Terri Wilder: The New York State Department of Health AIDS Institute Clinical Guidelines Program has been in the forefront of clinical guidelines, sometimes even releasing their guidelines before the Centers for Disease Control and Prevention [CDC]. Can you talk about why there is a need to release a new edition of the PEP guideline?
Elliot DeHaan: The 2020 updated guidelines approach post-exposure prophylaxis, i.e., PEP, with a core algorithm to follow, with additional guidance for scenarios of specific matters in occupational post-exposure prophylaxis [and] non-occupational PEP, which includes consensual sexual exposure and exposure through needle-sharing, sexual assault, and exposures in children.
We took this approach because we felt there were more similarities than differences in each of these four types of post-exposure prophylaxis. Having one document for medical providers to refer to makes it more user-friendly and accommodates scenarios that may cross, so to speak, types of exposures—such as a needle-stick in the community, at a park, or at home, etc.
We also wanted to update the guideline to stress the urgency in initiating PEP, particularly the first dose of PEP. There will be a lot more on that later.
We also wanted to address some specific matters that have changed since the last guideline update—which include an increase in the use of PrEP in the community (which is a really great thing) and the U=U [undetectable equals untransmittable] statement put out by the state and local New York City departments of health.
Our final goal was to create a user-friendly guideline that is both comprehensive and easy to access. The online format allows for medical providers to quickly access sections that are relevant to their particular situation. It includes helpful information and links on legal matters related to PEP, as well as practical considerations, such as payment [for] medications and starter packs.
TW: It’s a very thorough document. I’m just curious: How long did it take you and the committee members to work on this before it was released?
EDH: We put in a lot of time and effort into these guidelines over a three-year period. There was a lot of input from clinicians all over the state. But also, there was input from members of the community, legal experts, and public health officials, as well. So, it was a very diverse group of people.
TW: In the past, the New York State Department of Health AIDS Institute PEP Guideline recommended that initiation of PEP be within 36 hours. And I notice that in this iteration it’s been changed to 72 hours, ideally within two hours of exposure. Can you talk about why the document has changed from 36 hours to 72 hours?
EDH: That’s a very good question. We had a lot of discussion about this change, and our position ended up being that, while efficacy in animal models drops after the 36-hour time point, it doesn’t go down to zero. And so we felt that even within the 36- to 72-hour window, PEP may have a significant difference in preventing HIV infection. So, in other words, just because the efficacy starts dropping, it doesn’t mean you should withhold the treatment.
After 72 hours, there’s really no evidence that PEP is effective, and, in fact, there’s evidence that after 72 hours, infection is established. And then we’re addressing a different issue; instead of prevention, we’re addressing treatment of acute HIV infection.
So, we felt good about having a hard, fast line on 72 hours at this point.
Another benefit of changing to the 72-hour cutoff is that it aligns our state guidelines with the CDC guidelines. In many instances, clinicians were confused by the different cutoffs, and why different guidelines were using different hourly cutoffs. In the old New York State guidelines, anything after 36 hours used to be considered on a case-by-case basis. Now we are allowing up to 72 hours. But I want to stress, it’s really as soon as possible—ideally within two hours; no later than 72 hours. So we really want to stress that you want to give the first dose as soon as possible.
TW: Can you tell me about the guidelines regarding the provision of the full course of PEP medications, whenever possible? So, basically, giving the entire 28-day regimen to the patient.
EDH: Ideally, this would be the best-case scenario—that you could give the full 28 days. This way, you don’t have to worry about problems obtaining the remaining doses of a 28-day course. However, this can be, and often is, cost-prohibitive in most settings, and in most medical institutions.
So, alternatively, we have recommended a seven-day starter pack if you cannot provide the full 28-day course. Alternatively, ERs and PEP clinics have tried seven-day starter packs and given scripts to patients for the remaining three weeks of treatment. This has challenges of its own, since in these occasions the medical providers need a system to store and track the seven-day starter packs.
However, it’s not an insurmountable problem. And there are many PEP centers in New York City and in New York State that have the ability to give a seven-day starter pack and have had success storing the medications and logging them and, you know, keeping track of them.
TW: There is a lot of information specifically for victims of sexual assault. Are there any key considerations regarding PEP for victims of sexual assault, in terms of the provision of the course of the PEP medications?
EDH: Yes. One key consideration is the provision of PEP medications in the form of starter packs. New York State law requires that you provide a seven-day course if an individual is 18 years or older and is the victim of sexual assault. And if they are under the age of 18 years old, the person should receive the full 28-day course. So, this is New York State law. This isn’t just a recommendation; it’s actually the law. And you have to abide by that in New York State.
Other considerations are the need for empiric STI treatment up front. This is a little bit different than sexual exposure that is consensual. In the case of sexual assault, we treat empirically for gonorrhea, chlamydia, and trich. We do not necessarily do what’s called baseline testing for STIs.
Now, you may ask, why is that? Well, unfortunately, there have been situations where baseline testing for STIs has been used to bias a jury in cases of sexual assault. So, this risk could even be shared with the person, with the patient, prior to obtaining the baseline testing. In that case, the patient may decide not to get the baseline testing. And that’s understandable. In either scenario—if they accept or reject the baseline testing—they need to be treated empirically for sexually transmitted infections.
TW: When you say, “bias the jury,” the lawyers, essentially, may paint the victim as a person who has multiple sex partners—“See, they have an STI; this probably was consensual. They just don’t want to admit it”—is that what you’re saying?
EDH: Exactly. Yes. It has been an issue. And because of that, we want to be accommodating for the request to have baseline testing but, at the same time, have the patient make an informed decision, knowing that risk that is involved.
TW: So, if the victim of sexual assault is not tested for an STI, but they’re presumptively treated for it, would documentation of the treatment bias the jury, as well? Or is it something that could be justified—like, “Oh, we do this with all our sexual assault victims, no matter who they are”?
EDH: Yeah. I would say the latter. It’s kind of justified by protocol, so that this way no one can use that result. There’s no result to bias a jury.
TW: I was just curious about the justification between the sexual assault victim being less than 18 and getting the full course, versus the person who’s over 18 and a victim of sexual assault and getting a minimum requirement of a starter pack. How was that decision determined, do you know?
EDH: I don’t know exactly. I think it’s the law. I would refer you to the links on the guidelines that can talk more in depth about the law. How they arrived at that, I believe, had to do with issues of consent and also perhaps access to medications, being that individuals who are under the age of 18, there is a high risk that they need to have access to the full 28 days because of issues of informing parents, etc. I don’t know the exact history as to why that was used. But I believe that those were some of the concerns that the lawmakers had.
TW: OK. I also notice that the document has some guidelines regarding pediatric populations and PEP, which we’re kind of talking about right now. But can you tell me a little bit more about the pediatric populations and PEP? It looks like it’s still kind of framed around sexual abuse.
EDH: Yeah. So, the pediatric portions of our guidelines address important considerations, such as dosing—particularly that we use the cutoff of 40 kg for the PEP medications. It also addresses the legal issues involving the capacity of minors to consent to treatment and prevention services for sexually transmitted diseases.
There are provisions in Article 2305 that require the Commissioner of Health to promulgate a list of sexually transmitted diseases. There was an amendment to this article in 2017 that added HIV to the list of STDs. This was a really important issue, because it brought the capacity of minors to consent to HIV treatment and HIV prevention services on par with that for other STDs.
Another provision of Article 2305: Medical or billing records may not be released or made available to the parent or guardian, without the minor patient’s permission.
TW: Got it. There is an interesting section in the guideline on PEP for a person taking PrEP. And I don’t think I’ve ever seen much written or talked about on this topic. You know, it’s possible I missed it. But it’s interesting. So, a person is taking PrEP—and then they may request PEP. Can you tell me a little bit more about the inclusion about this particular situation in the guideline?
EDH: Yeah. That’s exactly why the guidelines needed updating. There will be times when an exposed individual who has been taking pre-exposure prophylaxis may request a third antiretroviral medication as post-exposure prophylaxis—in other words, three-drug PEP.
We wrote into our guidelines that a clinician may reassure a patient who is taking PrEP with daily adherence—that’s the key, daily adherence—that no current evidence can support an additional ARV after a potential exposure. We also discuss other scenarios, such as PrEP, quote, on-demand, which some individuals are using; or, if there was exposure to virus resistant to the components of PrEP medication, and how to handle those situations.
In those specific situations, you might want to consider giving the exposed patient a three-drug PEP regimen, even though they’re on PrEP.
I just wanted to also add—similarly, we also wanted to address U=U. Right now, there’s no evidence that three-drug PEP provides any additional benefit to an exposed individual if she or he has had consensual sex that meets U=U criteria. We are stating that if a source patient with HIV has an undetectable viral load while on antiretroviral therapy at the time of sex, there is a negligible risk of transmission to the exposed person, and PEP is not indicated.
Now, please note: U=U does not pertain to needle-sticks; it doesn’t pertain to sharing needles. And it also does not pertain to sexual assault, either, where there may be physical trauma, too, because of membranes carrying tissue and exchange of bodily and blood fluids.
TW: What are the correct recommendations for a PEP regimen? What is the first-line regimen that somebody would prescribe?
EDH: Our recommended regimens are either raltegravir or dolutegravir, in combination with two nucleosides—either emtricitabine and tenofovir disoproxil fumarate (also known as TDF); or lamivudine with tenofovir disoproxil fumarate. So, two nukes and one integrase inhibitor. Those are the recommended regimens.
Now, for alternative regimens, we have included a single-tablet regimen that includes a fixed-dose combination—elvitegravir, cobicistat, emtricitabine, tenofovir disoproxil fumarate. This is a one-pill-a-day regimen, also known by the brand name of Stribild.
Other alternatives in addition to this one-pill-a-day regimen include protease inhibitor–based regimens, such as darunavir-boosted ritonavir plus the two nukes I mentioned earlier, emtricitabine, tenofovir disoproxil fumarate; or lamivudine with tenofovir disoproxil fumarate. These alternative regimens, you need to check drug-drug interactions with other medications that the patient may be on. So you have to be a little bit more careful with the alternative regimens, as opposed to the recommended regimens.
TW: The alternative regimens—just to clarify what’s in the document?
EDH: Oh, in terms of the document; the alternatives are Stribild—it’s a brand name—which is a fixed-dose combination of four ingredients: elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate; or one of the protease inhibitor-based regimens, which includes darunavir boosted by ritonavir. There are some other protease inhibitors that are allowed, including atazanavir boosted by ritonavir; or fosamprenavir boosted by ritonavir. And then these protease inhibitors would be given in combination with the two nukes mentioned earlier: either emtricitabine/tenofovir disoproxil fumarate, or lamivudine/tenofovir disoproxil fumarate.
TW: Are there any medications that should absolutely never be prescribed?
EDH: Yeah. We recommend avoiding certain classes of medications, including all nonnucleoside reverse transcriptase inhibitors—so, the entire class of those. We also recommend avoiding CCR5 antagonists and older first-generation protease inhibitors, as well; and older nucleoside medications, such as AZT, stavudine, ddI; and, lastly, abacavir, which is a medication that should be avoided due to risks of hypersensitivity reaction.
It’s rare that these medications are ever even considered. In certain cases of very highly resistant virus, we may look at some of the newer nonnucleoside reverse transcriptase inhibitors. But generally up front, when you’re talking about initial regimens, you should not use those medications in that class as an up-front regimen.
TW: I wanted to ask you about if there are any considerations in the guidelines for people who are of childbearing potential or pregnant. Several years ago during the International AIDS Conference there was a lot of talk about neural tube defects, and I’m just wondering if the guideline addresses any of those concerns.
EDH: We do. The AIDS Institute has published its statement on the use of dolutegravir in any antiretroviral therapy regimen for HIV treatment, or for post-exposure prophylaxis, and acknowledging that there is the possibility of a slight increased risk of neural tube defects in the first trimester of pregnancy, which they define as less than eight weeks post the last menstrual period. This is based on the data from the Tsepamo study that was originally published in 2018 and has had yearly updates since then.
The most recent update on this trial at AIDS 2020 conference has suggested that the difference may no longer be statistically significant. However, at this time the AIDS Institute is still recommending informed decision-making regarding the use of dolutegravir for persons trying to conceive or persons in the first trimester of pregnancy. Raltegravir is another option, and many medical providers have preferred to use this drug, since there is more safety data on its use in pregnancy.
TW: Great. I want to circle back to a new New York State law that allows minors to get into HIV-related prevention services, including PEP, just as they can consent to other reproductive or sexual-health-related services. Why do you think it’s an important state law as it relates to PEP?
EDH: That’s a good question. I think this one is really important because, in order for us to achieve the goal of ending the epidemic in New York State, we need to provide HIV treatment and HIV prevention services to adolescents, as well; and not just adults.
In the past, the issue of parental consent has been a real challenge and sometimes a roadblock. However, with the 2017 amendment, as mentioned earlier, we have more tools now available, and there is less ambiguity about the legal requirements around capacity to consent to pre-exposure prophylaxis and post-exposure prophylaxis.
TW: In closing, I’m just curious about if there’s other important highlights from the guideline that we haven’t talked about.
EDH: Sure. First of all, I think the guideline is very user-friendly. And one example is the PEP patient education checklist, which is included in the guidelines. And it allows the clinician to kind of run through this checklist with the patient, and just make sure that they’re hitting key points.
For example: What is the reason for administering the first dose of PEP immediately? And what is the process for evaluating the likelihood that the patient was exposed to HIV and the risk of infection?
Also on the checklist are things like baseline lab testing that we have to do. What are the potential side effects of the medications? How do you take the medications, including timing and food requirements? What do you do if a dose of PEP is missed?
All of these things are included in the education and counseling checklist, and it makes it very easy for the clinician to kind of run through this and educate the patient.
TW: That’s great. In the guideline, it says that exposure to HIV is a medical emergency. Why was it important to include this statement in the guideline?
EDH: We really wanted to make the point that PEP should start as soon as possible. The clinician should never intentionally wait until the 72-hour mark. The first dose should be given as soon as possible. And then decisions about continuing the full 28 days can be made after.
For example, source patient results may come in after. Or more information on the nature of exposure may come after. We didn’t want clinicians waiting until all that information comes in, in order to make a decision about the first dose. The first dose is STAT; it should be given right away.
TW: Great. Again, congratulations to you and everybody who worked on it. It’s really comprehensive, and I think it’s a great document, and it’s very thorough.
If people want to learn more about this particular guideline, where could they go to check it out?
EDH: I’m so happy that you like it and find it helpful, Terri. I hope other medical providers find it just as helpful and user- friendly. For more information about this guideline, and other information, people can go to hivguidelines.org. It is the website where New York State Department of Health AIDS Institute keeps all of its guidelines. And they can access the post-exposure prophylaxis guidelines there.