Viremic – Cases in HIV

Announcer:
Welcome to Viremic–Cases in HIV, a podcast that explores quandaries in adult HIV clinical care. In each episode, Drs. Eileen Scully and Christopher Hoffmann, HIV specialists at Johns Hopkins, discuss a case, review challenges in the plan of care, and highlight evidence and guidelines that inform clinical decision-making. Now, here is your host, Chris Hoffmann.

Dr. Christopher Hoffmann:
Welcome to Viremic. I’m Chris Hoffmann, and I’m delighted to be joined by a special guest today, Dr. Rona Vail. She’s based in New York City and director of the HIV service at Callen-Lorde in New York City. She’s also the chair of the HIV Clinical Guidelines Committee for the New York State AIDS Institute Guidelines Program, and the lead author of the recently updated PrEP, or pre-exposure prophylaxis guideline.

Rona, I’m so very excited to be talking with you today. Welcome.

Dr. Rona Vail:
Hi Chris, thanks so much for having me on the podcast.

Chris:
On our guidelines committee calls, I always learn so much from your thorough understanding of the real-world application of clinical study findings, including some of the recent PrEP studies. Let me start by asking what drew you to add PrEP to part of your clinical responsibilities as a clinical provider.

Rona:
Well, most of my career, medically, I have been caring for people living with HIV. Still committed to that, still continue to do so. But in 2012, I was very excited when the first PrEP option, TDF/FTC, or Truvada was FDA approved as an HIV prevention tool. I saw it as a potential new era for individuals being able to take control of their sexual health and have sex without fear and also a way of starting to impact the epidemic, the numbers of which were still rising despite all of our efforts at control, and I really wanted to be a part of training providers on this. I wanted to be a part of spreading the word and having PrEP become a mainstream part of what we do in HIV care.

Chris:
I’d like to have more of a PrEP discussion, and as a result, I’m going to present a slightly different case from our typical Viremic case. That is, instead of a person living with HIV, we’ll talk about an adjacent clinical topic—prevention of HIV.

As an HIV clinician, I also manage PrEP and get referrals from primary care providers for PrEP initiation and management. Probably both of us find PrEP to be clinically and socially adjacent to care for people living with HIV. I think this topic will also be of interest to our listeners.

I’m looking forward to hearing your insights and reflections on the literature and how you would manage this composite patient. Let’s get started.

My patient is a young gay black man. When we first met some years ago, he was 28 years old and was referred to me by his primary care provider for PrEP. Just with that information, and as a starting point, what are some of your immediate considerations in a situation like this? And what do you want to know from a patient coming to you on a PrEP referral?

Rona:
Well, first of all, I’m excited that this patient is proactively seeking out PrEP. He is in a category—young gay men of color— who are a high priority for prevention services. It’s one of the only groups where rates of infection are continuing to go up as opposed to dropping. So, I’m very glad that he’s come to clinic today.

I know that I will prescribe PrEP when somebody like that comes in. I will prescribe PrEP for anyone asking for it. And usually, when I can, do a same-day initiation.

But first I’m going to try to learn about him. I want to learn about his lifestyle, his sexual activity. Who is he having sex with? What’s the frequency of sex? What concerns does he have about PrEP? What is his knowledge base about PrEP? What’s important to him in a PrEP option? Is he interested in a daily pill? Is he interested in episodic PrEP? Injectable PrEP? And help to, with him, come up with the best option for him and his lifestyle.

Chris:
Well, I can answer some of those questions. He told me that he engaged in both receptive insertive and oral sex, had a recent new partner, had several partners in the past 6 months.

A little more history in terms of prior sexually transmitted diseases included being treated for syphilis with an appropriate RPR response some years ago. He does use alcohol with sex. He also has used dating apps in the past and suggests perhaps currently, although not in that last month, and is not currently in an abusive or controlling relationship and does not consider himself to be “a survivor of sexual violence.”

Based on that additional information, what are your reflections?

Rona:
Well, the first thing I’m going to want to know is has he had any potential exposure in the last 3 days? Because then we’re going to be looking at PEP before PrEP. He’s still in the window for PEP, so I would want to know—it’s always essential to ask—when the last exposure was.

I think other than that, he seems to be somebody who would be appropriate for pretty much any of our options, and it would depend on him. He hasn’t had a lot of partners—3 partners in the past 6 months. For somebody who is having sex only episodically, the pre- and post-sex or on-demand or episodic PrEP could be an option for him that we’ll talk about.

I’ll talk to him about daily PrEP and whether taking a pill every day is something that he feels he would succeed in or something that feels like it would be a challenge for him and talk about that more.

But there’s nothing in his history that would keep him from doing either daily PrEP, on-demand PrEP, or either of our 2 injectable PrEPs. So, the field is open, and it’s going to be discussion of what he’s leaning toward.

Chris:
First, you asked about when his last potential exposure was, and that was about 4 days ago. He often has sex on the weekend, sometimes related to social activities, and it is in 2 days that he may or may not be having sex as the weekend is coming up.

In terms of that scenario, how would you, first of all, counsel him and advise him, and would that affect at all your consideration of regimen choice?

Rona:
You have a very interesting case and a couple of important issues in there. One is that it’s been 4 days since the last sex. We don’t have any test that will tell us if that person is in early HIV infection because it’s way too soon for either a viral load or an antigen antibody test. In the past, sometimes we would hold PrEP and wait for 2 weeks and have them come back, or a month and have them come back. People were getting HIV in the interim because they had other exposures.

Right now, the recommendation is if somebody’s in the window period where the testing can’t tell us if they have had a recent exposure to HIV or recently contracted HIV, just have them start the PrEP and have them back in a month and re-do the testing then. You don’t want to wait 3 months in that case. You want to have them back within a month to do another test. We would want to still start same-day.

In terms of the weekend, how long does it take for PrEP to become effective? We don’t have an exact time to protection for PrEP. This is all based on pharmacokinetic modeling and not on clinical trials. You can’t really figure this stuff out except through a pharmacokinetic model in terms of levels in the blood and levels in the genital tissues.

For lenacapavir, we know that people will take 2 injections, and pills on the first day, and pills on the second day. If they take their pills on the second day, they are then protected 2 hours after that second oral dose. So, there’s almost immediate protection there. So that could be a good option.

Cabotegravir takes up to 7 days to be protective.

Tenofovir, particularly TDF/FTC, or Truvada, we have very good data that show that if you take 2 pills with your first dose—even if they’re going to take it daily and not 2-1-1—if you start your regimen with 2 pills of TDF/FDC, you will be protected after 2 hours. It’s kind of like the 2-1-1 model. We know that it’s protective after 2 hours. You’re going to get protective doses if you take 2 pills upfront. And that’s true for either penile or vaginal sex, anal sex—all different modes of exposure that 2-hour window before people are protected. So that could also be a good option.

Oftentimes oral PrEP is something you can start same day, whereas injectable preps often need prior authorizations.

I think in that case, and we don’t have data on this specifically for TAF (as far as I’m aware there’s not been studied in this way) it’s possible that taking two pills up front of TAF will decrease the window until you’re protected, but we just don’t have the same data saying, okay, is it 2 hours after or is it 2 days, 3 days? We just don’t have that data.

Chris:
That’s super helpful. It sounds like TDF/FTC or Truvada or lenacapavir, assuring that he gets the 2 days of oral loading, would provide him protection so that he would not need to change his typical sexual activity.

Rona:
I forgot to mention that if you miss the second oral dose on lenacapavir, protection can take 21 to 28 days. So that second dose is essential for immediate protection.

Chris:
Definitely something important to counsel a patient on.

why don’t we go back to some of his blood work? Fortunately, things were pretty normal for him. He had normal kidney function, allowing for any of the PrEP options. On the rapid HIV test, negative. With the caveats you mentioned, that if he had recent exposure, it would not show up on the HIV test. Was hepatitis C negative, hepatitis B surface antigen negative, anti-hepatitis B surface negative, and anti-hepatitis B core negative.

Before getting into what we would recommend in terms of a regimen for him, are there additional services you would recommend?

Rona:
Well, definitely for him, given the testing you just told me about, I would want to make sure he is vaccinated against hepatitis B, since he does not have any immunity, and he’s certainly at risk sexually for that. Other than that, I don’t think so.

Chris:
I’ll give you a little more information on him. So he right now is fairly sexually active, mostly on the weekends, but has a new partner, and as I mentioned, sometimes additional partners. He’s open at this moment to what you recommend in terms of what will keep him best protected from getting HIV. What sort of guidance would you be providing?

Rona:
So, I would ask him whether he has experienced taking medication in the past and what his experience has been with being able to remember to take it every day. You know, the good thing about oral PrEP is it’s incredibly effective if you take it, like 99% effective.

But in the studies for both injectable cabotegravir and injectable lenacapavir, both of the injectable options were superior to the oral options, and not because they’re actually more effective—it’s just because people don’t always take the oral options.

So, I’d want to have a discussion with him about what he thinks his ability to take a medication every day is and whether he feels like that’s going to be a challenge for him or not, and also to see how he feels about needles. For some people, the idea of needles is terrifying, and for other people, the idea of having a needle once every 2 months or once every 6 months and not having to take a pill every day is liberating.

I don’t feel like I would want to sway him toward one or the other. I’d try to come to something together that seems like it would make sense for him.

Chris:
How much of a concern is a late injection or delayed injection in your practice? How often does that happen? And what do you have to do in that situation to make sure that somebody has appropriate protection?

Rona:
Adherence to injection schedules is also somewhat challenging. We have a lot of mechanisms at our health center to send reminders to people, to call people when they don’t come in, to follow up with them, and we do have a window with each of those injections. We have a 1 week before and after window on cabotegravir and a 2-week window before and after on lenacapavir.

We always try to schedule people in the earlier part of the window, like 7 to 8 weeks for cabotegravir, 24 to 26 weeks for lenacapavir, so if an injection is missed, we have a little time to catch up, get them back in and get them an injection.

But if they are going to miss an injection, either planned or unplanned, but particularly if it’s planned, if somebody says, “I’m going to be on vacation next month and I’m not going to be able to get in on time,” during that window or “there’s a family emergency, I have to leave town,” then each of those injectable options can be bridged with oral PrEP options. So, we’d want to make sure they get on an oral PrEP option at the point that they’re due for their next injection.

For lenacapavir, there is an oral bridging option—oral lenacapavir once a week. There is oral cabotegravir, which can be a challenge because it’s only available through a central pharmacy. You’re also able to just give any oral PrEP option. It doesn’t have to be cabotegravir.

Chris:
Got it, back to my patient. Within his social network, there were some other friends who used oral PrEP, and although he did not have experience with routine medication taking as a 28-year-old, he did opt for oral PrEP, and I prescribed TDF/FTC, which is usually my go-to rather than TAF-FTC for a 28-year-old healthy individual.

He did well on this regimen. At the first follow-up visit, he tested negative. He also had tested negative on the HIV RNA testing at 1 month and reported taking the TDF/FTC at least 5 days per week.

Can you walk us through what we may have learned from some of the clinical trials, including perhaps recent findings from Purpose One regarding dose frequency and protection; I guess for Purpose One, at least for women, but with oral options?

Rona:
Sure, let me start first with saying that I’m the same. I like to start with TDF/FTC. It’s cheap, it’s effective. We have more data on it than any other regimen.

But TAF/FTC can be first line for certain people, including we’re now in New York state recommending it for those 19 and under because those folks are still developing bone. In the TDF studies, when people came off of TDF 1 year later, they hadn’t reached back to baseline. Everybody loses a little bit of bone, but usually you gain it back. In the TDF/FTC, 19 and under, they did not get back to baseline, whereas over 20, they did. So that’s one potential place for TAF. The other would be somebody with preexisting bone or renal disease and possibly those at high risk for those problems.

Going back to your other question, we have information on several different things—we knew from the original PrEP studies for TDF/FTC, called IPREX, that those who took 4 or more doses a week were protected. So, it seems 4 four or more doses a week for penile and anal sex is protective.

Now for women and gender diverse folks having receptive vaginal sex, we used to say you needed 5 to 7 doses a week because the tissue levels were not as good. But Jeannie Marazzo this last year published a meta-analysis of 11 studies of cisgender women. And guess what? Four or more doses per week was effective, with only 1 out of 658 individuals with 4 or more doses per week getting HIV. So, the data for TDF/FDC seems to be the same for all kinds of sexual exposures.

Now getting back to your original question about the Purpose One study . . . the Purpose One was a study of cisgender adolescent and young adult cisgender women comparing lenacapavir, our first capsid inhibitor injectable, once every six-month PrEP, comparing it to both TDF/FTC and to TAF/FTC. So, this was a three-arm trial, and this was the first study that was going to look at TAF/FTC for receptive vaginal sex. The original studies did not include this group, so women have been excluded from the use of TAF/FDC as PrEP.

The main result was very disappointing and showed no difference in rates between TAF/FDC or TDF/FDC, and the background incidence of HIV for those not on PrEP. But a further analysis presented at CROI this year by Kiweewa et al., showed that of the 39 cases of HIV in the TAF/FTC arm, 37 were taking little or no oral medication at all, and one of the 2 seroconversions was infected with a strain resistant to the PrEP drugs.

So, you’re getting the same kinds of rates of protection as we expect to see that were the same for the DISCOVER study for cisgender men and transgender women, and same for other studies of efficacy. It also showed that only 2 doses per week led to an 89% reduction in HIV incidence. So, women taking 2 or more doses a week, 89% reduction in HIV incidence with TAF/FTC. Even though this has not yet been FDA approved for this use, this does present to me another option for cisgender women, for anybody having receptive vaginal sex—TAF/FTC.

Chris:
Yeah, to me, it’s a huge move forward in terms of being able to provide greater options for women who want PrEP and also being a little more flexible with some of the dosing and forgiving with a few missed doses.

Back to my patient. He’s continued to follow up with me. We continue to do 3-site testing. I’ve treated him for rectal chlamydia. The most recent visit, he said he actually hadn’t had any sex in the past couple of months, that he was no longer with his partner at the time, and was just going through some life changes. In addition, he said because he had not had sex, he had stopped taking the PrEP.

That makes me nervous because life change can sometimes lead to higher risk activities. How do you approach the situation and how do you counsel patients like this?

Rona:
Well, first of all, you’re right to be concerned. There are very high rates of new HIV infections in people who have been on PrEP in the past and stopped.

First off, I’ll remind him that he can always restart PrEP when he’s ready to start being sexual again. On top of that, I’ll also mention the role of event-driven PrEP—2-1-1 PrEP—and discuss with him having some tenofovir on hand in case he decides he wants to be sexual and doesn’t want to wait for his next appointment with you.

I’ll talk to him about having that bottle on hand and starting it and then getting in to see me if he does start using it again, but I’ll also make sure that I’m mentioning PEP. Anybody who’s stopping their PrEP I will tell them, if you are planning on having sex again, come see me we’ll restart the PrEP no problem, but if something happens, and you have an encounter before you’re able to see me, get in to see me as soon as possible, or see anybody as soon as possible within 72 hours, but preferably within 24 hours, so you can start them on post-exposure prophylaxis.

I think that’s a big deficiency—that a lot of people are still not aware of PEP and are waiting for an appointment, waiting to get a new prescription, run out of medication, and then are off of PrEP for a period of time.

Chris:
In some places like New York State, in the emergency department, PEP is available and mandated by law. Getting people in, as you said, within 24 hours ideally to get started on PEP.

Can you just talk a little bit more about event-driven PrEP—2-1-1 for men? In the updated New York State guidelines, it also has event-driven PrEP for women, which is a new thing. So perhaps just walk us through that also.

Rona:
Originally, I think it was in 2014, we saw the first results of the IPERGAY trial. So IPERGAY (I love that name) was looking at TDF/FTC vs. placebo. It was still ethical at that point to do placebo-controlled trials because we had sort of mixed results for the tenofovir trials for PrEP. So, this was also a placebo-controlled trial. Basically, it was comparing no PrEP to people taking PrEP before and after sex—2 tablets, 2- to 24-hours before sex, (then) 1 tablet 24 hours after the first dosing, and another tablet 48 hours after the first dosing. So, 2-1-1 PrEP. If you’re having sex for several days, it’s 2-1-1-1 until two days after the last sex. That first study was relatively small, but it showed an 86% reduction in new infections.

There was a subsequent larger trial called the Prevenir trial comparing daily to episodic PrEP. In this case, people could choose whether they wanted to go on daily or go on episodic. It was a prospective observational trial, and it showed that both strategies are equally effective. This is not FDA-approved; it’s never gone to the FDA for approval as a dosing, but all the guidelines now include it, given all the data on it.

Many of my patients will go back and forth. In periods of more activity, they’ll go on daily. In periods of less activity, they will go back to the 2-1-1 option. We don’t have any data on 2-1-1 dosing for TAF/FTC.

What’s changed recently, why we changed the guidelines recently, was we don’t have a clinical trial on on-demand or episodic dosing for receptive vaginal sex, but we have pharmacokinetic data. We had a presentation at CROI this year with a pharmacokinetic modeling that showed that 2-1-1 PrEP for receptive vaginal sex would be expected to be about 85% protective. That’s good, but not great. Then they looked at different models of extending that or intensifying that on-demand PrEP. They looked at 2-2-2 (dosing), 2-1-1-1 (dosing), 2-2-1-1 (dosing)—different models of dosing, and what they came up with was 2-1-1-1—so just one additional day of dosing—increased the protection, another 8 to 15%. That now brings you to a very good level of efficacy.

It’s a little bit tricky. I don’t present this as a (and I don’t see this being presented as a) “You could take your TDF daily or pre- and post-sex.” I will say for somebody who is struggling to take a pill daily and doesn’t have sex frequently enough that they feel like they want to take a pill daily and doesn’t want to do injections, and I know they’re having risk, then I will talk about 2-1-1-1. I want a little bit more clinical data to just say, “Hey, you could do it this way or this way.” But I do feel like it’s a reasonable harm reduction approach. The New York State guidelines agreed with that approach and feels like this is a reasonable option for that kind of person.

Chris:
Yeah, I think the data are fairly compelling. More clinical data would certainly be helpful. My PrEP practice is nearly all men or entirely men. So, for me, it’s event driven PrEP, just the 2-1-1. In terms of this patient, that’s what I did discuss with him, and I told him that I wanted him to have TDF/FTC on hand and that he should feel comfortable in using the 2-1-1 approach and even keeping a pill in the pocket potentially if his situation may change or had any possibility of changing.

In addition, as you highlighted, I always bring up the issue of PEP, which I would agree does not get enough attention or perhaps awareness in the general community. Like a number of my PrEP patients, although he has been off of PrEP for a while, he does continue to follow up with me, mostly for primary care issues, and has used the 2-1-1 option a few times and continues to be testing HIV negative. I have had to manage a few STDs along the way but otherwise is doing well.

Any other comments you’d like to make Rona in terms of prescribing PrEP, increasing PrEP use, or specific considerations around PrEP.

Rona:
Absolutely. The first thing that I want to highlight is how much having choices matters. There was a study last year called the Dynamic Choice Study. It showed that given a choice between oral and injectable PrEP, and allowing switches where desired, and that people had options, it increased persistence on PrEP by 69% and decreased new HIV infections. That was before lenacapavir was available. So that was just 3 PrEP choices. Now we have 4 PrEP choices. So, choices really matter.

I think we have to look at the barriers to PrEP, you know, and that there are both structural and individual barriers to PrEP, particularly within certain communities. We know that, when we look at the most recent data, white individuals were uptaking [sic] PrEP—63% of PrEP users were white in 2024, but only 24% of new diagnoses are in people who are white.

In black and African Americans, 15% of PrEP users, but 38% of new diagnoses. So real discordance there, and the same for Latino, Hispanic, Latinx folks—32% of new diagnoses are in Latino and Hispanic folks, but only 18% PrEP use.

Women are under-utilizing, young people are under-utilizing, and transgender and gender diverse individuals are also under utilizing. These are folks that we want to engage. So, we do have to look at the barriers, both like I said, individual and structural, awareness, stigma, distrust of medical systems, cost.

But we also have the structural issues of affordable insurance, access to PrEP providers, we need more community providers, discrimination that people fear or face, and medical providers who shy away from discussing sex and sexual health and PrEP.

So, we have a lot of barriers to overcome, and we can do that. We can overcome them with some real community-based education, peer support, finding trusted community members, tailoring our advertising, training more PrEP providers, looking at healthcare models like telehealth. We really need to be doing better on this in the communities most impacted by HIV.

Chris:
Yeah, Rona, couldn’t agree more. I think there’s a need for greater PrEP awareness in the community, as well as less reluctance, as you said, to discuss sex and to discuss HIV prevention, as well as STI prevention, and just healthy and positive sexual experiences.

And certainly, both within the specialist community and the primary care community, it would be great to see more PrEP prescribing and PrEP management.

Also, Rona, when we’re talking about different providers, just wanted to refer back to my patient who wanted to be on oral PrEP (he) started on oral PrEP and was doing well, and there are fewer barriers logistically for prescribing and monitoring oral PrEP, and also sometimes greater ease in terms of shifting from intermittent use to daily use.

I think it’s also a lower barrier for providers. So certainly, I encourage people who are providing care, who may be intimidated by the logistics of injectable PrEP to at least consider starting oral PrEP in somebody and certainly getting somebody started right away and then referring them is much better than having them wait a month or 2 to seeing a specialist when they may seroconvert.

How do you approach that?

Rona:
Absolutely. I think that injectable PrEP, first of all, technically—the technicalities of it, and how to do it, and what tests you have to order, and how you monitor it—it’s actually relatively simple, straightforward medicine. The challenge is in the implementation. That’s where a lot of health centers get stuck, understandably. It takes a lot of coordination of care, a lot of staff to be on top of the numbers, of all the different pieces—the prior authorization that these drugs need, but also the tracking, the distribution, keeping track of patients or individuals, making sure they’re on time for their injections, calling people back, making sure insurance is actually up to date and valid, figuring out how you’re going to bill, whether you’re going to do buy-and-bill or pharmacy purchase. There’s so many things to be considered and that’s, I think, overwhelming for smaller practices. It is doable for larger practices, but it does take a lot of coordination.

So, I think at least providers should be very comfortable and very willing to give oral PrEP, either TAF/FTC or TDF/ FTC, and find referral sources for injectable PrEP if they’re not able to manage all the logistics. It is a big financial commitment, personnel commitment, a lot of coordination of care with the injectable. So that can be roadblock and a barrier for some people.

Chris:
Thanks so much, Rona. This has been a real pleasure discussing PrEP with you. And I hope our listeners have enjoyed it as much as I have.

Rona:
Thanks Chris, this was fun. I enjoyed it very much.

Announcer:
Thanks for listening to Viremic. If you enjoyed the show, please subscribe wherever you listen to podcasts. We’ll be back in a couple of weeks with a new case to discuss.

Viremic is sponsored by the Clinical Guidelines Program, a collaborative effort of the New York State Department of Health AIDS Institute and the Johns Hopkins University Division of Infectious Diseases.

Visit the program’s website at HIVguidelines.org.

The podcast is produced and edited by Mary Beth Hansen and Brian Hatcher with appreciated assistance from Jesse Cicotte and Laura Lebrun Hatcher.

Viremic’s case discussions are presented for informational purposes only and are not offered as medical or clinical practice advice for patients or clinicians. Any mention of specific medications or commercially available products is a description of use, not an endorsement.