Viremic – Cases in HIV

Announcer:
Welcome to Viremic–Cases in HIV, a podcast that explores quandaries in adult HIV clinical care. In each episode, Drs. Eileen Scully and Christopher Hoffman, 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 are your hosts, Eileen and Chris.

Dr. Chris Hoffmann:
Welcome to Viremic. I’m Chris and I’m joined with my friend and colleague Eileen. Good to be talking to you again today, Eileen.

Dr. Eileen Scully:
Great to be speaking with you too, Chris.

Chris:
What case do you have for us today?

Eileen:
I was reflecting on my clinic just the other day and on the conversations that come up most frequently with a particular group of patients who are doing fantastic on their therapy and what kinds of concerns they have. So today’s case is going to focus on the people who are doing really well on their antiretroviral therapy and thinking about how to optimize things in a way that is a privilege to be able to do. So you ready?

Chris:
Go for it.

Eileen:
This is a 48-year-old gentleman. He comes in for routine care. He’s seen in the clinic roughly every 6 months. He’s had full viral suppression for many years and is stable on a regimen of bictegravir, emtricitabine, and tenofovir alafenamide. He has no noted side effects, and he doesn’t have any challenges with adherence, just takes it when he brushes his teeth, no problems. His other medical history includes glucose intolerance or pre-diabetes and hypertension, for which he’s on hydrochlorothiazide and losartan as 2 separate pills, and on that regimen has had good control.

He has a family history notable for an aunt with kidney disease who’s on dialysis, a father who had cardiovascular disease in his late 60s and early 70s, and a sister who had thyroid cancer but is doing really well.

He has no known drug allergies and has never had any surgeries.

He works in information technology. He’s married and has 2 children. His wife is also HIV positive. He has a history of tobacco use in his 20s, but only about 5 pack years, and he quit many years ago. He drinks alcohol 1 to 2 times per month and only 1 to 2 drinks per occasion, and does not use any recreational drugs, and has a pet dog at home.

Recently he started listening to some podcasts about healthy living, and he’s interested in thinking about how to work on other aspects of his health outside of just going to the doctor every 6 months. Specifically, he’s been focusing on his diet and exercise at home, and he’s also been looking into supplements.

At today’s visit, he wanted to discuss the immune boosting effects of supplements and whether or not his medications themselves, the ones he’s taking for either his hypertension or for his HIV, could be causing health problems that he should be conscious of. He’s wondering if he’s on the safest possible regimen, and he’s interested in whether or not he could reduce the amount of medications that he’s taking.

As a starting off point, Chris, where do you begin this kind of a discussion with a patient?

Chris:
As you said, it’s always wonderful when HIV is in the background and general good healthy living is in the foreground. A few observations about this patient: He is getting close to middle age depending on how you want to define that. Often people may have increased weight gain, more difficulty with starting exercise or returning to exercise, and increased risk for a variety of cancers—prostate cancer, colon cancer—that we do routine screening for. I don’t know about this gentleman’s prior sexual practices, but he may be at increased risk also for anal cancer.

I start with congratulating the success with his adherence to his antiretroviral therapy regimen and that he will be able to continue to do well in terms of viral suppression and probably not have any complications from living with HIV, and then move on to some of the considerations with HIV. One big one is often the immune deficiency related to HIV. In my patient population, it’s often those people who’ve been living with HIV longer and perhaps lived through a period of complications of profound immunodeficiency.

I think it’s helpful to reassure somebody with normal CD4 count that they are pretty close to having a normal immune system. That sometimes can go a long way in terms of the conversation of living well with HIV.

Eileen:
Well, I love the way that you approach that, Chris, and it really is in line with what I do as well. When someone comes to you with questions about adjunctive treatments or other things that they can do outside of what is normally prescribed within a medical office, my first stop is to validate that and say, absolutely, we’re going to talk about all of those things. But my second is to go through all the things we have really strong evidence for already.

As you mentioned, age appropriate cancer screening, all of these other things for which we have rigorous data to suggest that they can improve outcomes and make sure we’ve checked off all of those boxes because that’s not the patient’s job. The patient doesn’t need to stay up to date on the latest recommendations from the United States Preventive Task Force or other such bodies. That’s our job.

And our job is to lay out the whole menu of options for medical-based interventions that we can do to optimize outcomes. Once we’ve done that, then we should turn back to the behavioral things that people can do. I love when people come asking questions about that because they’re expressing that they’re in a space where they’re trying to optimize. It’s a great time to address all the preventive health maintenance and then also to think more closely about what other things they can do with behavior or supplements or other approaches to try to maximize their health.

I’ll mention briefly a patient who taught me a great deal, who had tremendous difficulty taking her antiretroviral therapy, although she did not have difficulty coming to appointments, so she would come regularly and just never take her medications. We spent a lot of time crafting crushable or liquid medications because we thought that there was a barrier related to pills and actually to swallowing pills.

Then, at some point, I think it was more than a year into us being in a doctor-patient relationship, she mentioned that she took several vitamins, which were large pills that she swallowed every day. It was so eye-opening for me in thinking about what goes into the things that we choose to do and the things that we choose not to do and what either the health beliefs around her antiretrovirals or the stigma associated with taking antiretrovirals was doing to modify her behavior in that specific domain.

That’s just a side note about thinking about what people do for their health from a supplement perspective can sometimes give you some insight into the barriers to what they’re able to do for their health in other ways, for example, in taking their medications.

But to bring us back to this question of immune boosting and thinking about immune system function, I tell people living with HIV who have full viral suppression that they can count on their immune systems, in particular when they’ve been fortunate enough to have immune reconstitution up to numbers that are approaching or exceeding those of people who do not have HIV. We do think that there are a lot of ways in which their immune system is very robust.

There are a few instances in which we still have some concern or we treat them slightly differently in thinking of them as a potentially immunocompromised population, but it would be more on par with the immunocompromise that goes along with many other conditions. Well-treated diabetes, for example, and maybe even less severe than that. Other health conditions where there’s a modest impact on your immune function, but nothing like the susceptibility to opportunistic infections that we see with advanced disease.

As you are, I’m generally very encouraging about what I think the immune status is for those individuals who do not have great immune reconstitution of their T cells, but do have long-term suppression of viremia. I also think we can give a lot of good news. In general, viral load suppression improves the function of the immune system, even in the absence of full reconstitution of CD4 T cells. So those people I also provide some reassurance to, basically reminding them that suppressing the virus has taken so much pressure off the immune system that the cells that are there are just able to function better. They’re not as robustly protected as people with normal CD4 counts, but they still do have a lot more protection than individuals without full viral suppression. So as you, Chris, I reassure people a lot about this.

But in particular, in the COVID-19 era and moving forward, there’s been lots of talk on social media and in the news about immune boosting—what are the things that you can do to make your immune system function better than it would otherwise? I think the short answer to that, and here putting on my hat as an immunologist, is that there really is not much data to suggest that any supplements or particular approaches lead to, quote, better immune function.

In general, healthier living, getting all of your nutrients, having access to all the vitamins and minerals that you need to be a healthy person definitely improves immune function. But whether or not someone who has a diet replete in those things has additional benefit from taking supplements is a bit questionable, with a few exceptions. So when people start to talk about immune boosting and taking supplements, there are a couple of things I generally keep in mind.

The first is to think about supplements as medications, and I encourage people to consider them as things that they’re taking that could interact with their other medications and that could also have side effects, because a lot of the marketing around supplements doesn’t really mention those things, and it can take people by surprise that these things they think of as just like eating extra blueberries might actually have interactions with other things that they’re taking.

The classic example for this is St. John’s Wort, which was very popular more than a decade ago and recommended as a treatment for many conditions, including depression and wound healing. But it does have a potent inhibition, or potent effect on one of the drug metabolizing enzymes, and it specifically can lead to drug-drug interactions, including with reduced efficacy of protease inhibitors. So that’s one to always ask directly about.

In the modern era, with integrase inhibitors, we always have to think about the divalent cations and absorption of integrase inhibitors. It’s well known that dolutegravir (all of the integrase inhibitors) can be chelated in part by divalents, so plus 2 cations that are present in the stomach, and this can lead to lower levels of drug exposure. This is neutralized if you’re eating a meal. So if you take your vitamins, eat a meal and take your medications, that’s generally fine. But if you take your magnesium supplement and your bictegravir at the same time, you’re at risk of having a slightly lower absorption of your bictegravir.

Chris, how do you counsel your patients about vitamins?

Chris:
All great points, Eileen. I have patients who, for one reason or another, want to take vitamins or other boosters for immune function or for general cognitive function, strength, weight loss, or other factors. And I often am actually learning from them. I have a number of patients who get a lot of their information from TikTok. So I try to learn from them what the trends are on TikTok or other media platforms. And then we look online to see where interactions are or ask them to send me a picture of the product through the patient portal and provide them some feedback.

I do counsel in the same way that you do and recommend a reasonable balanced diet. And I’m happy to either review that with my patients or I refer them to dieticians. Also I’m big on exercise. And for many of my patients when I mentioned exercise, their first thought seems to be sweaty gyms and lifting free weights. I try to reassure them that that is a good form of exercise, but just going out for a walk and encouraging this patient with his dog to maybe take longer walks, as I think that’s a great form of exercise. And as you highlighted already, the divalent cations, iron, magnesium, calcium, I will specifically call those out and ask patients if they’re taking those to review the drug-drug interaction with absorption for integrase strand transfer inhibitors.

Eileen:
Chris, we have the same prescription for exercise. I also have the same speech, which is exercise is walking and not expensive gym memberships. We also talk about safe places to walk and how to do that in climates that can vary. Here in Baltimore, it does get quite cold in the winter, which can be limiting and also dark early, but in the summer, it can be just as limiting with how hot and humid—it feels like swimming instead of walking. But there are a number of indoor shopping malls, which can be a great place to walk. If you’ve ever been to them early Sunday morning before they actually open, there’s plenty of people who are in there getting a couple laps around and some good exercise. And they can fit in some stairs if they have time as well.

So I agree with you that exercise should be an increase in activity level, walking to where you might be a little bit out of breath having a conversation with a friend and trying to pair it with something you really enjoy doing, listening to your favorite episode of Viremic or your favorite music or talking with a friend, something like that, so that you’re more likely to keep doing it. And in his case, I agree, pairing it with his pet is a great approach.

Also because it’s been a hot topic in the last year, with the measles outbreak, there was a lot of discussion of the use of vitamin A. Vitamin A has been shown in public health studies to have some efficacy in preventing the serious complications of measles, but the bulk of these studies were performed in places with higher rates of nutritional deficiencies. So it is a recommended therapeutic as an adjunctive during management of measles infection, but it’s not a substitute for prevention in any way and doesn’t provide protective effects against actual infection with measles, just does hopefully provide some benefit in terms of preventing serious complications.

With vitamin A, we’ve also seen that with use of supplements, people should reach out to their providers and talk about them. I have the same approach as you do. I have people tell me the name of it in the office. Oftentimes, they will have a picture of it on their phone, and we’ll look it up together on the internet and go over what the ingredients are and what we think they might be doing. And in general, I will run them through there are a number of supplement interaction checkers that you can use, and there’s also information on the NIH website. There’s an Office of Dietary Supplements at the NIH that has a fact sheet for many different kinds of supplements. And the FDA also has some great information about different supplements, what’s included, and how to judge whether or not they might be beneficial.

In general, with respect to supplements, I encourage people to try to get as many nutrients as possible from their actual diets, just as you do, Chris, trying to encourage a broad array of colors on the plate, which tends to ensure that you’re getting more different kinds of vitamins and minerals. This is in part because the absorption is a little bit better in the context of a normal diet and also because supplements can be quite costly. And there are often questions about the composition, and there’s differences in the rigor of FDA oversight of supplements as compared to pharmaceuticals.

Okay, now let’s turn back to our patient’s other question. He’s going to exercise more. He’s maybe going to take a vitamin, but not going to spend his whole paycheck on supplements, and nothing that we’re concerned about interacting, and he’s going to space it out from his Biktarvy. So let’s turn back to the question of whether or not any of the medications he’s taking are putting him at any risk of harm, and whether he’s on the optimal regimen for who he is now as a 48-year-old man.

First, we can address his antihypertensives. If he’s been on a stable regimen of these 2 medications and his insurance is amenable, he could potentially be put on a combination pill of this regimen. This might have some psychological benefits in reducing the burden of the number of pills, so that would be one place to start. I don’t think that there’s very strong data for combination of 2 pills into 1 for improved adherence, although there’s definitely good data for multi-dose versus single-dose. So taking it once a day only is definitely better. But I do think for some people, having 3 pill bottles or 2 pill bottles does actually make a difference. So that might be one place to start.

Second, let’s take a look at his HIV regimen—bictegravir/emtricitabine/tenofovir alafenamide.

First, we can pause here and talk a little bit about whether or not you’re a change-er versus a stay-er in HIV care. I think we all have a few patients who are on what would be called an old-style regimen, and whether or not you change them depends a little bit on both the patient and the provider. Chris, what’s your general approach to people who are doing well on a regimen? Do you offer changes? Do you discuss it each time? Or do you sort of let things ride when they’re going well?

Chris:
It really depends on the patient. Some of my patients are very wedded to regimens that they are on, often because of side effects and treatment failure earlier in their history of HIV. It depends a little bit on the regimen. If the regimen, even if it’s an older regimen, seems to have no clear side effects and no clear advantage of switching, then I typically will leave the patient on that regimen.

There are a few agents that I really try to get people off of. Those include abacavir, lopinavir, ritonavir, and some other older protease inhibitors. In addition, I tend to prefer dolutegravir or bictegravir over raltegravir, although I have patients on raltegravir. And even just recently was discussing with one of my patients on raltegravir along with the rest of the regimen, whether he wouldn’t prefer to be on a once-a-day integrase strand transfer inhibitor. He told me, no, he was very comfortable with taking raltegravir twice a day and just made it part of his routine. So that’s my approach and discuss it frequently with patients, but often we don’t make any changes.

Eileen:
Chris, I agree with all of those things in your approach and that the patient is in the driver’s seat unless there’s a clear contraindication to the use of a particular medication or a new adverse effect or a new comorbidity has arisen that would change how you’re thinking about a component of the regimen.

The one other medication that I’d add to my list of things I try to get people off of is Etravirine and that’s not because of any specific side effect of the medication itself, but rather because the relatively complex drug-drug interaction profile that can happen with etravirine. It is again a case where if someone is stable on it and they have other medications that I think are partially balanced by it, are interacting with the metabolic pathways that etravirine is also interacting with, but are at stable and good levels, I might leave it alone. But if someone is basically on no other medications, I do like to get rid of it because it can be a little bit of a challenge to manage and that drug-drug interactions are a little bit unpredictable.

I’ll also mention briefly that, in general, people who are on etravirine have also often ended up on it because of a history of resistance. So it’s always worthwhile in those particular individuals to look back in their treatment history and think pretty carefully about how they ended up on that medication and what their options would be for the most modern possible regimen that would still maintain viral suppression.

I’ll give you a little bit more history about his HIV before we come into a real decision about what to do with his regimen. He was diagnosed about 15 years ago. His CD4 count at that time was over 400. His viral load untreated was 65,000. And his baseline protease and reverse transcriptase genotype was without any resistance mutations. He was fully suppressed initially on a regimen of efavirenz/emtricitabine/tenofovir disoproxil and then changed to rilpivirine, emtricitabine, and tenofovir alafenamide. This was then updated to bictegravir, emtricitabine, TAF, which he’s on now, over the last 5 years. This was due to some minor challenges around the meal requirement for full absorption of the rilpivirine-based regimen. He just didn’t feel comfortable always having to eat in order to feel like he was getting his medication in.

In the 15 years, he’s had a few blips to viral loads of 55 to 80 copies/mL, but otherwise has had full viral suppression, and his CD4 count now is up in the 800s. So with that history—really well treated, well controlled HIV with excellent adherence—let’s talk a little bit about what each component of his regimen is doing.

The classical framework for highly active antiretroviral therapy was 3 active drugs, but this has shifted substantially in the last few years, and now we have a number of 2-drug regimens. They include dolutegravir and rilpivirine in a combination oral pill, cabotegravir and rilpivirine in an injectable regimen, dolutegravir and 3TC in a combination single pill. And we also have evidence for darunavir boosted plus 3TC as a 2-drug combination, although we do not have a U.S. formulation that only has those 2 medications in it.

With all of these regimens, what’s the first thing that you have to do before we make any kind of switch, assuming that we were going to actually make a switch?

Chris:
Yeah, I think as you pointed out, classically, triple therapy was the way to go with HIV treatment since 1995, with studies that for the first time showed durable viral suppression. It’s useful to mention that there have been multiple 2 and 1 drug regimens that have been studied in RCTs over the last 20 years. Many of them did not pan out so well, either because of early virologic failure, because of increased metabolic complications, or because of virologic failure in long-term follow-up. Those include NRTI-sparing regimens such as lopinavir/ritonavir plus efavirenz, atazanavir/ritonavir plus efavirenz, darunavir monotherapy, darunavir plus raltegravir, maraviroc plus a boosted protease inhibitor, and going even further back, dual NRTI therapies.

I think it’s useful to keep in mind that even if something seems like it may be a good idea, without really good clinical evidence in an uncontrolled setting, if there are other options with demonstrated effectiveness, it’s always best to go to those. And that is the approach I take. Moving on from that, it’s hard really to beat Biktarvy or bictegravir/emtricitabine/TAF. I do like Odefsey or rilpivirine/emtricitabine/TAF as well; and it sounds like this gentleman had some concerns about being able to always take the pill with a meal, as is recommended with Odefsey.

I do have conversations about potential benefits of fewer agents. I think one of the things we know about these agents is that they’re safe and there do not seem to be long-term complications. But that said, the fewer drugs that somebody needs to take, probably the better over a long period of time.

Eileen:
We’re aligned in many things and also the therapeutic nihilism of if you don’t need it, don’t take it. I agree with that. It does come into a risk-benefit analysis of what you’re getting out of dropping additional medications. So specifically, before you make any of these switches, I’ll just briefly remind the listeners that dolutegravir, rilpivirine, and CAB/RPV were initially approved and studied in registrational trials for switch therapy only, not for initiation. As we know, there’s an emerging literature of post-marketing studies looking at cabotegravir/rilpivirine for people with viremia in select settings, but in general, the approval for these agents is for people with full suppression.

Dolutegravir/3TC has been studied as a new initiation, 2-drug single pill regimen with good results. So that makes it a bit different from those other two. But with all of these switches, as you say, it is hard to beat bictegravir/ emtricitabine/TAF. One of the reasons is because TAF and tenofovir formulations in general have been shown to have higher efficacy than other NRTIs, and trials going back many years now, and also give the added protection against hepatitis B.

So whenever considering changing to a 2-drug regimen from a 3-drug regimen, it becomes critical to confirm the hepatitis B status of the individual in front of you. This is because we sometimes can have individuals who have hepatitis B who’ve had no complications, haven’t shown any signs of having the illness, but are fully suppressed on a tenofovir-containing regimen. With withdrawal of that regimen, they can have rebound hepatitis B viremia and hepatitis that can be severe. So for anyone who you’re considering changing to a 2-drug regimen, make sure that you have good, accurate data about their hepatitis status.

In this case, they returned as hepatitis B surface antibody positive and core antibody negative. That’s a status consistent with vaccination and full protection. So we can move ahead with discussions to consider losing the tenofovir component.

The bottom line here is that we do have other options. If an individual is committed to having the least possible exposure to medications, then I think for someone with this profile, dolutegravir/3TC or even dolutegravir/rilpivirine would be a perfectly fine option and would give them a high likelihood of maintaining viral suppression and no additional risk. The rilpivirine, we’re going to hesitate on because he’s already expressed that he has some challenges with taking with a full meal. That would push us more towards cabotegravir/rilpivirine as an option for that combination of medications with an injectable delivery. Separate discussion with him on whether or not he’d like to come in once a month or once every 2 months, as opposed to what he’s currently doing, which is once every 6 months.

Dolutegravir/3TC would be a great option also. No anticipated loss of suppression, full susceptibility based on his baseline genotype and long-term viral suppression. Then we would have eliminated exposure to tenofovir. As we know, tenofovir does cause a modest reduction in bone density. It is substantially less with the alafenamide preparation, and it’s also less than the amount of bone density reduction you would have with untreated HIV. But this is a side effect of the medication.

There is some small risk of renal dysfunction, again, much lower with the tenofovir alafenamide, but still present. And as you say, taking any medication has some risk of side effects, and possible to reduce it, that might be an incentive for some people.

It would just come down to a discussion with him. How do you feel about it? We’re not changing the number of pills you need to take. We would be changing the number of components in those pills. Is that attractive to you? Is that not attractive to you? I do feel like we have strong data for either of those approaches, and they could be recommended with equal vigor for the patient. And whatever his preference, I would be happy to move forward with it.

I’ll mention one exception to 2-drug regimens is a lack of data in pregnancy. For women of reproductive age in general, maintaining them on regimens that are safe for conception and 3-drug regimens is recommended during pregnancy. Although if someone becomes pregnant, that becomes a separate type of discussion.

Chris:
Yeah, totally agree with all of that. He is a reasonable candidate for a switch to a 2-drug regimen. He lacks any of the key risk factors for failure in many of the clinical studies, which is a viral load greater than 100,000 (his viral load was 60,000 or so, you said) and a low CD4 count, less than 200 at ART initiation and his CD4 count was, I believe, over 400, you said. Then finally, baseline HIV drug resistance. It sounds like he did have baseline genotyping and no resistance was identified. So he’s in the population from clinical trials that have done well on 2-drug regimens, and if he wanted to switch, I would discuss that with him.

Any of the regimens you mentioned is reasonable. I have quite a few patients on dolutegravir plus 3TC, and that would be a reasonable regimen. Obviously, as you mentioned, if he prefers an injectable regimen, we have cab/ rilpivirine also to offer to him.

Eileen:
The thing that has pushed me to take people from 3 to 2 drugs has typically been changes in kidney function. He does have a history of pre-diabetes. He’s got an aunt with kidney disease. No baseline renal function issues, but if that were to change over time, that might be an indication for which I would say, let’s just get the TAF off the table. Not because we can’t use it, but because it can sometimes just be a little cleaner to not worry about whether or not that’s causing any additional renal injury. But otherwise, I’m not convinced that there’s data to support superiority of 2 drugs over 3 drugs, but we do have good data to support equal efficacy. That’s where I generally leave it with patients now, is a shared decision-making conversation, just like the one you described.

Chris:
On any given day, a patient like this coming to see me may continue on bictegravir/TAF/emtricitabine, or we may decide to switch to dolutegravir/3TC.

Eileen:
After you make a switch, in the older days, we would always check to make sure that we had maintained viral suppression. I have yet to have an individual who changed in this type of situation and then lost viral suppression in the last, I would say, 10 years. But in general, my practice is to check a few weeks after the change to ensure that there’s stable safety labs and also that we’ve maintained viral suppression. What’s your practice on that, Chris?

Chris:
Very similar, or maybe I’m even less forceful in getting patients in a switch like this back for viral load testing. Usually we’ll want to test within 3 months of a switch and then going back to every-6-months testing simply because of my experience of not having had any problems.

A different scenario, which is a conversation for another time, is when I try to simplify extremely complex regimens that were started prior to the availability of some of the agents we have now and prior to the evidence we have on simplified regimens. Then with limited, often limited drug resistance data. I get them in very frequently for some number of months to repeat viral load testing before I’m confident enough to switch to every-6-months viral load testing.

Eileen:
I agree, we take the same approach in that situation, and I will preview that at one of our other podcasts we will talk about that more challenging situation where you’re taking something that’s working but it’s onerous and trying to switch it to something that will still work but is a little bit more palatable and maintainable for the long term.

Thanks so much for all your thoughts about this case today and as I said it grew out of a conversation I had with a couple of patients yesterday and really just made me reflect on how nice it is to be talking about optimization of health for people living with HIV and just so happy to be living in a time where we have these amazing opportunities to really tailor therapy and to maximize the health of people living with HIV and how we want to keep working to make sure that there’s equitable access to that type of treatment for everyone globally who lives with this.

Chris:
Definitely, and thanks so much for sharing this case with me, Eileen, and thanks to all the listeners for your time today. Really appreciate it.

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

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

Visit the program’s website at HIVguidelines.org.

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

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