September 28, 2012
In July 2012, the U.S. Food and Drug Administration (FDA) approved, for the first time, an antiretroviral drug for the prevention of HIV. To be specific, the FDA approved the fixed-dose combination pill tenofovir/emtricitabine (Truvada). The drug has existed for years as an HIV treatment option, but the FDA's action this past summer made it the first drug approved for HIV pre-exposure prophylaxis, or PrEP for short.
As we prepare for the introduction of PrEP into clinical settings throughout the U.S., there are understandably a huge number of questions. To address many of these questions and obtain guidance for health care professionals across the clinical spectrum on how to prepare for and adjust to the rollout of PrEP, I spoke by phone with Antonio E. Urbina, M.D., the associate medical director at St. Luke's and Roosevelt Hospital's Center for Comprehensive Care's West 17th Street Clinic in New York City. Prior to that, Urbina was, for many years, the medical director of education and training at St. Vincent's Comprehensive HIV Center.
Months of conjecture and debate have taken place regarding the use of HIV pre-exposure prophylaxis, or PrEP. Now we're finally at the point where PrEP is ready to be used in clinical situations. What do we know so far about the basics of when and how to use it?
One thing is very clear from the data. Not just animal data -- which was the first data that showed that, if you give uninfected animals the same drugs that we give to people who are HIV positive, and then you expose them to strains of SIV, which are very similar to HIV, you can prevent infection in these animals. That data has been available for a long time.
Now we've got multiple studies -- not just the iPrEx study, but a lot of other studies -- that have unequivocally shown that pre-exposure prophylaxis is effective when it's given to high-risk individuals. So the science is there. I think a lot of us are overjoyed that, finally, the scientific community and the political will are there to prevent new infections from occurring.
You mention high risk. Let's get into the details a little bit, as far as the proper use of PrEP as we move forward. What constitutes high risk?
Ultimately, it's a subjective question; it's a continuum. Not everybody is always at high risk at every point in their life. They go in and out of risky behavior.
But if we're starting to evaluate persons for PrEP, we do want to give it appropriately to people who are at high risk. Generally how that's defined is: persons who knowingly engage with others who are known to be HIV positive. That's one definition.
Another one is: persons who engage in sexual activity in an area that has a high prevalence of HIV, and who also have inconsistent or no condom use.
There are also people who are coming to your office or clinic with multiple sexually transmitted infections. I think that would categorize another person that may be a potential candidate for PrEP.
Then there are other kinds of high-risk behavior: anyone who exchanges sex for other commodities, such as money, shelter, food or drugs; persons who are substance users; persons who were recently incarcerated.
Again, it's a really subjective call: anyone who's HIV negative that you feel is putting themselves at risk. I think any of those could be candidates for PrEP.
A lot of the risk factors that you just outlined get into some pretty sensitive issues that I think many people within the health care field might be a little bit wary of bringing up with a patient. Topics such as sex and drugs, even within the clinical field, tend to be not easily broachable with patients. If part of the process of determining whether to offer PrEP to a patient consists of making that kind of analysis or examination of their sexual -- and, perhaps, drug use -- risks, how does a health care provider navigate that?
Medical training doesn't really provide a good background for health care providers speaking with patients about these kinds of sensitive issues. For some, it's always going to be very difficult for them to interview patients and have a dialogue about risky behavior.
Before, it was just risk-reduction counseling and safer sex; distributing condoms. But now, with PrEP, we have an additional tool, a chemoprophylaxis agent that could be given to patients. In order to determine if a patient is eligible, you really are going to have to have these difficult and often-sensitive questions, or questions that may be embarrassing to the patient.
What it really boils down to is trust. It's trust between you the individual provider and the patient who's sitting opposite you. All of us are really going to have to break down those barriers and say, "In order for me to prescribe something that I think may benefit you, may actually prevent you from acquiring HIV, we're going to have to sit down and talk about what may be some difficult issues. And I want you to be as honest with me as you can."
Now, I think you can phrase things in a way that may normalize behavior. So, for example, instead of saying, "Do you use drugs?" or something like that, which kind of already has a negative connotation, what I'd typically tend to do would be to say, "Do you find it difficult, on the weekends when you go out, not to use?"
It is important how you frame the question, how you start to get a history, so that you can put patients at ease, make them comfortable and, I think most importantly, let them know that you're not judging their behavior. But, again, that's a difficult task, and there are going to be some people who are better at it than others.
I don't always think that it has to be the provider; I think it can be anyone on the health care team who can approach the patient. I'm very much in favor of using people who are more skilled, who have that level of emotional intelligence that can connect to patients and elicit that information -- sexual history, drug-using history, things like that. Sometimes that could be a nurse, a social worker, a patient navigator, etc.
To what extent does the burden fall on the patient, or the client, to request PrEP? How much information can any health care provider just make generally available -- like in a waiting room or within the office -- to let patients know that PrEP exists, versus waiting for patients to find out about it themselves and then come in saying, "I've heard about this; can I try it?"
Already now, we are having patients coming in and saying, "A friend of mine told me about something that I can take." Or often it's somebody who's already infected [and doesn't yet know it] who will come and say, "I heard that there's possibly something that I can take."
I think information is power. I think having things in the waiting room that explain what PrEP is -- even something that simply says "Did you know?" and then lists out what it is, how it's prescribed, etc. -- I think that's a useful tool. And information about PrEP would really benefit anyone.
We want to get that dialogue started, because even if a patient isn't an ideal candidate for PrEP, or let's just say that after you offer them PrEP that they decide to say no, it's still an opportunity to engage them in a conversation about HIV, about actually reducing their risk, about getting HIV tested, about being screened for sexually transmitted infections. It's just a great opportunity. And PrEP can be the catalyst for it.
Do any of those waiting room materials that you just referred to exist yet?
No. In the offices and the clinics that I've been to, I haven't seen anything yet out there giving information about PrEP.
Are there people for whom you definitely would not want to offer PrEP?
I would say yes. The data with PrEP shows that adherence is key. PrEP needs to be taken daily in order for it to be most effective. That information needs to be parlayed to patients very clearly, because you don't want people thinking that they can intermittently take PrEP and it's going to be effective. You have to make sure that the patient understands the science and understands the data that shows you have to have a high level of adherence in order for PrEP to be effective.
I would say that, if a patient could not commit to taking the tablet daily, then that patient would not be a good candidate for PrEP.
Are there any red flags that would indicate that?
Before starting someone on PrEP, I would form an agreement with that patient that they would follow my recommendations.
The recommendations include that they get frequent HIV testing. PrEP is indicated for persons who are HIV negative, obviously. Studies show that in people who had very early infection, but whose infection was not picked up, and who were started on PrEP, in some of those patients, not only did it not work, but they actually developed resistance to those medications.
So, if a patient can't commit to coming in, getting a baseline HIV test, and also getting frequent HIV testing -- in the studies, a lot of them did monthly HIV tests, but the guidance says at least every two to three months -- if a patient can't commit to coming in and being monitored, I think that that would be a red flag.
I would clearly state all of the agreements that I think would be essential before I actually prescribed someone with PrEP. Because PrEP, if it's not monitored, could be potentially hazardous: These are medications that we give to patients with HIV; they have potential toxicities that, if they're not picked up early, can have really bad outcomes.
So, again, I would clearly state: "I will need to see you at least every three months to check in, monitor adherence, do an HIV test, monitor some of your labs." PrEP is not something where you can write a prescription and have 11 refills. That's where I think really we can get ourselves into some pretty serious problems.
What about clinical reasons to potentially not prescribe PrEP?
The great thing about the HIV scientific community is the miraculous work that they've done with drug discovery and development. The lifespan of those with HIV now approximates those that are HIV negative. I have a patient who's 86 years old. And the most recent data from a large cohort trial, the D:A:D study, found that there's no real signal for any major toxicity from antiretroviral agents. If you look at the big causes of death, it's non-AIDS-associated malignancies, non-AIDS infections, and cardiovascular and liver complications. But there's not a big signal from really any of the antiretrovirals.
It doesn't mean that they cannot potentially cause adverse events; and we know those. Truvada itself, if you're looking at patients' adverse reactions: They were mild. Only a couple of symptoms occurred with more frequency in those who were prescribed Truvada. Those were headache, a little bit of abdominal pain and some weight loss.
But some of the more potentially serious side effects could include some issues with the kidneys. So far, the data haven't shown any alarming trends, just a little signal of some abnormalities with kidney function. All of those normalized with discontinuation of Truvada.
Another potential clinical side effect is some bone mineral density [BMD] loss, or what's called osteopenia. But again, that has been mild and typically reversible with discontinuation of the medications.