending the stigma associated with HIV.
“In Miami, people are still dying of AIDS,” he says, “but to say we’re not going to deploy an intervention that will prevent that because some people are being irresponsible, that’s not good public health.”
A recent review in the journal Clinical Infectious Diseases suggests that PrEP could be contributing to increased rates of other sexually transmitted diseases. It’s true they’ve been on the rise, but because the PrEP treatment protocol includes testing every three months, it’s also possible that infections are simply being caught earlier. Regardless, UrSure’s Daughtridge says their impact can’t be equated with that of HIV.
“HIV is a chronic, lifelong infection that costs $500,000 to $1 million per patient over a lifetime to manage,” he says. “Many other STDs are not very difficult to treat. If there’s a choice to be made, we should choose to prevent HIV.”
“When I was at the WHO in 2011, we weren’t yet sure about PrEP, if it would be as effective as early trials promised it might be,” Bahalim says. Now, he says, the benefits are clear: “This is as close as we can get to a vaccine. It’s absurd for anyone at high risk not to use PrEP.”
Concerns about adherence may eventually be addressed by other medical advances. Long-acting forms of PrEP — injections, implants, vaginal rings — are being developed. And because transmission in the United States is largely confined to specific demographic groups, efforts that focus on high-risk populations have the potential for outsized impact.
At Prevention305, the staff reflects the demographic it serves: Latinx, immigrant, under 35. Byrne intends to one day hand over the reins. “I’m not of the target population,” he says, “and people assess the legitimacy of an organization based on whether they see people like them leading it.”
He hopes to begin reaching out to Miami’s African American community, but he recognizes that a new targeted approach has to be an independent program. “Cultural literacy is crucial,” he says.
Wendy Arnold ’65 has been facilitating peer-to-peer efforts at preventing HIV since the AIDS crisis began. While working at the AIDS Project of Los Angeles in the mid-1980s, she was recruited to start a prevention program for teens in France. “The most effective strategy was teen-to-teen,” Arnold says, “to break down intergenerational barriers of communication around the sensitive subjects of sex, relationships, body, and health.”
She stayed for six months, starting L’Association “Jeunes” Contre le SIDA (Youth Against AIDS), then began similar programs in countries in Eurasia, Africa, and the Americas. In 1990, she founded the Peer Education Program of Los Angeles (PEP/LA), which runs 25 satellite programs in Southern California. PEP/LA and PEP/International have a dual mission: to slow the rate of HIV transmission in adolescents and to increase compassionate care, hope, and respect for people living with HIV/AIDS.
In 28 countries, Arnold has run two-week training sessions for teens and, separately, for diverse groups of adults — clergy, sex workers, medical professionals, nonprofit directors, prison staff. During her trips, she stays with local residents, sometimes in remote rural villages, sleeping on mats with women in Uganda, helping write grant proposals in Vladivostok, or connecting a group in Kathmandu with international funding. She respects cultural, ethnic, and economic differences, and she praises her trainees for successes: “These programs work because they get credit for running them.” Arnold stays in touch and returns when communities want to organize additional training programs.
“Over the last 10 years, we’ve made a lot of progress dialoguing about embarrassing and taboo subjects, both locally and internationally,” she says. “When teens talk honestly and openly about risk-taking behaviors, it reduces the number of them getting infected.”
Arnold is cautiously optimistic about the fight against HIV/AIDS, particularly recent strides in reducing maternal-infant transmission. In cultures that won’t consider barrier methods of contraception, she works to influence social norms — encouraging personal protection, self-respect and respect for partners, honesty, and faithfulness. “You can’t go against the culture as an outsider,” she says. “You have to work with locals, within the culture.”
As HIV has become more manageable, Arnold has noticed that young people are no longer as concerned about acquiring AIDS. “I find that extremely worrisome,” she says. “They think they can just take the ARVs and it wouldn’t be a big problem.” The treatment regimen no longer requires dozens of daily pills, but they still have side effects, missing doses can lead to drug resistance, and the medication can be expensive without health insurance.
Arnold sees some clear benefits of PrEP. “It can be incredibly liberating for couples with mixed HIV status,” she says, affording them “relief and optimism.” But she thinks most people aren’t taking sufficient precautions. “Without condoms, Truvada can give a false sense of security,” she says.
She is especially concerned about intravenous drug users, among whom HIV infections are surging. “Drugs make people take everything they’ve learned and throw it out the window,” she says. “They’re the bane of AIDS education.”
In many developing countries, particularly in rural communities and other areas where she still encounters fundamental misunderstandings about how the virus is spread, Arnold also sees barriers to PrEP’s usefulness — of cost, transportation, accountability, and communication. “It’s very complex,” she says. “There’s no simple solution.”