Viremic – Cases in HIV

Case 16 Transcript

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, Eileen Scully.

Dr. Eileen Scully:
Welcome, everyone, to Viremic. Today, I’m excited to welcome our guest, Dr. Shauna Gunaratne. She is an Assistant Professor of Medicine in the Division of Infectious Diseases at Columbia University Medical Center and the Associate Program Director for the Infectious Disease Fellowship Program. She has clinical interests including the management of people living with HIV and also prevention of HIV, sexual health services, and general infectious diseases. She is one of those who loves everything about infection, which I totally identify with as well, [and she] also has done training in tropical and travel medicine and is actively involved in fellow and resident education. Dr. Gunaratne, we had similar training patterns—both training up in Boston before landing in our faculty locations. I would love to hear your best pitch for any listeners who might be considering joining what is, in fact, the best specialty, infectious diseases.

Dr. Shauna Gunaratne:
Hi, Eileen. Thank you so much for having me today on the podcast. So excited to talk to you. And yes, why is ID the best specialty? Well, if the last few years haven’t convinced you about what makes our field really interesting, engaging, and diverse, it’s always different. There’s always something new.

I’m particularly interested in emerging infectious diseases. That keeps us on our toes because we’re constantly learning and teaching ourselves and then get to teach our colleagues about new and interesting infectious diseases that become mainstream. So, I think it’s a really important field. We’re at the cutting edge and there’s always something new and interesting. Hopefully, that appeals to a lot of young people and trainees who are considering ID as a specialty.

Eileen:
That really resonates with me. In reflecting on what you’re saying, it’s that idea of beginner’s mind—we get to have that almost all the time with the endless possibilities and new things that pop up in infectious diseases. I love that. And I’m ready to join. In fact, I already have. With your particular interest in emerging diseases, I think that will fit quite well with our case for today.

This is going to be an amalgam of some patients that I’ve seen over the last few years, and I’ll just jump right in, and then we can have a discussion.

This is a 33-year-old man who’s presenting for evaluation of a rash. He has been living with HIV for about 8 years, has periods of both suppression and viremia, which is dependent on his level of engagement in care. Most recently, he had some family stressors, had not been on any antiretrovirals for about 5 months prior to the current presentation. His CD4 count prior to the interruption in care, the last data that we have when he comes in, was over 300. He had low-level viremia at that time, about 250 copies, and his status for his virologic markers, at least, is not known today.

He’s coming into clinic reporting a flu-like syndrome with fever, some body aches, and then a new rash shortly thereafter. The rash is on his hands and his feet, as well as some other locations on his body. It started a few days prior to his presentation. The flu-like syndrome was a day or so before that. Denies any nausea, vomiting, diarrhea, dysuria, cough, shortness of breath, or upper respiratory congestion—none of the other generalized symptoms that we sometimes see. Has not noted any lymphadenopathy.

He reported recent sexual contact with a man, most recently about 2 weeks prior to the onset of his symptoms. He reports that his partner was someone he did not know well, but to his knowledge was not sick at the time. He is quite nervous about the possibility of a sexually transmitted infection, and that is one of the reasons why he’s presenting today.

On exam, he had normal vital signs, and his only abnormal finding was scattered skin lesions. The largest were about 3 millimeters in size and appeared somewhat vesicular. At the time of presentation, they were scattered on his hands, including the palmar surface, but also on his legs, inner thigh, and multiple around the knees.

I’m going to pause here in the story to hear your initial thoughts and what your differential would be for this type of presentation.

Shauna:
It sounds like he has some sort of systemic illness, but what jumps out is the rash—that’s what’s bothering him the most, that’s what he’s presenting. It sounds like it’s not localized, but scattered all throughout his trunk, more on his appendages, legs, and hands, and vesicular in nature.

Thinking about his exposures, what prominently features is that he was sexually active about 2 weeks before the onset of his rash. So, we have a clinical syndrome of fevers, myalgias, and a diffuse vesicular rash, with recent sexual activity.

Thinking about who he is as a host, it sounds like he’s on and off antiretroviral therapy. We have a recent CD4 count of greater than 300. But despite that, he’s not virally suppressed. So, I’m concerned about opportunistic infections and just infections in general and someone who’s not virally suppressed.

So, my differential—I’m thinking about a sexually-transmitted cause of this diffuse vesicular rash, but we want to make sure we’re thinking about non-sexually-transmitted causes as well. What first comes to mind—syphilis at the top of my differential. It doesn’t sound like the classic textbook presentation of syphilis—the macules, the hyperpigmented reddish, purplish, brownish on the palms and soles—but a syphilitic rash can look like anything, and it can very much look vesicular. So, I’d be worried about secondary syphilis.

I would also be worried about mpox in someone coming in with fevers, myalgias, and a vesicular rash. [Note that the terms mpox and monkeypox are both used to refer to the orthopox viruses discussed in this episode.] Mpox, similar to syphilis, can look like anything—can look pustular, can look vesicular, can look macular, papular. So, I’d be wondering about mpox as well. With the sexual activity, wondering about a disseminated gonococcal infection, though he’s not having any arthralgias.

That would be my differential for sexually transmitted infections. If he wasn’t living with HIV, I would be thinking about acute HIV as a presentation. It doesn’t sound like the classic viral exanthem that we see, but if he wasn’t already living with HIV, definitely something that I’d want to make sure I consider.

And then non-sexually-transmitted causes with a vesicular rash in someone who has unsuppressed HIV, we’re thinking about herpes zoster, and so could he have a disseminated VZV? It sounds very possible given the description of the rash being vesicular in multiple dermatomes.

Eileen:
Well, that’s a beautiful differential. Thank you for starting us off in that way. I love the approach of considering first sexually-transmitted infections because common things and his level of anxiety about it certainly makes it necessary that we address that whether or not we think it’s leading, but also adding in the other systemic level non-sexually-transmitted infections that we could consider. So, I’ll give you some results of testing.

We did screening for syphilis [which], as you said, [can] look like anything, whenever you hear palms and soles, hard to avoid. His RPR was 1 to 8, but that’s actually serofast for him and stable over time. He had negative chlamydia/gonorrhea, testing from urine and throat and rectal swabs. He had a swab from the lesion that was negative for VZV and negative for HSV, which was checked also, though it would have been quite an atypical presentation, and did have positive testing for orthopoxvirus.

This case originated from a few years ago when this was probably a bit of a more common presentation, but I would love for you to start with talking a little bit about mpox, the outbreak from a few years ago, and the current status of ongoing transmission and how you think about approaching testing for it in your clinic.

Shauna:
Mpox jumped to the forefront of most infectious disease physicians, and general practitioners, in 2022, when we had the outbreak of the clade 2B virus that originated in West Africa and Nigeria and then spread through many countries, many of whom had never seen mpox before.

It had a different presentation and seemed to be predominantly transmitted through sexual contact or very close contact. So, in 2022, we saw a lot of mpox cases, and New York City was one of the epicenters of the outbreak of mpox within the United States. We saw a lot of cases, especially in the summer of 2022, but I think that was evidence of effective public health messaging during that time—there was a lot of public health campaigns and a lot of information being shared among populations that were at higher risk for mpox.

We luckily had a vaccine against orthopoxvirus, against vaccinia. That was also effective in being rolled out, and as a result, we were able to blunt the cases. We had a peak in the summer of 2022 and then cases dropped off dramatically as people altered their behavior, and vaccine rates increased.

Also, people were aware of what mpox looked like, were testing for it, and were appropriately counseling people on isolating. So luckily, we haven’t seen a peak like we had in 2022, but mpox hasn’t gone away. Even though we’re not hearing about it as much, we’re still seeing a lot of low-level community transmission, even in the last few months. Certainly in New York City, we’re still seeing cases. So, it is something that we want people to be aware of and make sure that you’re thinking about if you’re seeing someone with a compatible clinical syndrome and risk factors.

Eileen:
Just before we got on this podcast, I pulled up the New York state data, and it looks like there were about 375 cases in 2022, and then 2023 – 42, 2024 – 55, and then up through October of 2025, slightly higher rate than had been seen previously at 43 cases already for the year. So exactly as you’re saying, where there was this outbreak and now there is still sporadic cases of transmission and not among travelers. Again, something that we need to keep in our differential, in particular for those with the risk behaviors that were associated with transmission of this clade.

Now let’s move a little bit from what we learned about in terms of the classical clinical presentation and what makes you think to test for mpox and even how you approach testing, because it’s not the same. Many of the listeners were probably very comfortable with 3-site screening for standard bacterial STIs, but orthopox testing can feel a little bit more intimidating.

Shauna:
Yeah, so who to consider? The classical presentation of mpox with clade 2B, the groups that we think of at risk, in particular men who have sex with men or those who identify as other genders but are having ongoing close sexual contact.

You might have seen the pictures—it’s this umbilicated, deep seated lesions, multiple lesions around the body. But again, it can look very heterogeneous. It can start off as just a macula and then progress, become papular, vesicular—that pustule that we think about that we see is very classic for mpox—and then eventually scab over. It may not necessarily be [a] diffuse rash, or diffuse lesions like in the case that we talked about, but some people just have one or just a few isolated genital lesions. We have to be aware—it may not be in areas that are very visible.

If a patient’s coming in reporting a genital lesion, even just one isolated genital lesion, that’s something that we should be thinking about. For some patients, especially in 2022, not all of them may have visible lesions or a visible rash. Let’s say they have proctitis, for example—they may very well have anorectal lesions that we can’t see but are causing a lot of pain and symptoms. The complete absence of a rash doesn’t necessarily mean that someone doesn’t have mpox, especially if they have risk factors for mpox and they have a compatible clinical syndrome, such as proctitis.

About testing—use swabs to swab. Usually, the newest lesions have the highest yield of being positive. We swab the outside or the edges of the lesion. It’s important that it’s not required to unroof the lesion or use needles or aspirate fluid, those are not necessary and that increases the risk of the provider injuring themselves with one of these sharps. So just use a dry swab, not cotton, but a dry swab to swab the newest lesions. For the examples that we’re talking about, someone who might have proctitis, who may not have any visible lesions, then you can use a rectal swab, and send that off for orthopox virus testing. Some institutions have orthopox virus PCR testing in-house, but otherwise, you can work with your local [public health] state departments to send off the swabs for testing.

Eileen:
I’ll just mention that we’ll put in the show notes a link to the CDC guidance in how to conduct mpox testing, including precautions that should be used to prevent transmission to healthcare workers, which is a concern, although it was not a feature of that original outbreak. Really remains more of a theoretical concern, but one that we can easily manage with safe practices, and so we should.

With that in mind, have you been testing people currently? And as you mentioned, the absence of rash doesn’t necessarily rule it out. What are the kinds of scenarios in which you would order a test or try to pursue a diagnosis in the absence or presence of other symptoms?

Shauna:
Yes, we are testing for it. And just a few weeks ago had a case where the person didn’t seem to have very obvious risk factors but had a compatible clinical syndrome and the rash was very consistent, and the swab was orthopox virus positive. So definitely, if you are seeing someone coming in with genital lesions, even if it may not look classically like mpox, if you have a leading alternate hypothesis, I still swab them for mpox just because, again, they could have multiple things.

Even if it looks herpetic, for example, and we think that it’s HSV, the thing about some patients with mpox is that they can have bacterial or viral super infections. So, they could have HSV, but they could have mpox underlying as well. So, making sure that we’re not anchoring on one diagnosis if someone’s coming in with a genital lesion.

For my patients who are coming in with proctitis, if I don’t see any overt lesions, I don’t necessarily swab the rectal area for mpox, but I would treat them empirically, and if they are not improving or still having persistent symptoms, that’s when I’d think about mpox. Given that the pre-test probability for mpox is a little bit lower than, for example, if I was seeing that person back in 2022, mpox would be much higher on my differential.

Eileen:
And just to clarify there, when you say treat empirically, you mean treat empirically for bacterial proctitis causes?

Shauna:
Yeah, for gonorrhea and chlamydia/LGV.

Eileen:
Now let’s talk a little bit about once you have a confirmed diagnosis and the options for interventions. When do you consider them, which patients? And then maybe we can talk a little bit about how the concurrent diagnosis of HIV factors into those treatment decisions.

Shauna:
Back in 2022, we were using an antiviral called tecovirimat as part of an IND protocol. And then there was the Stomp Trial, enrolling patients in the United States with clade 2b mpox, looking at whether tecovirimat was beneficial. Unfortunately, it did not show benefit in in the treatment of mpox lesions. So, we no longer are using that for patients with mild to moderate mpox. There was also a trial, POM007 in the DRC looking at not clade 2B, but clade 1. Tecovirimat didn’t show a benefit there either. So, it doesn’t seem that tecovirimat, at least by itself, is helpful in the treatment of mpox, so, we don’t offer it.

Most people with mpox who have relatively suppressed HIV on antiviral therapy, it’s a self-limiting disease and they’ll just get better with supportive care. Where I would think about offering specific antiviral treatment is in someone who has unsuppressed HIV, very low CD4 count, and we’re seeing a much more severe form of mpox. It’s been well described as a opportunistic infection when it presents with a severe necrotizing form. So, someone like that, we’d be thinking about antivirals because the risk/benefit is a little bit different than the patient population that has been studied in these trials. There, we’d offer a combination antiviral therapy. So tecovirimat plus cidofovir or brincidofovir in someone who has a severe necrotizing form of mpox.

Eileen:
To put some of this in context—for the vast majority of individuals for this clade of infection, it was a self-resolving illness, and the goal of treatment was to reduce the number of lesions, reduce the frequency of new lesions. These are hard endpoints to meet, so, it’s not shocking that an antiviral wouldn’t work and that it wouldn’t necessarily be recommended for all of those who have mild disease.

We will put in the show notes the multi-country case review series that amalgamated case reports, with a very structured case report sheet from more than 19 countries between May of 2022 and January of 2023, where they looked at individuals who were living with HIV over 18 years with a CD4 count less than 350 or stage C disease if no CD4 counts were regularly available. They reported the results from 382 cases that met these criteria, who had a diagnosis of mpox.

Within that cohort, they did identify a subset who had severe complications, either necrotizing skin lesions, severe lung involvement, or secondary infection and sepsis. Among those, 28% were hospitalized, and one quarter of those who were hospitalized died. That was definitely in the group of individuals with more advanced immunocompromise. All of the deaths occurred among people with the CD4 count less than 200. For those patients, antiviral treatment is still something that we would want to consider; survival is a much less soft outcome than faster resolution or a smaller number of lesions.

I think it is easy if someone has necrotizing skin findings or pulmonary involvement, but how do you identify someone who’s at the highest risk? There’s the obvious things like HIV count, but are there specific things that you include in your clinical evaluation or assessment of someone to stratify their risk for a severe presentation?

Shauna:
I think based on the cohort that you’re talking about that was published, especially thinking about their CD4 count and how long they’ve been off of antiretroviral therapy and also where the rash is. Specifically, areas where, it would be devastating, the eye, for example, or certain parts of the face, in the urethral area or rectal area, where if there’s a lot of scarring or fibrosis that could be debilitating to a patient. Also thinking about where the lesions are and their risk of developing the severe form of mpox.

Eileen:
So, to summarize, clearly not as common as it was at the peak of the outbreak back in 2022, but still sporadic transmission ongoing, and it can be difficult to identify with behavior screening those at high risk because basically having sex is a risk and that occurs in many people.

Testing when appropriate clinical scenario, even though we wouldn’t have thought about it before 2022, and paying some attention to HIV status in terms of the risk of severe disease, although using clinical indicators of the actual presentation, including location and then severity of the lesions or other systemic symptoms sounds like the general framework of an approach.

Shauna:
Yes, definitely. it’s important to note if you are seeing lesions that look textbook classic for mpox, but the person doesn’t have any risk factors, it’s still important to test because oftentimes people may not be forthcoming with their true risk or have a lot of stigma or other feelings associated with that. It may not be their risk, but if they are sexually active with one partner and that partner has other partners, then they could have transmitted. So, in many of these case series, a significant percentage of patients diagnosed with mpox only had one partner. It’s important that, like you mentioned, anyone who’s sexually active, even if they say, “I only have one partner,” it’s important that that still is a risk and that we test them despite them not, having traditional risk factors that we think about.

Eileen:
Yeah, exactly. And also, that destigmatizing approach to these are questions we ask everyone, these are tests we do for everyone because we’re not that great at identifying the people who are at risk and sometimes people aren’t that great at identifying themselves.

The one other thing I’ll ask you to comment on briefly is in that case series, there was some discussion of whether or not there was an IRIS-like phenomenon in a subset of the individuals who started ART around the time of their concurrent diagnosis with mpox. I’ll tip my hand here in that, with IRIS, with very rare exceptions like closed-space CNS infections, I view IRIS as, there’s only one way to get from immune-suppressed to immune-competent, and it’s something we have to go through, not something that we can avoid. There are some data for a couple of infections for reducing the antigen load with a period of treatment, but in general, that period’s quite short. I was wondering if you had any thoughts or comments. I don’t know that there’s a real evidence base to make a great decision about mpox and IRIS, and if it’s something you factor in with starting ART.

Shauna:
I’ve seen a couple cases of the severe necrotizing form, and we try to get them started on antiretroviral therapy as early as possible despite the possible risk of IRIS, just because besides the other antivirals that we may offer, we know that reducing their immunosuppression is key in getting control of the infection. I don’t think, in the couple cases that I’ve seen with possible IRIS, we haven’t actually used any immunosuppression to treat the IRIS—just continuing on with ART and then treating mpox with antivirals, vaccinia immunoglobulin.

Eileen:
I would agree. When you are in a situation where you’ve got an infection that’s opportunistic, meaning it can’t do its thing without the immune suppression, and the severe form does appear to have a tight correlation with immune suppression, whether it is HIV and advanced CD4 decline or transplant or other similar situations, you do need your immune system, turns out, and turning off HIV even before you have full reconstitution of the CD4 count does substantially improve your immune response. So, I would be totally in alignment with you on that practice.

Let’s talk a little bit about prevention. We’ve talked a bit about someone who’s coming in with lesions and about how people can come in with lesions. What is available for prevention? And how are you recommending it currently?

Shauna:
There is a vaccine that is widely available in the United States. The brand name is Jynneos. It’s a live form of vaccinia, but it is replication incompetent. So, you cannot get the infection from the vaccine.

We were offering it to people in 2022. Since then, there have been studies that have shown that it is effective in preventing mpox and also decreasing the severity of mpox. So, it’s still our most important tool in preventing mpox.

In 2022 and 2023, there was a lot of vaccine uptake and practitioners recommending the vaccine. It’s dropped off, but we are still seeing mpox cases. People who are at risk or anyone who’s sexually active should consider getting the mpox vaccine because we’re still seeing cases. Since 2022, while we have seen some breakthrough cases in people who are vaccinated, in general, most of the people who have developed mpox are those who have never received a dose of the vaccine. It is the most important thing that we can recommend to our patients who are sexually active to protect themselves against mpox.

Eileen:
So, it sounds like someone who’s coming to you regularly, for example, for HIV pre-exposure prophylaxis services, or someone who’s living with HIV who’s, for example, on doxy-PEP for knowingly engaging in higher risk sexual activities and wanting to do responsible protection, those would be people to definitely have this conversation with about considering JYNNEOS. The data about its effectiveness are overall reassuring—maybe you wouldn’t say this means you will never ever get this, but it does appear to have a good high level of protection. I don’t know if we know as much about the durability, although some of the studies that looked at people who had gotten the vaccine for military service did seem to suggest there’s a pretty long-lasting effect of some protection.

Shauna:
The CDC recommends giving it to people who are living with HIV, even not on antiretroviral therapy, if they are at risk. It’s also one of those vaccines where we don’t have to necessarily worry about CD4 count before giving the vaccine, especially if they’re at risk.

Eileen:
Back in 2022, a couple of my patients were quite interested in the vaccine, who were probably not that high risk, but who were quite educated and at the leading edge of preventive care. I feel like that population, we did a great job in. Reaching the younger people who might be at higher risk, who might not be reading about all the things they can do to maximize their health is another challenge and one that we can keep doing.

I did recently have someone come in with a suspect case and had not been vaccinated and [that] had me reflect on my practice patterns and think about whether or not I should have been discussing that at a more recent appointment. Ended up not being mpox, but did prompt a lot of that thinking for me.

Shauna:
Mm-hmm. Yeah.

Eileen:
One last thing I thought maybe you could comment on is, at the beginning of the podcast, you talked about how there was a wave, and you were able to blunt it with effective public health messaging. I was thinking about how that has not been the story for a number of things over the last few years in infectious diseases, and just to get any thoughts or reflections you have on why, in this case, with a population that does have some trust in the care that we provide, that we’re better able to deliver some of these preventive messages and to flatten the curve, for example, of that. Do you have any thoughts about that?

Shauna:
Yeah, It’s interesting. I think in the beginning, there was a lot of debate about effective public health messaging around mpox. There was even a lot of debate in the beginning about whether it was a sexually-transmitted infection or not. We know from evidence, from studies of different samples of lesions of different body fluids, that it is sexually-transmitted, but also not exclusively sexually transmitted that it, from close contact that doesn’t necessarily have to be sexual. But during the beginning of the outbreak, the public health agencies partnered with a lot of the populations that were at risk and were able to influence a lot of the messaging. So, it got to the people that it needed to reach in a non-judgmental informational way. And there were a lot of lessons learned from COVID and from other sexually-transmitted infections and from the HIV epidemic and messaging to at-risk groups. There was a lot of good partnerships between public health and community organizations and community groups to help influence the messaging so it would be most effective.

Eileen:
Yeah, I totally agree. It’s also an example of when patients are coming in asking for something that it’s always better than us trying to sell it, not sell it, but offer it and sing its praises when people have already come to the conclusion that this is something that they want, and getting information into the hands of people who can disseminate it from trusted advisors, is effective and was great in the case of this particular outbreak. I will just summarize what we’ve gone over today—think about mpox, is the top line here, it’s rare, but still occurring. That we have good testing, we have effective prevention methods, and we can have it on our differential for people who present with either a totally classic or a little bit of a confusing picture and work on stopping transmission so that this does not become a bigger problem for us than it has been.

Any other comments you’d like to make?

Shauna:
No, that was a great summary and thank you so much for having me.

Eileen:
Thanks so much, Dr. Gunaratne, for this great discussion, and to all of our listeners for tuning in. Please check out our show notes for helpful links about mpox and we will see you at our next episode.

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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.

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