The 10th International Workshop on HIV and Women was held this past March in Boston. Although COVID-19 prevented some participants and presenters from attending, 116 people gathered together to share knowledge and life experiences. It was the only event affiliated with the Conference on Retroviruses and Opportunistic Infections (CROI) that went ahead.
During the workshop, Giffin Daughtridge, M.D., and Linden Lalley-Chareczko, M.A., gave a poster presentation titled, “Disparities in PrEP Uptake and Adherence: Implementation of Routine Adherence Monitoring in a Philadelphia PrEP Clinic.”
Giffin Daughtridge has an M.D. from the University of Pennsylvania and an M.P.A. from Harvard Kennedy School. He currently serves as the cofounder and CEO of UrSure, Inc., a diagnostics startup that makes tests to measure and improve adherence to pre-exposure prophylaxis (PrEP) and antiretroviral therapy. Giffin has been a Fulbright scholar, a Zuckerman Fellow in the Harvard Center for Public Leadership, and was named to the Forbes “30 Under 30” list for health care.
Linden Lalley-Chareczko holds a master’s degree in forensic psychology and has 11 years of professional research experience. She’s published numerous papers in several fields, including in forensic psychology, behavioral sleep medicine, and HIV treatment and PrEP. Currently, she is the research program director for Philadelphia FIGHT Community Health Centers.
Terri Wilder: Before we talk about the information you presented at the 10th edition of the International Workshop of HIV and Women, I’d love to hear more about each of your interests in PrEP research and the organizations you work for. So, I’m wondering, Linden, if you would mind sharing that information first.
Linden Lalley-Chareczko: Sure. Well, I started at Philadelphia FIGHT in 2013, just as PrEP was starting to be prescribed to patients. It was FDA approved—well, Truvada was FDA approved in 2012 for the purpose of PrEP, but it usually takes a few months for things to get off the ground. So, right as I was starting at Philadelphia FIGHT, PrEP was starting to be discussed amongst the medical leadership there. And we did years of research as a vehicle to gain some funding to start the first PrEP-focused clinic at Philadelphia FIGHT.
TW: Great. And what about you, Dr. Daughtridge?
Giffin Daughtridge: So, actually, the same clinic, the clinic at Philadelphia FIGHT, I started working there back in 2013. And then through that work, with my cofounder, Dr. Helen Koenig, we developed—well, with Children’s Hospital of Philadelphia—the initial app-based urine test. And then that ultimately went on to start UrSure, which is now a company, a startup company based in Boston, that makes diagnostic tests to measure the levels of PrEP and HIV treatment in patients’ systems so that we can identify which individuals are struggling with adherence and need more support.
TW: So, you decided to work together because you guys had a connection to Philadelphia FIGHT, right?
GD: Yes.
LLC: Yes. I was, at the time, at Philadelphia FIGHT. I was a research assistant. And Dr. Helen Koenig had received some funding from the Center for AIDS Research at the University of Pennsylvania. So, it was through that opportunity that I was able to work as the research coordinator on the first, sort of, founding study that helped establish the first clinic, as well as the first time we tested the idea of measuring tenofovir in urine for the purpose of adherence monitoring.
TW: Great. Can you give me some background information on the issue of PrEP uptake and adherence and, really, what was the purpose of the study?
GD: OK. I guess, just quick background on PrEP uptake and adherence. What we’ve seen is, for PrEP to be effective you need three legs of a stool—you need PrEP uptake, you need adherence, and you need retention in care.
Unfortunately, for some of the more vulnerable populations, there has been a struggle around all three of those legs of the stool. And so, with the study, what we were looking to do is focus on the population, obviously, of women, where you see about 20% of the HIV infections in the country, but only about 7% of PrEP users. So, there’s been very low uptake.
And then, in a number of different studies, PrEP adherence has also been a real struggle in women. And so we were hoping to get a better understanding of women on PrEP at Philadelphia FIGHT, and using the objective levels of adherence with the test for that.
TW: Great. When was the study conducted?
LLC: Well, it was a retrospective chart review. So, we analyzed all of the records we had. We have been implementing the urine tenofovir test in our clinic for folks who are on PrEP for some time. So we took a look back through any of the patient medical data that exists in our EMR [electronic medical records] for folks who were taking PrEP during the study time frame and that also had at least one corresponding urine tenofovir test.
TW: Can you tell me more about the development of this urine-based adherence test, in terms of how and why it was developed?
GD: Yeah. The initial genesis of this was, when the PrEP clinic was started at Philadelphia FIGHT back in late 2012, early 2013, with a number of patients who were coming in and picking up PrEP, as you see in a lot of chronic medications, self-reported adherence tends to be a lot higher than actual levels of adherence. And this played out in our clinic, as well.
What happened as a result is, people would come in to pick up their PrEP refills. You would have a conversation with them about their adherence levels. And everybody would self-report: “Oh, yeah. I’m taking my PrEP. I’m not missing any doses.” But we actually had a couple seroconversions, where individuals became HIV positive, even though they were on PrEP and self-reporting high levels of adherence.
As a result, we realized that what we really needed was an objective way to identify who was, and wasn’t, taking the medication, so we could then allocate resources to those individuals who needed more support. So, that was kind of the original genesis of it.
TW: Tell me a little bit more about the methods, in terms of, you went through the medical charts—and then what happened after that?
LLC: Yeah. So, what we did was we reviewed the medical charts of anyone who was prescribed PrEP during the study time frame, which I believe was, if I’m not mistaken, Giffin, October 2018 through August 2019.
GD: Yes.
LLC: Basically, at the point that the urine tenofovir test became commercially available as an order code—and we’re able to fully implement this in a non-research way across all of our clinics that were prescribing PrEP.
Using our electronic medical record, we looked back during that time frame of anybody who was prescribed PrEP by one of our clinicians and also looked to see if we had a result from a urine tenofovir test. And then we then also extracted gender, sex assigned at birth, age, sexual orientation, other relevant variables. Everything was collected in a de-identified way and stored in a database that’s completely separate from our EMR.
TW: So, in your methods section, it talked about the fact that providers receive results indicating if the patient was recently nonadherent. And then the patients whose results suggested suboptimal adherence received enhanced adherence counseling.
LLC: Well, that’s our standard-of-care practice. That wasn’t for the purpose of the study. That’s just our standard of care at Philadelphia FIGHT.
TW: Right. So people use this phrase, enhanced adherence counseling; but I can’t ever get a specific definition, or what exactly does that look like. Can you tell me specifically what the enhanced adherence counseling involves?
LLC: Well, at FIGHT, it is really tailored to the individual patient. So that’s probably why you can’t get a really good definition of what it looks like; it’s because everybody’s circumstance is so very different. Philadelphia FIGHT has dedicated PrEP retention coordinators, whose job it is to meet with patients who are taking PrEP one-on-one to discuss things like adherence, any types of barriers, housing issues, food insecurity, mental health issues—help refer people to mental health care if they need it, employ motivational interviewing techniques for when people are struggling.
You know, that answer of, “Oh, well, I just can’t remember.” Well, that can mean a lot of things. So, a PrEP retention coordinator can sit down with someone and say, “What has life looked like for you for the last week?”
Or maybe even if things—if this has been a pattern—“What is life like for you over the last couple of months?” And help a patient decide what would help them remember to take their PrEP.
Maybe pairing it with an event, like a meal, or pairing it with brushing your teeth every night. Or trying to pair it with a location. You know? Like, “Home is not a safe place, but if I remember to take my PrEP when I get to class every morning, that’s better.” That’s better if, for some reason, home isn’t a safe place for them.
So, enhanced adherence support can look like a lot of things.
GD: Terri, just to add on to that: We, UrSure, works with about 25 different clinics across the country. We’ve run over 7,000 samples in those clinics. And when we’re setting up a new clinic, we often talk to them about best practices. You’ve run the test, you get the data back, send in the ideas. OK, great. That’s just a piece of data, unless you can actually action them, like Linden’s saying, and turn that into a behavioral change.
So, what we recommend is kind of a three-step process that’s kind of loosely based on Dr. Rivet Amico’s Integrated Next Steps Counseling, where you share the results with the patients; you discuss their barriers to adherence; and you bring strong ways to improve it. So, those three steps have been shown in a study she did with Dr. Landovitz at UCLA to improve adherence by about 50%, if you use an objective adherence that’s paired with that three-step counseling method. That’s what we use to recommend to clinics—kind of a simple framework to think about adherence counseling.
TW: Great. In the presentation that you gave at the workshop, tell me about the results from the study.
GD: Yeah. So, I think there were two key takeaways. One was, the N was very small. So, when you look at the number of people receiving PrEP at FIGHT—and this is a trend we see in clinics across the country, every clinic we work with—the number of women on PrEP, especially cisgender women, is extremely low. We saw that at the site; I think the N was only eight or nine.
What we also see is that, in addition to the low uptake, adherence tends to be two to three times worse in women than what we’ve seen in MSM [men who have sex with men], that we use as the comparative population. That played out here, as well. The nonadherence rate, I think, was 50%. Again, a small number. But it looked like it was actually statistically significant when we ran some additional data after, I believe, the presentation of the poster. I talked to our team today, and they said that it did end up being statistically significant, the difference in adherence between women and men, at Philadelphia FIGHT.
TW: And so, your results were—just to clarify—you had 185 adherence tests that were conducted over the study period; and 159, which was 86%, of which showed recent adherence. And then the majority of tests were conducted for sex assigned at birth males and cisgender male, which was 94%, 85%, respectively.
LLC: Correct.
TW: Were there any surprises in your results?
LLC: I don’t know if the results were surprising. I think they substantiated the point that’s being made more and more, that women are still underrepresented in the PrEP conversation, as a whole. And Philadelphia FIGHT is an organization that takes PrEP within general sexual health and general sexual wellness practices, you know. We are trying our best to use PrEP as a tool for anyone in the community of Philadelphia, which is a high HIV-incidence community, who is having unprotected sex or having sex with persons that they can’t discuss serostatus with.
So, even though our approach to PrEP may be different—we’re not targeting communities; we’re targeting sexual wellness for everybody—we’re still seeing a low number of cisgender women taking PrEP.
TW: As I was looking at your poster, the first thing that kind of came to mind for me was, is there any opportunity to do in-depth qualitative interviews with any of the participants to really find out the specific issues related to nonadherence, as well as adherence? And I realize that the focus of this, because it was in the context of an HIV and women workshop, was on women.
But I was also really interested to learn more about why the participants who were assigned male at birth and non-binary, as well as assigned female at birth but identify as male, had such good adherence. I mean, I realized it was a very small N, but would still be really interested in what they would say.
LLC: I think that is a really interesting question. Qualitative research like that is something that we love at Philadelphia FIGHT. We love to hear firsthand what’s working, what’s not; how folks have navigated the health care continuum; how they’ve had success; how they’ve handled times where life was stressful and maybe they weren’t as successful at adhering to any treatment, whether it’s PrEP, hormones, or medication for any other chronic condition that they have. So, it’s a possibility, and something we—I don’t know—guessing something we’ll probably pursue in the future.
GD: Yeah. And, Terri, there was just a great publication put out. Matthew Spinelli and Monica Gandhi did a paper, where they did such very in-depth qualitative interviews with individuals who had been on PrEP, or were currently on PrEP, when they seroconverted. And at least three of those were trans individuals. So, I could certainly send you that paper. It just came out a couple of weeks ago. And there’s really good stuff in there.
TW: Great. After doing this study, has the PrEP clinic started doing anything differently as a result of these findings?
LLC: I would say our biggest changes in how we’re approaching PrEP actually came sort of at the same time that we were working on this poster and submitting it to CROI. PrEP uptake in women has been something that’s sort of been kicking around in the back of our minds and, you know, how do we get more women at least knowledgeable about PrEP? We worked with other agencies to do research on the PrEP education in women front.
But we made the conscious decision, like I said, to take a sexual wellness approach to PrEP. It is a tool in a forever-growing toolbox of sexual wellness for anybody who is sexually active with anybody else. So, we’ve worked with some med students from Jefferson Medical College to come up with looping video advertisements and print advertisement material that situates PrEP within, like, general sexual wellness, hoping to appeal to more sex ed of our female patients. Just, you know, when you lay out PrEP as one tool, just equal to birth control, a condom, a morning-after pill, HPV vaccinations—all these things that a sexually active person should be thinking about—we’re hoping that that will help bolster our uptake in folks who were assigned female sex at birth, whether or not they’re cisgender female or a transgender person.
TW: Great. So, any other research plan for the future around this topic?
GD: Yes, UrSure has a number of collaborations, where we are increasingly doing work with adherence levels in cis women. We’ve got five different collaborations going on, both domestically and internationally, specifically looking at PrEP adherence in women.
So, yeah. More to come soon.
LLC: More to come from FIGHT, as well. We hope to work more with Jefferson University and the University of Pennsylvania, specifically looking at this topic—whether or not it’s qualitative or larger quantitative research partnering with the PrEP program at U. Penn. Definitely more to come from FIGHT, as well.