Viremic – Cases in HIV

Announcer:
Welcome to Viremic–Cases in HIV, hosted by Dr. Eileen Scully and Dr. Christopher Hoffmann, both HIV specialists at Johns Hopkins, who explore quandaries in adult HIV care. Each case discussion includes
medical history and diagnoses, challenges in care and treatment, and key evidence and guidelines
that inform clinical decision making.

Cases are presented as a composite from the hosts’ clinical practice, with all identifying details removed to protect the privacy of patients. Case discussions are for informational purposes only and 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 only, not an endorsement.

Dr. Christopher Hoffmann:
Welcome to Viremic. I’m Chris Hoffmann, and I’m joined today by a special guest, Dr. Asa Radix.
Before we start, I’d like to say if you like this podcast, please share with a colleague and follow us wherever you access podcasts. In addition, we’d love hearing from listeners. Please send questions or future topic suggestions to us at viremicpodcast@jh.edu.

Asa Radix is an HIV clinician and a leader in advocacy, research, and policy for transgender people. He practices at the Callen-Lorde Clinic in New York City, where he’s the executive vice president of research and education and a longtime member of the Adult HIV Guidelines Committee of the New York State AIDS Institute Clinical Guidelines Program and on the DHHS ART Guidelines Panel. Asa has kindly agreed to join today’s episode to discuss a case involving a transgender woman. Welcome Asa.

Dr. Asa Radix:
Thank you, Chris. I’m happy to be here, and I want to say thank you for taking on this topic. It’s important, and honestly, it’s very timely.

Chris:
Asa, it’s so good to have you. I wanted to start by asking how or why you got involved in caring for people living with HIV.

Asa:
Thanks for starting there. I came into HIV care at a very specific moment in time. I started my internal medicine residency in Hartford; it was 1990 at the height of the HIV epidemic. As you know, it’s hard to describe what that felt like unless you trained in that era. A lot of the patients who were coming in were young people, and they were facing what was at the time a really devastating illness with very limited treatment options. As you probably know, it wasn’t just clinically intense, it was emotionally intense, and it left a mark on all of us who trained during that time. AZT was only just being introduced, and it was a step forward, but it wasn’t the breakthrough that people needed. Then I started an ID fellowship, infectious disease, and that’s when we started seeing the first combination regimens. It was one of the most remarkable transformations I’ve seen in clinical medicine—suddenly having real hope that people could survive this and live well.

Around the same time, I started seeing a broader range of people, not just young cisgender gay men affected by HIV, but cisgender women, and also trans and gender diverse folk. Mainly at that time it was transgender women. One of the things that stood out to me immediately is that there was no research being done. These groups weren’t being talked about. There wasn’t a clear understanding of the care that was needed or the barriers that trans people faced in accessing care and barriers that affected every part of what we now call the HIV care continuum—access to testing, linkage, engagement, treatment, staying on treatment, and being virally suppressed.

That’s where it all started. So over time, HIV care, for me, became much more than about prescribing antiretrovirals and other medicines to prevent and treat OIs. It became much more about equity and building systems that people could trust and stay engaged in care. I’ve been focused on trans health and transgender people and HIV ever since that time.

Chris:
These are certainly challenging times for transgender people with the federal government seeking to eliminate the existence of transgender people. Why is this particularly relevant when we consider HIV care?

Asa:
It’s extremely relevant, and I’m glad that you’re naming it upfront as an important issue—HIV care and treatment. It’s one of those areas where the science is very strong. We have excellent treatment, excellent medications (also now for HIV prevention). People are living with HIV and can expect a normal life expectancy, but outcomes still depend on whether people can access care safely and consistently.

Shortly after the new administration came in last year, there were several executive orders, as you know, that had the effect of removing all references to trans people, including stating, essentially, that they don’t exist. When the broader environment—the political environment, cultural environment, also legal—is actively trying to erase trans people, it sends a very clear message that they may not be safe, and that message, I believe, follows people into clinics, into hospitals, pharmacies, just about everywhere. So even if you have a great clinician sitting across from you, this system matters. It affects whether someone’s going to get tested, whether they’ll trust the result, whether they’ll even come back to the clinic, whether they’re going to fill their prescriptions, whether they’ll stay engaged long enough to achieve viral suppression. So, this isn’t just about politics; it directly impacts HIV outcomes. I think it’s a travesty what has happened over the last year.

Chris:
To follow up on that, you’ve mentioned to me that some state medical schools have disallowed the discussion of transgender people in the curriculum. How does this affect access for transgender people?

Asa:
It’s definitely already happened. I was interviewed about this in the last few months. There are at least 3 medical schools (maybe more) in Texas that have stopped training medical students on transgender health. This doesn’t eliminate trans people; it just means that eventually they’re going to receive substandard care. If clinicians aren’t trained, if trans health is being literally erased from curricula, then patients are walking into settings with staff don’t even know the basics—the basics being how to create an affirming setting, respectful language, anatomy-based screenings, how hormones work, drug interactions, how to ask questions without stigma. Clinicians may not know how to safely monitor individuals who’ve had gender-affirming interventions like hormones or surgical interventions. I’ll give you a few examples—the need for breast cancer screening for trans women on estrogen. They may not be aware of that or the best practices for cervical screening for transgender men.

This impact on clients goes really far. The policies communicate that trans lives don’t matter. It prevents trans people from getting clear and accurate information from their clinicians in order to stay healthy, and it undermines trust in health systems. I expect it’s going to have very direct consequences. It’s going to lead to delays in care, people avoiding care, people lost to care, which obviously is important in HIV medicine. People will stop disclosing information that they need to share with their providers because they don’t feel safe. For HIV, where it’s so important that we have trust and continuity, this is a serious issue. Providers want this information to be able to provide appropriate care; so, it’s a disservice not only to the clients, but also to clinicians.

Chris:
Well, hopefully we can discuss some best practice for HIV care overall and HIV care focused on transgender people. So, I’m going to go right to our case now. A patient I saw was a transgender woman with a recent diagnosis of HIV. She’s a 32-year-old woman. She’s currently unemployed, sharing an apartment with a roommate and has a pet cat. She was diagnosed during HIV testing while receiving gender-affirming care. Her diagnosis viral load was 82,000 and her CD4 count 365. She also had HIV drug resistance testing for RT and PR, and no resistance mutations were identified. She has no other known major medical conditions.

What else would you like to know before discussing a care approach with her, especially in regard to recommending an antiretroviral therapy regimen?

Asa:
This is a great case. I love the way you framed it as supporting her health. First, I want to know the medical basics. Any prior antiretroviral therapy use? Has she used PrEP? Any important past medical history that we should know? What about her kidney function? Probably hepatitis serologies. We usually get STI screening, so, I want to know the results of that. What other medicines does she take? Tobacco and substance use? That sort of thing that we do for all of our clients.

It’s also important to know specifically what’s going on in her life right now. Does she have stable housing? Are there insurance issues? Is she worried about privacy? Is she worried about perhaps someone seeing pill bottles? Is there a history of depression or trauma? Anything that’s going to make a daily routine harder because, mostly, people are expected to go on a daily regimen.

What kind of support system does she have? And especially for trans clients, there’s some particular questions you’re going to need to ask, especially about their hormone regimen if they’re on it. Are you taking any hormones and what hormones are you taking? Are you taking blockers? Have you had any gender-affirming surgeries, because that’s pertinent, especially if they’ve had bottom surgery or genital surgery. Are you planning on starting hormones? Are you planning on a surgery? And specifically, have you had any negative experiences with healthcare around your gender care? That context shapes everything for clients. Are they feeling safe? How much do they trust you? And whether they feel like they can come back.

Chris:
Great questions. I will try to provide answers to some of those; some I unfortunately did not go into with her. She considers her current housing situation with a roommate as a stable situation. In the past, she has been unhoused, never in shelters or on the street, but couch surfing with friends. She does have sex with cisgender women and men. Smokes about half a pack of cigarettes a day, drinks alcohol socially, and does not inject drugs. In terms of gender-affirming care, she is taking spironolactone and oral estrogen, has not had any gender-affirming surgeries, and additional laboratory testing is notable for normal kidney function and negative for hep B surface antigen, hepatitis C antibody, and syphilis antibodies.

Given this information, are there any differences in HIV-specific care for her that you would consider compared to a non-transgender patient? What should I be aware of in thinking about her HIV-specific care or antiretroviral therapy regimen? We can get into some of the primary care things that you brought up later.

Asa:
The basics are the same. Ultimately, our goal is to initiate ART and to have her virally suppressed and healthy with a good quality of life.

This is an interesting case, but it’s also a very straightforward case, at least from a medical standpoint—no-drug-resistance mutation, normal kidney function, moderate viral load, CD4 count is fairly good. What’s different is the experience of accessing care for her. Often navigating difficult systems, stigma, and we’ve talked about safety concerns. As the person comes in, you want to create a setting where she’s comfortable. You can help this by asking her what name she uses, especially if it’s not the name on her current legal ID card. You should be asking about the pronouns she uses and honoring that. You can also provide her with community resources. Maybe we can talk a little bit about that at the end.

You said she was diagnosed during a gender-affirming care visit. That’s good; it creates an opportunity because she’s already connected to care in a meaningful way. And also, she’s taking hormones regularly. This supports her ability to adhere to an ART regimen. I should have said that before. That’s also something that you can ask.

You did say she was a smoker. That is concerning. It matters, especially over the long term, not because we want to overwhelm her on day one, but because HIV and smoking is a big cardiovascular risk driver. She’s also on estrogen; that can increase risk for venous thromboembolism with active tobacco use. So, I would say tobacco cessation is something we would want to weave into primary care, maybe over time.

You said she had hep B surface antigen-negative, but we need to clarify the hep B immunity. A surface antigen negative is good, but I need to know if she’s immune or susceptible, whether she needs to be vaccinated.

You also want to address sexual health issues. She may need STI screening. So, for this, you do need to know, if you have a trans client, this client hasn’t had any surgeries, but generally if you do have someone ask about anatomy. For example, if you have a person who’s had a vaginoplasty or creation of a vagina, you need to know that so that you know what sites to do STI screening. Overall, it’s not radically different HIV care, but definitely more attention to how we’re going to keep her engaged and feeling safe and supported.

Chris:
One of the issues that’s sometimes on the minds of medical providers, and often on the minds of people on gender-affirming medications, is how an antiretroviral therapy regimen will interact with or affect their gender- affirming journey. How do you approach the situation and counsel patients? And do you have a go-to ART regimen when there’s not complex drug resistance mutations?

Asa:
This is an important point. There’s been quite a bit of research on this—how to address this issue with clients. There was a study where about 40% of trans women participants reported taking ART, hormones, or both differently than prescribed because they were concerned about interactions, showing that trans women may be afraid of drug-drug interactions, and as a result, they may not take ARTs prescribed. It is important to address the issue and not wait for them to ask.

When a client is in front of me, I usually start by validating these possible concerns. Some of the language I might use would be, “Of course, you might be worried that HIV medicines or ART can interfere with your hormone therapy. I know that hormones are essential care for you, and I want you to know that I’m protecting this treatment, and this is a priority for me as well.” I can then assure them, in almost all cases, we can treat HIV effectively without interrupting a hormone. So that’s just an example of how to say it.

Also, reassure clients that you’re going to continue to monitor their hormones, especially the serum levels of testosterone and estrogen to make sure that they’re getting the correct doses. The goal is to choose a regimen with few interaction concerns. If you are concerned, you can always adjust hormone doses. It’s pretty easy to do. And let the client know that you’re going to do it together with them. But it’s important that they’re not changing doses or spacing doses out of the ART without discussing this with you because of the fears of a drug-drug interaction. Again, it’s so important to always reassure clients about this.

There were guidelines that used to exist as part of the HHS ART Guidelines for Adults where they showed different ART regimens that had the least potential to interact with some of the medications we used for transition, like estradiol and testosterone. These include INSTIs, some of the NNRTIs like doravirine and rilpivirine. We know that some boosted agents like with ritonavir or cobicistat can impact estradiol levels. For example, ritonavir-boosted proteases. Also, efavirenz and etravirine can lower estradiol levels. But again, if you’re monitoring the levels, you can always make adjustments to someone’s estradiol dose. It’s very easily managed by monitoring and adjusting.

Chris:
Given what you said, that we can often adapt and adjust hormonal therapy to drug-drug interactions with antiretroviral therapy, do you have a favored or a go-to ART regimen for your patients on hormonal therapies?

Asa:
Probably not. Most of the time, I use the same principles for everyone. A regimen that’s effective, easy to take, well tolerated, durable, and so on. Many people do best on a single-tablet regimen because they’re effective and simple. But the truth is, the best regimen is the one that someone can take consistently and they feel comfortable with.

In someone like this, with normal kidney function, you said no resistance, they have no chronic hep B, we have a lot of options, but I still lean toward the once-daily single-tablet regimen. We use a lot of bictegravir/TAF/FTC, but there are other options that you can use.

Chris:
Maybe we can touch on lenacapavir as well. Certainly not part of a regimen for this patient, but a very important regimen for PrEP as well as for treatment in more complex drug resistance or adherence challenge scenarios. I know that lenacapavir is a moderate cytochrome P453A4 inhibitor, which could raise some concerns for interactions with hormonal therapy. I don’t know if you want to touch on some of the sub-study findings from the purpose II trial in lenacapavir and hormone therapy.

Asa:
This is a good question, but it holds throughout that we do not need to be worried about drug-drug interactions with lenacapavir or any ART with the medications that we use for transition, whether it’s testosterone or estradiol or even the common blocking agents that we use. The key aim is to continue ART, and to monitor sex hormone levels, and to make the minor adjustments that are needed. In 99% of cases, you’re not going to need to make any adjustments whatsoever.

Chris:
That’s very helpful. The take-home for me is in any situation to provide hormone therapy monitoring as needed and be especially mindful of that in somebody on a cytochrome P450 blocker like cobicistat or ritonavir.

In addition, the sub-study on lenacapavir showed no significant drug-drug interactions. That said, always a healthy practice to monitor hormone levels.

We now have my patient on antiretroviral therapy with a regimen that she feels comfortable with and feels is not going to make a big impact on her gender-affirming therapy. However, you’ve already mentioned that access to care and care acceptability can be a challenge for transgender people. How can we as doctors and nurses and other health care providers do our best to support ART success for transgender people?

Asa:
I’d start by saying that many of the same principles that support success for all patients apply here as well—things like addressing stigma, unstable housing, gaps in insurance, and even fear of losing insurance, and of course, supporting mental health needs. But for trans and gender diverse people specifically, we also have to recognize that access to gender-affirming care is often their top priority, and when that care is delayed, denied, or separated from HIV services, it becomes a barrier to engagement. When it’s integrated and supported, we see that it can improve outcomes.

We have some compelling data on this. The Legacy study was a cohort of trans and gender diverse patients from 2 federally qualified health centers, and Callen-Lorde was one of them. We found that for trans people living with HIV, if they got gender-affirming hormone care, they were more likely to achieve viral suppression. We have other studies as well, including a study from Montefiore Medical Center in the Bronx that showed that access to hormone therapy was associated with better retention in care and higher rates of viral suppression among trans women. The key takeaway here is that gender-affirming care is important to optimizing HIV outcomes, and hopefully this is an important principle that listeners can take away.

Chris:
That’s a powerful message. For patients who are on gender-affirming hormone therapy but have not had surgical affirming therapy or other approaches, do you discuss this with your patients, bring up additional options for gender affirmation, or how do you even broach this topic with your patients?

Asa:
It’s actually quite easy, and sometimes clients are coming in with specific goals and needs. Generally, if they’re coming in, they have a question, and the question might be, “How can I start this treatment,” if they haven’t already. They might have questions about the efficacy of the treatment, or what’s the best formulation to use, and what are the best doses, and how long should they be on it, and how long will it be before they experience changes? These are all things that we discuss when people come in.

We don’t expect everyone to be experts in the field, but hopefully you can use different resources to be able to assist clients. You can also obviously ask experts in this care for tips on how to provide it. I do believe that most clinicians can provide this care easily and safely.

Chris:
Now that we have her on antiretroviral therapy, how do you approach primary care for a patient like this? What are some of the nuances for a trans woman or a trans man? Things that jump into my mind immediately are some of the issues around cardiovascular health, bone health, and cancer screening, including cervical cancer, prostate cancer, and colon cancer. That’s a lot.

Asa:
We won’t be able to touch on everything today. At Callen-Lorde, where I work, we have a phrase. We used to use it on a lot of client-facing educational materials. It said, “If you have it, check it.” And it’s so true. If you have it, check it.

We can, for example, start with cancer screening. We should be providing anatomy- and risk-based screening, delivered in an affirming way. So don’t just focus on screenings that traditionally men should have or women should have. We need to think about someone’s anatomy. If you have a transgender man in front of you, and he’s had top surgery, which is a mastectomy, they removed breast tissue, they don’t remove all of the breast tissue. So, you need to know that, as a clinician—okay, there’s still breast tissue. So, this young man might in the future need to get breast cancer screening. That’s something you should be discussing with the clients. We use shared decision-making for that.

It’s also important to know that for transgender women who’ve had estrogen and now have breast growth and breasts, they will need to get screened the same way as cisgender women. There was a study done in the Netherlands that showed that transgender women had a 46-fold higher risk of breast cancer compared to cisgender men in the population. So that just goes to show why it’s important for us to be screening people.

Another surgery that more and more transgender women are having is what we call “bottom surgery.” It’s a genital reconstruction or vaginoplasty. So, creating a vagina. There are different ways to do this. Sometimes the surgeons use an intestinal graft. So, they’ll use a graft sigmoid colon to create part of the vagina. There’s a possibility of developing vaginal polyps or even adenocarcinoma. It’s so important that clinicians know this because we do recommend that you do a visual inspection around the same time that you’re screening someone for colon cancer.

There are many different areas of primary care that providers need to know. You also asked about bone health and cardiovascular health. In general, someone living with HIV, you should be following the current guidelines for screening that you use for cisgender people. There are a few differences. If someone has had a gonadectomy, they’ve had the ovaries removed or the testes removed, and especially if they’re not taking adequate doses of their hormones or they’ve stopped altogether, then you need to pay very close attention to bone health. Screening for osteoporosis much easier.

As far as cardiovascular health, that’s tricky. There’s so many unanswered questions about that. Obviously, you should be using statins according to the guidelines. But there’s a question about whether you should be using a male or a female sex marker in the risk calculator. So, the conversation is still going on, and providers use different approaches. I think it’s a little bit beyond today’s discussion, but some clinicians will run it both ways, run it with an “F” and then run it with an “M,” and figure it somewhere in between. Some people will always use “male” in order to ensure that people are getting the care that they need, meaning earlier initiation of a statin.

So, there’s a lot to learn in this field, and we’re still doing the research and trying to come up with the answers.

Chris:
I always learn a lot listening to you, Asa, so really appreciate that.

I did want to mention that although the DHHS transgender guideline was removed from the US government site, it is on the Australian HIV guideline site. It’s not being updated, so there may be some things that are a little out of date there, but it can be accessed there.

Are there any other go-to references that you recommend? We’ll put those in our show notes.
 
Asa:
I think the HIV primary care guidelines for people living with HIV is a strong document and it has a section on trans people and HIV. definitely look at that. I think it’s a must read. If you’re generally focused on as an HIV specialist, how can I provide hormone care to clients because I’m learning that this is essential to keeping people engaged in care. There are many documents. UCSF has a website and primary care for trans folk, and it’s got guidelines on how any clinician can initiate hormone therapy. It’s really easy. It’s like the 101. Fenway Health also published guidelines and of course WPATH, which is the World Professional Association of Transgender Health. has a very lengthy document, but it’s more than just prescribing hormones. It goes into sexual health and reproductive health and many different areas. It’s a great go-to, but maybe just read the sections that you need. It can be quite daunting if you’re trying to read from the first to the last page.

Chris:
Thanks so much, Asa. I’ve enjoyed our conversation and learned a lot from you, as always.

Asa:
Thank you so much for inviting me. I think this was a great conversation.

Chris:
To our listeners, thanks for joining another episode of Viremic. Please send any comments or questions to viremicpodcast@jh.edu.

We’ll be back in two weeks with another episode. Thanks for listening.

Announcer:
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.

Viremic’s case discussions are for informational purposes only and 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 only, not an endorsement

The podcast is produced and edited by Mary Beth Hansen and Brian Hatcher with assistance from Jesse Ciekot and Laura LeBrun Hatcher.