Dr. David Glidden remembers the lowest moment of his research career. The year was 2012, and he was attending a major HIV conference. Two weeks earlier, the US Food and Drug Administration had approved the antiretroviral drug Truvada for use to prevent HIV infection in uninfected high-risk people (as pre-exposure prophylaxis, or "PrEP.")
One session leader asked an audience of HIV specialists to vote anonymously on a hypothetical scenario: would they prescribe PrEP to an HIV-negative gay man who says he does not and will not use condoms?
"Eighty percent of the audience voted that they would not," said Glidden, a co-investigator in the iPrEx trial, which demonstrated PrEP's efficacy in men who have sex with men (MSM). "I was despondent."
Four years later, many clinicians—including HIV specialists—are not prescribing PrEP. And an emerging body of data suggests that our health care system itself is part of the problem.
PrEP almost seemed like a miracle when it was first approved in 2012: after years of failed efforts to develop an HIV vaccine and other disappointing attempts at developing HIV prevention products, PrEP had nearly 100% efficacy in preventing HIV among drug-adherent MSM and transgender women.
To many scientists and clinicians, PrEP was incredibly promising both as an adjunct to condoms or on its own. While it did not protect against sexually transmitted infections (STIs), it was efficacious, user-controlled, and could be used without a partner's knowledge.
Yet four years later, only a fraction of high-risk patients who would benefit from PrEP are taking it. PrEP is indicated for patients at high risk of acquiring HIV, defined by the CDC as injection drug users, people who are in serodiscordant couples, have sex with people of unknown HIV status, or men who have had sex with men without condoms within the past six months. According to numbers released by Truvada manufacturer Gilead in July 2016, about 80,000 people—less than seven percent of those eligible for PrEP—have filed a prescription in the past four years in America.
Douglas Krakower and Kenneth Mayer, Harvard Medical School researchers who have studied PrEP-prescribing behaviors of clinicians, say one of the biggest reasons for the delay in uptake is that PrEP doesn't fit neatly into any one kind of medical practice. This is partly due to the fact that, until PrEP was introduced, Truvada was generally prescribed only by HIV specialists, as part of HIV infection treatment regimens. General physicians, whom the majority of Americans consult for healthcare needs, were far less experienced with the drug.
Furthermore, HIV and infectious disease specialists are in short supply nationally, with some parts of the country lacking specialists altogether. An analysis by Mathematica Policy Research and the Lewin Group, a healthcare policy research and consulting firm, found that an estimated 1,713 full-time HIV specialists were employed in the United States in 2015; the report estimated that there would need to be 2,215 full-time specialists to satisfy demand for their care. Those already in practice likely do not have the capacity to see the nearly 1.23 million HIV-uninfected Americans whom the Centers for Disease Control and Prevention (CDC) estimates are PrEP-eligible.
The result, said Dr. Krakower, is a "purview paradox": among clinicians he interviewed, "HIV specialists thought it should be the primary responsibility of primary care clinicians... and vice versa: generalists felt HIV specialists would be the better clinicians to do this."
"When you have this paradox," he said, "you have stalled uptake and limited access to PrEP in clinical settings."
But it's not just a lack of ownership that prevents physicians from prescribing PrEP—it may also be a matter of personal judgment. Many in both academic and social circles have raised concerns that taking PrEP might lead to having riskier sex due to a perceived decrease in HIV risk. This "risk compensation," say some PrEP detractors, could lead to other bad outcomes, such as increased rates of sexually transmitted diseases among people taking PrEP.
And while PrEP trials haven't shown evidence of risk compensation, there's some evidence that its spectre is preventing some physicians from prescribing PrEP.
In a study published in the journal AIDS Care earlier this month, 78 percent of HIV specialists said they were very likely to prescribe PrEP to MSM in monogamous relationships, while only 60 to 65 percent were very likely to prescribe it to men who didn't use condoms, didn't know the status of their partner, or had a history of STIs. (The CDC's PrEP guidelines recommend PrEP for all of these groups.)
And in a different analysis of the same data, published in 2015, slightly less than half of surveyed HIV specialists said the risk that a patient may engage in more risky sexual behaviors or may risk acquiring an STI was very important in determining whether to prescribe PrEP.
"Some of these beliefs ... are reminiscent of some of the older beliefs about birth control with women," said Leah Adams, a clinical psychologist at George Mason University and lead author of the study. And similarly, experts argue such beliefs are not a valid reason not to prescribe PrEP.
"We don't say we're not going to give you statins if you're obese and don't watch your diet and you have hyperlipidemia," said Dr. Mayer. "Medical people are quite comfortable accepting the fact that people may make lifestyle choices. If a provider is sufficiently educated in 'real life,' [PrEP] is part of an array of modalities that a sophisticated clinician has to work with."
There are several other potential obstacles to scaling up PrEP, he said. Taking PrEP requires a certain level of self-acceptance related to one's choice of sexual partner. Providers, even those who are well-intentioned, may not be culturally competent during discussions about sex. Some patients are concerned about side effects—Truvada can cause dizziness, vomiting and weight loss, although it is generally well tolerated—or simply unaware that PrEP exists. And despite coverage by some Medicaid programs and private insurance companies—as well as a co-pay assistance program run by Gilead—cost remains a significant barrier to access.
Some are hopeful that PrEP will become logistically easier with the introduction of novel formulations—such as a long-acting injectable drug and rectal antimicrobial gels—but these are years away from being ready for human use. Others are focusing on increasing community awareness of PrEP by engaging users of gay dating apps and popular gay websites.
Although the absolute number of people taking PrEP is low, the trajectory of PrEP uptake – a seven-fold increase in the past four years – is promising to many. And after all, the whole concept of PrEP is still pretty new.
"PrEP today is PrEP 1.0," said Mayer. "In some ways, these are still the early days."
People looking for a PrEP provider in their area can search the PrEP Locator, a national directory of PrEP providers.