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. Chris Hoffmann:
Welcome to Viremic. I’m Chris Hoffmann, coming to you from Johns Hopkins, and I’m joined today by my friend and colleague Eileen Scully. Before we start, if you like this podcast, please share it with a colleague and follow us wherever you access podcasts. In addition, we love hearing from listeners. Please send questions or future topic suggestions to us at viremicpodcast@jh.edu.

Eileen, it’s good to be back in Baltimore and discussing HIV care with you today after I’ve been away for a couple of weeks with travel.

Dr. Eileen Scully:
Welcome back to Baltimore, Chris. It’s fall here, my favorite time of the year. I think because I’m a nerdy student who likes the start of school.

Chris:
Well, hopefully we’ll have some good learning here. I want to talk to you about a recent new patient. He was scheduled with me for follow-up after hospital discharge. He’s a 30-year-old bisexual man who had about four to five months of respiratory symptoms that included a cough and some dyspnea at times, especially when he was working out, and about a 20-pound weight loss during that time.

Prior to the hospital admission, he had received several courses of oral antibiotics as well as a course of prednisone without really good control of his symptoms. Eventually, he was admitted to the hospital with worsening dyspnea. And, on admission, he was afebrile but developed a fever some while after admission but was notably tachypneic, and he was diagnosed with advanced HIV disease, his first HIV diagnosis.

His CD4 count was 34 and viral load was 160,000. He had an LDH [lactate dehydrogenase] of 391, a beta-D-glucan of 350. He did have an induced sputum, DFA [direct immunofluorescence assay] for pneumocystis, which was negative. And he had a chest x-ray, which was read as bilateral, right greater than left, diffuse consolidative opacities involving mostly the lower lung fields. A chest CT subsequently confirmed those findings with diffuse ground glass infiltrates. Other labs of note shortly after admission were a toxo IgG [toxoplasma immunoglobulin G antibody] that was negative; a serum cryptococcal antigen that was also negative; AFB [acid-fast bacillus] blood cultures that incubated for several weeks, but they were negative [for Mycobacterium] at 10 days; hepatitis B surface antigen was negative; and hep C antibody also negative.

I only met him after he was discharged from the hospital, but perhaps you can reflect on his presentation and interpret some of the labs that he had and provide some diagnostic and management considerations if you had been taking care of him while he was hospitalized.

Eileen:
Chris, this is a pretty common type of scenario, although one that we really do hope to avoid by identifying people living with HIV earlier in their disease course. I’ll just start off by noticing that he did have a couple courses of prednisone prior to his presentation, and we should keep in mind that those can suppress the CD4 count even further than it would be without the prednisone.

But regardless of that, his CD4 count of 37 is consistent with advanced HIV disease, and his presentation is highly concerning and specific for pneumocystis pneumonia. Now, you gave us a couple of tantalizing labs here, including an LDH of 391, that was one of our older style indicators of PCP pneumonia [Pneumocystis pneumonia], and a beta-D-glucan of 350, which is markedly elevated. But you also gave us a negative induced sputum for direct fluorescence antibody testing. So, this brings us to one of the questions around pneumocystis as a specific diagnosis.

LDH is considered indicative of the process, but it is a very nonspecific marker of cell death, so not really a great diagnostic for a particular pathogen, although clearly elevation is associated with PCP pneumonia. The beta-glucan, I find to be a very useful test, and this is useful primarily in that if it is totally negative; it makes a diagnosis of pneumocystis very unlikely. This is true in particular for people living with HIV, and the sensitivity of this test is less well documented in the population of people with immune suppression for hematologic malignancies or other causes. But if it is totally negative, that really supports [this not] being the diagnosis.

I will say that the negative DFA is useful in [that] it says something about the burden of organism, but for me, it does not exclude the diagnosis, in particular in the context of a very compatible clinical syndrome, which he has here. So, pneumocystis in people living with HIV tends to be a subacute presentation with cough, dyspnea, fatigue, and then more acute presentation actually driving the hospitalization, much less likely to be a sort of “Last night I was fine. This morning I feel terrible and short of breath.” And that is exactly the history that he gave us. His CD4 count puts him at high risk for pneumocystis, and his beta-glucan being elevated would be highly consistent with that diagnosis. And although this is something we treat with Bactrim, it is in fact a fungus, which is why the beta-glucan is elevated. Also combined with his chest x-ray findings, and presumably you didn’t mention this, but I’m guessing that other community-acquired pneumonia workup was negative, and he’s already had insufficient responses to standard treatments for community-acquired pneumonia.

Overall, this to me hangs together quite nicely as a pneumocystis presentation. I’ll also just mention briefly that, while we often think about ruling in or [ruling] out pneumocystis, the most common cause of pneumonia in people with advanced AIDS is still standard bacterial causes. This is why, as we talked about a couple of months ago, the pneumococcal vaccine is so high on our list of favorites. But in this particular clinical scenario, where there’s been a trial and failure of antibiotics, we do start thinking much more seriously about the opportunistic infections, with pneumocystis leading that differential.

Chris:
I think that was pretty much the approach of the hospital team. He was started on a combination of broad-spectrum antibiotics for bacterial pneumonia as well as trimethoprim sulfamethoxazole for pneumocystis pretty soon after admission. The broad-spectrum antibiotics were removed, as there was no clear indication of a secondary process or a bacterial pneumonia. Shortly after he was started on trimethoprim sulfamethoxazole, he became more dyspneic, and prednisone was initiated as part of the pneumocystis therapy. He was also started on bictegravir, emtricitabine, and TAF [tenofovir alafenamide] within a day or two of admission.

The hypoxia worsened a little bit after admission, although he was able to be maintained on supplemental oxygen and was eventually discharged about a week after admission to continue the standard three-week course of trimethoprim sulfamethoxazole and a three-week taper of prednisone along with the Biktarvy [bictegravir/emtricitabine/tenofovir alafenamide] for his antiretroviral therapy. And [he was] also discharged with supplemental oxygen, given intermittent hypoxia at the time of discharge. I first saw him about a week after hospital discharge, and at the time I saw him, he noted morning fevers that had only started after hospital discharge. They tended to improve when he took the prednisone that was part of his pneumocystis therapy. He also noted some worsening frontal headaches that were annoying but not so severe that he couldn’t concentrate when he did some work from home in the afternoons. Overall, he looked okay on exam and on interview. And as I said, he said he was able to work about half a day on work-from-home activities. So, at this point, how would you address this situation and what differential would you consider for his symptoms, specifically his apparent new fever and frontal headaches.

Eileen:
The plot thickens, right? As you mentioned, this is a very compatible clinical syndrome and diagnostic workup, although without diagnostic certainty. So, in some references, you will see that there is a push towards real specificity in the diagnosis, which would suggest that a bronch [bronchoscopy] for BAL [bronchoalveolar lavage] for identification of pneumocystis would be appropriate. I agree with the management of this particular patient, which is generally that things that look like a duck and walk like the duck are probably a duck. And a lot of hospitals don’t have easy access to bronchs just to confirm a very reasonable diagnosis. But that would be in the back of my mind as I’m now evaluating him for a possible continuation of the initial process versus a new secondary process. Just that little tiny bit of like, “I don’t have all of my—not to use too many ducks, but all of them are not perfectly in a row here because I didn’t actually identify the organism.”

That said, there’s a broad differential for what could be driving—now—fevers and frontal headaches. Top of that list would be a concern about meningitis, and in particular cryptococcal meningitis. His recent testing with a negative serum cryptococcal antigen is reassuring, as that is positive in the majority of patients, even prior to them developing meningitis. Also reassuring are features of his clinical presentation that you describe, of him being relatively fine, outside of those morning symptoms, with the interventions that he’s already on, but being able to work, for example. Headaches are very nonspecific and could actually just be an indicator of a fever. And that really opens up your need for consideration to basically the whole rest of the body. And as I say to medical students and residents, the beautiful and terrible thing about taking care of people living with HIV is that Occam’s razor does not apply. And you may have correctly identified pneumocystis, but there may be other things that still require definitive identification and diagnosis in order to adequately treat and manage them.

So, on the differential here is a co-occurring opportunistic infection, of which there are many already mentioned: cryptococcal meningitis, again, negative serum CrAg [cryptococcal antigen test]; [and] toxoplasmosis, which often presents with CNS [central nervous system] symptoms, although a headache would be relatively nonspecific for that. His toxo antibody was negative, and he is on Bactrim, which is an appropriate treatment for toxo. So that also [is] a little bit less high on the differential.

I would ask questions about whether he had new rashes as an indicator of HSV activity somewhere or whether he had any other new localizing symptoms, for example, abdominal pain. At this stage, we would also be likely to see the impact of some early immune reconstitution, which can lead to the unmasking of a previously existing infection. And what that means is immune reconstitution inflammatory syndrome (or IRIS) is something where you have an abundant or exuberant inflammatory response to a pathogen. That can be a pathogen you knew about already, or a pathogen that was present in the body but not manifesting symptomatically, in large part because there had actually not been a response to it.

And so, once the body is capable of responding, then you can start to see symptoms related to that infection. There’s also paradoxical IRIS, which is when you’re improving on treatment, but then with viral suppression, it seems to worsen, but that’s a worsening of the symptoms not a worsening of the process, again, because those symptoms are driven by a productive immune response. So, at this point, my differential would include new primary infectious causes of fever, a drug-associated fever, as that can be very common in people with low CD4 counts, in particular in response to agents like trimethoprim sulfa, or an IRIS phenomenon either to an infection that was previously unidentified or to the infection we know about, which is the pneumocystis in this scenario.

So, what were you thinking?

Chris:
I also thought very broadly, and at the top of my differential was IRIS and either paradoxical to the pneumocystis or an unmasking IRIS. I really wanted to make sure, number one, that I wasn’t missing a meningitis. His overall symptoms were reassuring, as was the negative cryptococcal antigen that he had during the hospitalization.

If his symptoms had been any different or if he had not been so highly functional despite having the headaches, I would have been much more aggressive for additional workup for meningitis. Really, what I focused on was whether there was an unmasking IRIS going on and I was missing an additional opportunistic illness or whether this was all related to his pneumocystis. And maybe a few comments just about IRIS and how I was approaching it.

First of all, IRIS, or immune reconstitution inflammatory syndrome, is just that: an inflammatory syndrome related to antigens that are either from an infection or noninfectious cause. Typically, IRIS symptoms begin within a week or 10 days after starting antiretroviral therapy, occasionally sooner, and certainly they can occur at a later time, months later, or for some types of IRIS, even a year or more later. His onset about two weeks after starting antiretroviral therapy seemed consistent with IRIS.

Then just a few other things. He, as you’ve already discussed, had a very low CD4 count, and a CD4 count less than 100 is typical for IRIS. And the lower the CD4 count is, perhaps the higher the risk of IRIS. And then a second risk of IRIS is starting with a high viral load, and his viral load, close to 200,000, is certainly in the range that I consider high.

And then finally, IRIS only occurs if there is immune reconstitution, which is marked by a rapid decline in viral load. I also then obtained viral load testing to see if truly his viral load was declining. If his viral load had not declined, I would be much more concerned about a non-IRIS event. And I just wanted to mention it’s really the decline in viral load that’s associated with IRIS and not so much [an] immediate change in the absolute CD4 count. So, I eventually checked his absolute CD4 count, but in the laboratory evaluation I did initially, I really focused on the viral load.

Maybe you can comment a little bit more on some of the biology of IRIS, Eileen.

Eileen:
Chris, that’s a great introduction, and I was really reflecting on what happens in the immune system when we initiate antiretroviral therapy and how we sort of scaffold the reasoning of explaining the time course for these symptoms.

When we think about CD4 recovery, as you mentioned, it’s 50 to 100 cells per year, although there’s usually an initial bump that’s a recirculation of cells that have likely been sequestered in lymph nodes after the initiation of ART [antiretroviral therapy], and then slow gains after that. We do sometimes see people with much quicker recoveries. Typically, those are in the context of presenting with a severe illness that probably also contributed to the suppression of the CD4 count. But as you also mentioned, the timeline for IRIS is much shorter than a couple of years, which is what is required to really get your CD4 count back to a healthy status. So, what is the etiology here? When we talk about CD4 deficiency, I think one of the things we imagine is that the CD4 cells themselves are what is responding to the pathogen. And that can be true, but it would take a very long time to recover both the numbers but also the many different types of CD4 cells. Each CD4 cell is specific for something, so you don’t just need more, you need a diversity of specificities in order to adequately respond to infections.

So that’s one thing that makes it relatively less likely that CD4 cells themselves are what is reconstituted and then leads to the control of the pathogen and to this inflammation that gets a little out of control. But that seems to contradict your other very well-validated point, which is that the level of the CD4 count is predictive of your risk of IRIS. So, if they’re not actually doing it themselves, why is the number of them so important? And here, what I would say is that it’s an index of the immune suppression more broadly, so it is the most reliable number for measuring the impact of HIV on the immune system. And also, CD4 cells are a central regulator of immune responses. They include populations of T-regulatory cells, populations of cells that help B cells in order to make good antibody responses, and populations of cells that directly interact with pathogens—as a sort of orchestrator of many aspects of the immune response.

When your regulatory system is down, there’s a lot of potential for things to go wrong. I think some of what we see with IRIS is that there’s a dysregulation of the immune response and that is related to CD4 deficiency but not only driven by it. When you decrease the viral load, you decrease the amount of ongoing stimulation of the immune system. With 100,000 viral particles, you’ve got lots of bits of HIV that are stimulating monocytes, all different parts of the immune system, all the time. And those monocytes then behave differently when they see a second pathogen. When you shut down the HIV, I always imagine it as like the immune system taking a deep breath and then being ready to encounter pathogens and having that be sort of their first encounter with the pathogen instead of already seeing HIV in the body and then seeing pneumocystis, for example. In that context, they’re much more likely to have a more robust response. Now that’s great if it leads to clearing the pathogen. It’s less great if it just drives a whole bunch of inflammation.

So that’s how I think about IRIS and how it is and isn’t related directly to the CD4 count. And I think the other place that this [is] reflected in is the risk of autoimmune diseases with initiation of ART. So tissue-specific autoimmune diseases, which are usually cell mediated, generally occur late—more than a year out from initiation of ART—and that would fit with the timeline of when your actual T cells are really reconstituted. But lots of these pathogens have IRIS phenomena that occur much earlier, and that I think is more related to shutting down chronic viral stimulation and relieving the innate immune system in a way that allows it to see pathogens. Does that make sense?

Chris:
Yeah, beautiful explanation. And some of those later IRIS autoimmune phenomena include thyroiditis and Graves’ disease and probably some other autoimmune conditions. As you said, it’s a different immunologic process, although still related to the reconstitution of the immune system.

Eileen:
Exactly.

Chris:
In thinking about this patient and the potential of IRIS, either paradoxical IRIS to the pneumocystis or an unmasking IRIS, it’s perhaps useful just to comment on some of the more common conditions that cause IRIS. First, dermatologic manifestations of IRIS are reported to be the most common in some studies. I’m going to focus on more systemic causes. And the first case reports of IRIS are actually related to Mycobacterium avium that came during clinical trials of zidovudine monotherapy. And since that time, tuberculosis, pneumocystis, CNS disease with cryptococcus, PML [progressive multifocal leukoencephalopathy], and CMV [cytomegalovirus] retinitis and Kaposi’s sarcoma [KS] are key other conditions that are related to IRIS. There are a few infections, like toxoplasmosis, CNS toxoplasmosis, that rarely have been reported to cause IRIS.

I had this list in mind thinking about what could be causing [an] unmasking IRIS if the symptoms that he was having [were] not from the pneumocystis. And just going through this list, I’ll just make a few comments about what sort of symptoms could be expected. So, if this was Mycobacterium avium–related IRIS, I would certainly expect fevers. And then, as you suggested, maybe some localizing symptoms from increasing lymphadenopathy, which he did not have, but certainly did not rule out that possibility. For CNS disease, certainly a mass effect or worsening persistent headache and decreased level of consciousness, which he fortunately did not have.

For CMV disease and CMV retinitis, fever is pretty rare, but loss of vision from the retinitis isn’t, and he had no visual defects. I did encourage him to see an ophthalmologist. Unfortunately, he was not evaluated while in the hospital. When I saw him in the office, I did a non-dilated fundoscopic exam, but that obviously has its limitations. He had no obvious evidence of KS dermatologically or in his oropharynx, but [that] certainly does not rule out organ involvement of KS. And that’s where I was at that time. I did talk to him a couple of days later, and the fevers were persistent, but overall, his symptoms were similar and he continued to be able to work from home about half of the day.

Because of continued concern about IRIS and persistence of the symptoms, I eventually sent him for a CT to look for worsening lymphadenopathy for either a suggestion of Mycobacterium avium–related IRIS or a lymphoma that had not been seen on initial imaging. The imaging findings were only notable for pulmonary fibrosis in areas that had the previous infiltrates and no change in his abdominal lymphadenopathy.

Any other reflections at this point, Eileen?

Eileen:
Well, Chris, I think that was a beautiful outline of how to approach this. And, I’ll just say that when we think about IRIS and the potential for an unrecognized source, that it really matters where you think that might be. The consequences of inflammation within the closed space of the CNS are much greater than those, like, for atypical mycobacteria where you might have some lymph node necrosis and enlargement but you’re not going to have profound altered mental status or risk of herniation.

So, as we tick through the list, I think it’s also important to evaluate each of those. Where are there closed spaces or spaces where there is very little tolerance for inflammation? And those are the spaces that I need most urgently to exonerate as a cause of IRIS.

Now, as you mentioned, IRIS itself is an apparent inflammatory response, not necessarily dangerous if it’s not in a space that is threatened by that, but it is possible that the underlying infectious process could actually have negative consequences. And that’s why, also, there is some role for diagnostic certainty, for making sure that you’ve identified whatever it is that is driving this and you feel confident that that is under control either by the immune system or by therapeutics. For example, for CMV, we would be thinking about valganciclovir. For MAC [Mycobacterium avium complex], we would be thinking about appropriate directed treatment for mycobacteria, etc., etc. That’s the other part, if there is an undiagnosed component, then we’re not actually treating it.

And then I’ll just rewind from that a little bit, which is to say that when we think about delaying ART or other interventions because of a concern for IRIS, the rationale there is typically that we think that we will reduce the antigen load. So, you have a certain amount of pathogen in the body. If you treat with directed antimicrobials, you can reduce the amount of that pathogen so that when the immune system wakes up and starts to respond, it is not an overwhelming signal. It’s a more manageable amount of antigen. Now that’s a theoretical but not totally unsupported approach. But it is necessary to consider that sometimes antimicrobials on their own really can’t do the job, and so that’s when we need to push through this inflammatory syndrome regardless and re-arm the immune system to effectively control the pathogen. If we haven’t started directed treatment, it’s possible that we’ll need antimicrobials for whatever is driving that. Does that resonate with you?

Chris:
Yeah, definitely. I think those are such important points, and I think this gets back to timing of antiretroviral therapy.

This patient was appropriately started very soon after admission, after HIV diagnosis in the hospital. Multiple studies have suggested improved outcomes with early initiation of antiretroviral therapy for most opportunistic infections. But as you pointed out, for some IRIS processes, we may want to wait until the antigen load is a little bit lower, and those are specifically those in the CNS, and really most notably determined from clinical trials, delaying initiation of antiretroviral therapy with cryptococcal meningitis, although for TB meningitis it is also standard to delay antiretroviral therapy initiation. Really for everything else, we accept that IRIS is very likely if their CD4 count is very low, at the start of treatment of both the opportunistic illness as well as HIV and just attempt to manage the IRIS as best as possible. And, as you’ve highlighted, make sure that there’s not an additional condition that we’ve missed.

Eileen:
Those are great points, Chris, and I’ll just mention that for those residents who are in the hospital overnight and are trying to start “early therapy” after identification of an opportunistic infection, keep in mind that the trials define that as around two weeks. So, you do not need to do it overnight. If you have someone who’s newly admitted with an opportunistic infection and untreated HIV, “early” definitely counts after morning rounds, and you can talk through all the specificities of that decision-making in the morning.

Chris:
For sure, very important point. Perhaps we can transition to treatment of IRIS.

Eileen, how do you manage a patient and help a patient through their IRIS, both in terms of their antiretroviral therapy and any adjunctive therapies that you use or try to avoid?

Eileen:
IRIS fits into that rubric that I often say to people with a new diagnosis who have advanced disease: that there’s a strong possibility that things will get a little bit worse before they get way better. But I do some preemptive counseling about the fact that there often is a period of discomfort after initiating ART, whether that’s some time-limited side effects from your new medications, typically resolving in two weeks, [or] whether that’s some fevers related to a drug that you’re exposed to, a rash, or some actual immune reconstitution syndrome. It’s often the case that people with advanced disease will have a bit of a bumpy course initially, so I do set that expectation for new presentations. With that in mind, there are a couple of things that we can do to try to manage the inflammation.

I push, always, in people with advanced disease to have diagnostic clarity, but assuming that that has occurred, then we have our directed antimicrobials towards any potential drivers that we have identified for this particular patient. We have that to reduce our antigen load and hopefully offload the immune system a little bit. And then we have immune-modulating therapies; the easiest and first-line recommended are corticosteroids. And it’s interesting, the case that you bring is a great one because it outlines something that doesn’t happen all that frequently, which is likely here, I’m assuming, since we don’t have another diagnostic offered: that this is a pneumocystis-related IRIS presentation. Probably one of the reasons why that’s less common than with some other pathogens is because, often, if you have more moderate-to-severe disease, you’re initiated on corticosteroids preemptively.

So, even before you have the chance to have an immune reconstitution inflammatory syndrome, and the duration of that can probably manage IRIS-type symptoms for many of the individuals who have a reconstitution reaction to pneumocystis, for others where addition of corticosteroids is not standard, we are more likely to see it [IRIS] emerge. And for them, there’s really more expert opinion–level recommendations for the use of additional adjunctives. So, corticosteroids are the mainstay of treatment for things like IRIS from Mycobacterium avium complex. You can use lower-level therapies like NSAIDs [nonsteroidal anti-inflammatory drugs] or just acetaminophen for relief of fever. And so, while they’re not really suppressing the immune response, they do relieve some of the symptoms of the inflammatory syndrome and can be quite useful in helping patients to just weather that part of the storm.

One other specific case would be for things related to KS or KSHV [Kaposi sarcoma–associated herpesvirus], and in those, there are some inflammatory syndromes which have more specific names, like KICS [KSHV inflammatory cytokine syndrome], but those can have more directed immunotherapy options, including things like IL-6 antagonists. And in general, we avoid corticosteroids for KS-related problems because there are some case reports of explosive KS-related disease after the initiation of corticosteroids.

I’ll just summarize that if you have severe or disabling inflammatory symptoms that you feel are unrelated to a new process and you have exhausted that evaluation, you can manage those either with NSAIDs, if they’re relatively minor symptoms, or for more severe symptoms that are affecting quality of life and also ability to heal, corticosteroids can be used to fully suppress them, with the asterisk that we do avoid corticosteroids in KS-related diseases.

Chris:
Very nice summary. And starting ART, typically with IRIS, there’s not a need to rush in the middle of the night to corticosteroids, with perhaps an exception of pneumocystis, where corticosteroids are included in management algorithms for people with moderate-to-severe disease. And certainly [we] want to be very cautious or avoid corticosteroids in some situations, most notably Kaposi’s sarcoma. There is additional guidance on management of IRIS and diagnosis of IRIS, both from the New York State AIDS Institute guidelines as well as from the DHHS [U.S. Department of Health and Human Services] guidelines that are useful. I think for most of us, the starting point is to try to use NSAIDs or acetaminophen to manage symptoms if there’s not a life-threatening situation of hypoxia or airway or other obstruction, and then only escalating to other therapies in the setting that NSAIDs or acetaminophen are not effective.

The last thing in terms of therapy I wanted to say is that stopping antiretroviral therapy is never the answer. Working with the patient to get through the symptoms while maintaining both the therapies directed against the pathogen that may be related to the IRIS, as well as maintaining the antiretroviral therapy, is really critical for their long-term success.

Eileen:
Totally agree, Chris. All of those recommendations, they’ll say something like, consider corticosteroids and, in parentheses, while continuing ART. Don’t forget that part. We do have to get through this.

Chris:
Indeed, and given that starting the antiretroviral therapy and the rapid decrease in viral load is part of what’s driving it, it could be a logical thought to pause the antiretroviral therapy, but that is never the answer, as you highlighted.

So, Eileen, getting back to this case, about 10 days after he had completed pneumocystis therapy, or maybe a few more than that, his fevers resolved, as did his headache. My conclusion was that he had fairly severe IRIS to the pneumocystis and there were no other opportunistic illnesses or other illnesses in the background. Fortunately, he’s done well since then and has had CD4 reconstitution and remains well on antiretroviral therapy.

Eileen:
Perfect. It sounds like he had that rockier time and then moved through it and hopefully will thrive and live a really normal life on ART.

Chris:
Eileen, this has been a great discussion, and fun. And, as always, I learn from you when you discuss some of the immunological aspects of disease.

Eileen:
Chris, I love thinking about this and also talking with you. I think one thing for those who are listening who are going to be the leaders of the future: we do need better predictors of when the immune system is going to behave this way, or when the antigen load is going to drive this type of response. This is one area where there’s a lot of cross-pollination with other parts of medicine where we, as the physicians, knock out an immune system and then we see some type of immune reconstitution phenomenon. So, I think this is an area that’s ripe for new minds to think about and to identify some markers that would allow us to more efficiently identify people at risk. The CD4 of less than 100 isn’t that great of a marker. And then maybe to target interventions that are a little bit more specific than corticosteroids. I think it’s an area where hopefully some new clinical science will emerge.

Chris:
That would be such a contribution to medicine. I hope to be using those tools sometime in the future. To our listeners, thanks so much for joining another episode of Viremic. Please send any comments or questions to viremicpodcast@jh.edu. We’ll be back again next time with a case about weight gain on antiretroviral therapy.

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