December 15, 2009
I'm here today with Dr. Antonio Urbina from St. Vincent's Medical Center in New York, where he is director of HIV education. Dr. Urbina, tell me about the new initiative.
We received a grant from the New York State Department of Health to educate every provider in the state on post-exposure prophylaxis [PEP]; this includes how to diagnose acute HIV infection and HIV testing. We had this challenge, and we thought of using widget technology as an efficient way to disseminate this information to physicians. We came up with this AIDS widget.
On the left side of the widget, we have an AIDS clock. In New York State, there is one new HIV transmission every one hour and 50 minutes. We thought that this would be a good way to inform everyone about the impact of HIV -- in particular, here in New York. Every one hour and 50 minutes, you're going to see the clock on the widget advance by one. As of January 1, '09, we've had about 3,400 new HIV transmissions in New York State.
|Antonio E. Urbina, M.D.|
What we did is that with this widget, we put in these video podcasts -- videos instructing physicians what to do in the event of either an occupational -- meaning an actual needle stick -- a non-occupational or a sexual exposure to HIV. We think that this information is vital and that there are gaps in that a lot of physicians either have been outside of their medical training for a long time, or don't really understand what PEP is, how to give it, or that time is of the essence in giving PEP.
Tell me a little bit about when you started working on this.
It was about a year ago. From our original concept to actually having the widget out took about one year. We partnered with this person from Webflow Solutions. He's our IT [information technology] guy and he basically designed the widget. We wrote the scripts. We filmed the videos and we populated the content. What we're most proud of is that we have all of the HIV testing consent forms right there, so people can download them. We feel it's a new form of publishing: It's one-stop shopping, very secure, kind of the anti-Google, anti-Bing way of browsing. You know you're going to get very, very reliable medical information.
Let's talk a little bit about PEP in general. Did you launch this widget to address a gap in emergency room physicians' knowledge regarding providing care for someone who comes in and says, "I might have been exposed to HIV"? Did you find that people were not knowing what to do or how soon to do it?
I think the biggest issue is that doctors and institutions weren't aware that the timely administration of PEP is essential in order for it to work. The animal data show that the earlier one gives PEP, the more likely it is to be effective. If you look at HIV pathogenesis, HIV can go from any type of mucosal surface into the blood in as few as five days. It's really important that the first dose be given immediately.
You also need to know when to give PEP and when not to give PEP. There are certain instances where the risk is really insignificant and there's really no benefit to giving PEP. We're instructing physicians on how and when to give PEP to fill this gap in knowledge.
What's important for PEP is that you give the first dose as soon as possible. If you can't get information about the source patient -- if you think you can, but if more than two hours have elapsed -- the patient should be given the first dose right away. There's very little downside to giving one dose of an antiretroviral regimen. You have to remember that we give these drugs to patients for decades.
How it's believed PEP works is that, if you can prevent the virus from having those initial steps of viral replication, if you can contain the infection locally, then your body can effectively eliminate it. But once it goes to the lymph nodes and starts to replicate and gets into the blood, then you cannot prevent infection. From exposure to HIV getting into the blood may occur in as few as five days, so you really want to get that PEP in as quickly as possible.
If you find subsequently that the source patient is HIV negative, can you discontinue PEP in the patient who was believed to have been exposed?
There's just one caveat: If that source patient is in acute HIV infection, he or she may test antibody negative. What we advise is to only stop PEP if the antibody and the viral load of the source patient are both negative, just to really be secure that there's no potential for HIV exposure. The worst thing to do is if a person was in acute HIV infection and you just tested for antibodies, but they were highly infectious and you told the exposed person to stop PEP.
Now, the PEP regimens can be altered. For example, if that source patient has a multidrug-resistant virus, you might want to alter the PEP regimen to include newer antiretroviral agents like the integrase inhibitors or the second-generation protease inhibitors -- for example, Prezista [darunavir] -- if, in fact, you can determine that that source patient has evidence of a multidrug-resistant virus. We know that those can be transmitted. But again, all of this information you don't have to determine right there. Give the first dose.
We know that there's evidence that just one single agent can be 80 percent effective. We even know that in HIV-positive women that had evidence of AZT [Retrovir, zidovudine] resistance, giving AZT even in those women had a prophylactic effect in further reducing the actual likelihood of transmission. So give the standard first dose and then you can think later and tweak it later. But if you wait, if you delay the initiation of PEP, it can result in transmission.
Can you update this information any time you want, as new guidelines come about? I understand you have guidelines for hepatitis C [hep C] and hepatitis B [hep B] exposure as well.
Yes. What is often forgotten is that oftentimes exposures to HIV can also carry a risk of exposures to hepatitis B or C. Now, both B and C are much more infectious than HIV. If that person that exposed you had hepatitis C or hepatitis B, you are much more likely to get those infections than if they had HIV. It's important to also understand that for hep B there are things that a doctor can do.
Most of us are immunized against hepatitis B, but you definitely want to check to make sure that your titers are adequate. Now for hep C, there is no effective prophylaxis, but what you want to do is manage exposure. That's important because, if you can pick up hepatitis C very early and refer to an expert for treatment, you can be up to 90 percent effective in treating the infection and preventing it from becoming chronic.
For hepatitis C exposure, would it occur mostly through intravenous drug use? Would it also be among MSM [men who have sex with men]?
Absolutely. We think about hepatitis C risk exposure coming from needles -- either intravenous drug use or with actual transfusions before they started screening -- but what we're seeing more, in particular in big urban centers, is increased rates of hepatitis C acquisition through sexual exposure. The vast majority of these cases have involved MSM, or men who have sex with men, where they've been involved with anal sex. Typically it's involved a lot of trauma to the anus and has also been associated with sex toys and the use of drugs, for example, crystal methamphetamine. So you also need to screen patients for sexual exposure to hep C.
Do you have actual guidelines for that? That's something that really needs to be explained to physicians. I think a lot of MSM patients aren't aware that that would be something they should share with someone in an emergency room, if, for example, the sexual exposure included a lot of blood. They wouldn't be aware that this would also put them at risk for hepatitis C or that there are a growing number of gay men in New York that are getting hepatitis C through sexual exposures. If they walked into the emergency room and said, "I had an exposure," they would not be talked to about hepatitis C, but just about HIV.
Again, we have a gap in terms of knowledge. We want to instruct our physicians to consider not just HIV, but in particular hepatitis C, in those high-risk groups. But I think what you'd find, if you were to interview physicians, is that there's a big lack of knowledge about PEP in general, but in particular about hepatitis C exposures.
I understand there's also a phone number that people can call in New York State to get more information.
Yes. There is a 24/7 PEPline number that any New York State medical provider can use. It is out of UCSF [University of California, San Francisco]. It's called the National Clinical Consultation Center. They're basically a think tank for PEP. It's very much operated like an actual Bloomberg newsroom, in that there are these health care professionals that are dedicated to giving guidelines and recommendations for exposure cases that may be a little tricky or where you're having some difficulty deciding whether or not to give PEP.
For example, let's say that there was an exposure risk where the source patient was known HIV positive and had a multidrug-resistant virus. This 24/7 PEPline can help those doctors make the best choices.
Let's talk about the regimen. What are the recommendations right now if someone is exposed to HIV?
There are a couple of guidelines that are out there. I think the two that are most prominent are the CDC [U.S. Centers for Disease Control and Prevention] guidelines and the New York State AIDS Institute guidelines. The New York State AIDS Institute guidelines are a little simpler in that what they recommend is that patients be given PEP if it's indicated, if the exposure occurred within 36 hours. The CDC extends that up to 72 hours, but the point is that the earlier, the better. A lot of people think that they have up to 36 hours or up to 72 hours to make up their minds, but really, there's this golden two hours where it's most effective.
The New York State AIDS Institute guidelines recommend three drugs from the same class, either Combivir [AZT/3TC] with Viread [tenofovir] or Truvada [tenofovir/FTC] with AZT. Now why they include tenofovir is that we know that it gets very good penetration in the genital tract. It's also very well tolerated.
Why they also include AZT is that, if you look at a lot of the data in terms of mother-to-child-transmission studies, most of those studies use AZT. So really, most data comes from AZT, but they wanted to increase the effectiveness of this drug, so they added a third agent. That's basically the combination that they recommend.
The CDC has a more complicated algorithm. They basically divide it up into low risk or high risk. If it's low-risk exposure, what they recommend is just two drugs, either Combivir or Truvada. If it's a higher risk, what they recommend is adding a third agent, either a non-nuke [NNRTI] like Sustiva [efavirenz, Stocrin], or a PI [protease inhibitor] like either Reyataz [atazanavir] or Kaletra [lopinavir/ritonavir]. Those are basically the two guidelines. With our widget, we give the New York State AIDS Institute guidelines of the three nukes [NRTIs].
Is it known which one is more effective, or are they the same?
There's very little data to support PEP. There's really only been one study. It was a CDC study. It was an actual retrospective case-control study. They looked at doctors that were exposed to HIV and they looked at those that were given just one single agent, AZT. What they found was that those that were given AZT had an 80 percent risk reduction in HIV. But that's the only study that's there. The other evidence comes from mother-to-child transmission. We know that in those women that have not had any antiretroviral history, if you give them drugs, you can actually reduce their chance of transmission.
But also in women that have not had any ARVs [antiretrovirals], if the child is given a dose, you can also further reduce the likelihood of transmission. The third line of evidence just comes from animal data, macaques, to know that these drugs can be effective. I'm not sure if the science behind PEP is going to improve much more because now it would be unethical. It'd be very difficult to design a study. First, you couldn't deny somebody PEP because there's enough evidence to show that it works. Second, to look at whether one ARV regimen is better than another would be very, very difficult because in order to actually design the study, you would need such huge sample sizes to show any difference. I just don't think those studies are going to be funded.
How are you publicizing this widget? Are you providing training for people to figure out how to use it?
The CEI Widget offers invaluable access to the latest information in PEP treatment, both Occupational and non-Occupational, along with Pediatric PEP. Screenshot shown is not actual size. Click here to download the widget.
That's our next step, which we have to work on. Right now, our phase one is to get it downloaded into every emergency department throughout New York State.
What we're doing is that we've compiled our e-mail list of all of the emergency departments and we are going to send this widget via e-mail for all of the directors to download onto their desktops. We do want to find some other marketing strategies, so if you any ideas, let me know, Bonnie. [Laughs.]
[Laughs.] Do you think this is a sign of things to come in terms of educating physicians throughout the United States? It's a way to control where the information is being offered. It's a way to always be able to update the information. Are you the first state to do this?
This is definitely the first time that this type of technology has been used for HIV medical education. I think it is a sign of how the use of technology can really assist people in disseminating medical information, in a way that is cost effective and is far reaching. So I do think it's a sign of the future.
I know there are patients who may want to use this kind of widget so they can know what needs to be done, and when they go to the emergency room they can say, "By the way, I did this," or "I did that and I think you have to look at the hep C ramifications of this as well as HIV." Do you think that might be helpful?
Absolutely. Anybody can download this widget. It was really designed for health care providers, but I think for consumers and patients, any type of medical information that they can get can be helpful. I think we're entering a new era of health care as well, where the doctor is not all-knowing anymore. Patients have to take responsibility for their own health and work with health care providers. I think the more information that patients can have, the better outcomes we're going to have.
I know a lot of people come into an emergency room hysterical, very emotional, and they have a low-risk situation. The doctors' question is, "How do we get this person to stop crying? We can't just reject him for treatment. Maybe we should just give him something." Do you have recommendations or do you address this kind of issue?
We do. As part of our training for PEP, there are two things that are very important. One, that it's important to have the information to know when PEP is indicated and when it's not.
When is it indicated?
There are various scenarios that one needs to know. Definitely for a needle stick or for a sharps exposure, if the source is either HIV infected or their HIV status is unknown, then that's an indication for PEP.
For the non-occupational, those are a little more complicated, but for example, for any type of unprotected anal insertive or unprotected receptive intercourse, PEP is indicated. The same thing for unprotected vaginal insertive and also unprotected vaginal receptive intercourse.
For oral sex, it's a little trickier. It's only really indicated if there's been receptive oral intercourse that's gone all the way through to ejaculation.
There are a lot of gray areas, but for example, if a patient comes in and if it's very low risk -- if there's been sperm on intact skin -- that's not an indication for PEP. You need to have the confidence to say, "No, it isn't indicated here," that the risks from these drugs outweigh any benefit.
Now, with any exposure though, it's important to test patients. Just because PEP isn't indicated doesn't mean that you don't test them in a month. For any type of exposure, one should monitor for HIV infection.
A long time ago, the rule was that you had to know the status of your partner. That is a very hard thing for a lot of people who are in these situations: They just had anonymous sex with somebody and the condom broke and they don't even know the person's name. So they have no way of knowing. What's the recommendation?
That's a very good question. The New York State AIDS Institute guidelines have been updated to reflect that, if the source's status is unknown, we assume the worst-case scenario. If the exposure justifies PEP, and if you do not know the status of the source patient, then PEP is indicated.
Now, what's also important is that you test the patient that's been exposed for HIV. One, because PEP is not indicated for people who are already positive, because the meds that we use are really to prevent HIV. They're inadequate for treatment.
That's an important distinction. And now, with the advent of these rapid tests, it's very easy to ascertain the status of that person that's exposed. So that's also an important part of the algorithm -- that you test that person that's exposed because they might already be HIV infected and then they don't need PEP. They need referral to care and possibly treatment for their HIV.
Thank you very much.
This transcript has been lightly edited for clarity.