Announcer

Welcome to the Academy Exchange, HIV Today and tomorrow. In this podcast, we discuss the latest advances in HIV prevention care and treatment, as well as examine the societal and systemic issues facing people with HIV. Thank you for joining us.

Bruce

This is Bruce Packett, Executive Director of the American Academy of HIV Medicine and the host for this podcast, the Academy Exchange. We're talking about the state of HIV, especially in the U.S. domestically here in 2023, and all of the social, clinical, political and dynamic issues related to the HIV epidemic and where it is headed.

Today, we'd like to focus on a more clinical issue that inevitably interacts with the social aspects of HIV and some of the perceptions therein. And that's the issue of HIV related weight change. Now, when we talk generally about HIV and weight change, I think some of the more obvious representations of HIV/AIDS, particularly from those early years of the epidemic, is the figure of AIDS related wasting.

And when I think about maybe like a younger generations perception of the early epidemic and say, like media representations, I think about movies like Dallas Buyers Club, where you have these major actors performing roles as HIV positive people living in the days of experimental AZT and so on, and they're losing unhealthy amounts of weight to portray these characters.

And I really think that common representative image or paradigm of AIDS related wasting on net really adds to the stigmatization of HIV/AIDS. However accurate some of those representations may or may not empirically be, right? But with HIV today, listeners may not be surprised to hear that weight change. And while it's still a potential issue and consideration and clinical concern for those with HIV and for their provider, it's also a lot more complex than some of those early representations.

In fact, we change in HIV, probably more commonly happens in the opposite direction for a whole variety of complex reasons that we'll talk about today. So before I get carried away with my introduction of the topic, I want to introduce my clinical expert on the podcast today, who is Dr. Daniel Lee.  And Dr. Lee is a clinical professor of medicine at UC San Diego Owen Clinic.

He is a HIV primary care provider and has been taking care of people with HIV for almost 25 years. He's also the clinical director for the Pacific AIDS Education Training Center HIV Learning Network, and the Founder and Director of the Owen Lipid/Lipodystrophy Clinic, which is a subspecialty clinic focused on managing metabolic complications of antiretroviral therapy. He also developed the content and is the keynote speaker for the AAHIVM Workshop on Managing Weight changes and people with HIV for HIV providers.

And because of his clinical focus on this subspecialty of metabolic and lipidystrophy, he is really the thought leader. We need to speak with us on this on this topic. Dr. Lee, welcome to the Academy Exchange podcast today.

Dr. Lee

Great. Thank you, Bruce.

Bruce

Sure.   So in my introduction, I started talking about the complexification of the clinical issue of weight change in HIV over the years. And I think the most interesting place to start our conversation is just with what you see in your clinic, empirically. Are you seeing issues of HIV related weight change in your clinic, and what is the predominant clinical presentation or trends of that weight change if so?

Dr. Lee

Great question. I think that we see the spectrum of HIV related weight changes still in our clinic. I think in your introduction you mentioned about the fact that I think in the early days of HIV, we used to see a lot more of the severe weight loss that occurred with what we would call HIV related wasting. And so back in the day, we used to see people before they were HIV diagnosed, or perhaps at the time of their HIV diagnosis, they would have had a pretty significant weight loss that then perhaps led them to get tested for HIV.

And then we would then find out that they’re HIV positive and kind of go on from there. And so that's kind of one end of the spectrum in terms of seeing people with weight loss. And these days for several reasons, because I think we're doing a better job at diagnosing patients a little bit earlier. I think we're identifying people before they have that significant of a weight loss, for instance.

And so that that's kind of on one end of the spectrum. I think these days we are seeing much more the issue of weight gain, which is kind of unusual. I think most of my patients would not have thought that that as they get older or certainly as they lived longer with HIV, that that they would have to deal with more issues like obesity and weight gain.

And so these days, that's kind of what we're seeing more of these days. And it's with, we'll get into it, I'm sure. But there are some relationship with perhaps some of the HIV medications.

Bruce

So that's a great starting point for my next question, which is exactly, why is this happening? People think about weight gain as a lifestyle issue typically. But it's more complicated than that with HIV, right? So what do you see is those key contemporary causes of HIV related weight gain that you're observing so frequently in your clinic?

Dr. Lee

Yeah. So probably several things that are related to the HIV related weight gain. The first thing is that if someone just recently got started on antiretroviral therapy, it's not unusual that you may gain some weight. And this has to do with something we call the return to health phenomenon. In other words, when people are not treated with HIV, they tend to have a higher metabolism, which in other words, means that that their body is working harder to try to remain healthy.

But unfortunately, what happens is that the metabolism is sped up. And so the tendency is for people to actually lose weight. And so when you start HIV medications, what happens is you slow the metabolism back to normal and in that process of slowing the metabolism, whatever weight that someone may have lost, let's say they lost 10, 20 pounds before they started HIV medications, we can probably expect that they would gain 10 to 20 pounds after starting their HIV medications.

And so that's one of the causes we think is related. But that's kind of to be expected. The other thing I think that people don't always think about is the fact that many people, let's say, if they've lost quite a bit of weight many times, their diet may not be the greatest. And in the process of starting new HIV medications, they may still be worried about losing all the weight that they've lost, such that maybe their diet isn't the best because they've been really trying to gain weight.

And oftentimes it can be difficult for our patients to, perhaps change their diet, especially when they were worried about losing weight for a while. And so that's another cause of weight gain. Sometimes people are so sick that they're perhaps not able to exercise. And so sometimes it's just the simple lack of exercise that can cause people as well to lose muscle mass and lose weight as well.

So those are just a few things to think about as well.

Bruce

Sure. I wanted to talk about your diagnoses and observations in your clinic of HIV associated weight gain. What sort of things are you specifically looking for when you examine a client to be able to look at them and sort of come to the conclusion that maybe there's something going on beyond just, you know, lifestyle issues? So I guess what I'm asking is what are your diagnostic criteria for identifying specifically HIV related weight gain? How do you make that diagnosis?

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Speaker 2

Yeah, I think most of the time our clients are the ones that usually come to us with that concern. And so, first of all, I think that's really how most of the time we're a little bit more aware of the fact that perhaps there is some weight gain issues. In terms of other criteria, certainly, we follow the patient’s weight over time and during the COVID pandemic, I think because of the use of telehealth and video visits and telephone visits, we have not necessarily been following the weight that closely.

And so unless if a client is checking their weight at home, then they might have some idea that they're gaining weight. And what we've been seeing in the clinic is that people that we haven't seen for a while due to the COVID pandemic are now coming back into clinic and now we're doing their weights again. And now all of a sudden we're seeing that their weights are up.

And so I think during the COVID pandemic people were a little bit less active. And sometimes because of stress, maybe more stress eating those kinds of things. In terms of other diagnostic criteria, in terms of actually looking at, let's say, doing a physical exam, it's really the probably the abdomen size is probably the main thing that many of our clients may come to us noticing that maybe their belly size has gotten bigger, their waist size has increased, their clothes don't fit or they fit tighter these days.

And so those are some of the other questions that that, you know, we can ask and I think clients can kind of pay attention to. So, for instance are your clothes fitting tight or is it harder to get into, putting on your belts or even putting on a bra? Those kinds of things?

So from a diagnostic criteria, I think mainly looking at the belly, we can also look at arm circumference and waist circumference as well as like leg circumference. And sometimes we can also make determinations related to weight based on those as well.

Bruce

Sure, that makes sense. And I'm interested in how this weight gain sort of affects the health of that client specifically as it relates to HIV, because I think most listeners will well, sort of generally understand that during the pandemic, a lot of people pick up extra weight, having a higher body mass index, with or without HIV, carries with it risks and health complications.

I'm interested in hearing what weight gain specifically means for an HIV patient. So in other words, are those clients who do in fact have HIV and are also gaining weight, have special clinical considerations or risks associated with that waking up?

Dr. Lee

Yeah, and I think with those clients who are who have HIV, that the excess weight gain can lead to other what we call co-morbidities, other disease states, things like high blood pressure, diabetes, and both the high blood pressure as well as diabetes as a result of weight gain are not necessarily good things because we already suspect that those with HIV may have this accelerated aging process that I think we all theorize as that happens in people.

And our concern is that if there if people are gaining weight, that's leading to more high blood pressure, diabetes, as well as things like higher cholesterol levels, all of those things are heart disease risk factors. So that actually puts our clients at risk for perhaps earlier heart disease, earlier risk of stroke as well too.

Bruce

Right. And obviously we haven't really got into the idea of the treatments themselves causing any sort of weight change. You know, the antiretrovirals used to keep HIV in check as being one of the possible causes of weight gain in HIV patients. And I'd like to dig into that a little bit, because we really want to make sure that certain unpleasant or unwelcome side effects of the HIV treatment don't lead a patient to disengage with their HIV therapy or with their adherence to the medication.

So first, what do you see as sort of the mechanism of that weight gain associated with antiretroviral therapy? How does that come about?

Dr. Lee

So I think right now the mechanism of the weight gain is still something that researchers and clinicians are still trying to understand. So there isn't an exact mechanism of action that has been determined yet. But there have been associations with specific antiretroviral therapy. More specifically, the integrase inhibitors. But even within the integrase inhibitors, probably more the newer what we call second generation integrase inhibitors, Bictegravir as well as Dolutegravir. Those two of may have probably been implicated a little bit more than some of the older integration inhibitors.

And then the other medication would be tenofovir alafenamide, otherwise known as TAF, and that is a nucleoside medication. And that has also, there have been some reports in people that suggest that being on that regimen may increase the risk.

But I think in terms of the actual mechanism, there have been some theories about, with the integrase inhibitors having perhaps a direct effect on fat. And apparently in some studies, if you actually look in fat, you can find that the medication can actually get into fat, which is different perhaps than other classes of medications. But for the TAF mechanism, unfortunately, I don't think we really know at this point.

Bruce

And what can you say about options for providers and those clients who may be concerned about the meds themselves leading to weight gain or there are there are mitigating things they can do to prevent that weight gain. Or maybe it's a case where they might consider switching the kinds of HIV medications they're taking to help with some of those weight gain issues.

And I'm thinking about PrEP, too, because we have that TAF that's half compound in one of the PrEP options. And I'm wondering if it might be an option for them to consider a different medication in that case.

Dr. Lee

Yeah, great questions. I think in terms of mitigating things to try to prevent weight gain, I think ultimately that our general recommendations for everyone across the board is to try to do as best as they can in regards to increasing physical activity and getting exercise, but also working on your diet. And so if the diet isn't ideal, then of course that may increase your risk of weight gain.

I should make the point that that this weight gain doesn't occur in everyone. So, you know, I don't want everyone to all of a sudden say they're going to stop all their HIV meds. I certainly don't want that to happen. But it does seem to occur more in a smaller subset of patients that maybe are more on the outliers.

So what I would say is that out of, let's say, 100 people that are taking these medications, I would say about 80, 90 of them probably are going to do fine without any issues. But maybe it's those ten people or so that may have some weight gain and it can be on the order of 5 to 10 pounds.  But there have been reports of some people where it's been more dramatic, like 20 pounds.

Some of the risk factors in terms of who they're seeing this more in. There are some risk factors. So it does seem like we see more of this weight gain in people of color and so more in African-American patients as well as Latinx patients. We've seen that more. 

We've seen it as well, more in women than men. And so as to why this is the case, I think this is still to be determined. And so some people have tried to, I think, warn people who fit in those categories, perhaps to maybe much more closely watch their weight when starting antiretroviral therapy of any sort.

But I think to kind of get back to your question, certainly things like diet and exercise are still the ideal things to do. And I think closely watching your weight over time and certainly talking with your provider, if there are any questions in regards to concerns about weight gain. To answer the question about switching medications or not, there have been some early studies that have looked at possibly switching the integrase inhibitor out or perhaps switching the TAF out.

And I think in some cases there appears to be maybe a little bit more success with switching TAF out than the integrase inhibitors in terms of improving weight. But I will say that the amount of, let’s say, the weight improvement or weight loss that you might see with switching to something else has been only partial. So it isn't like you can lose everything that you've gained.

And so maybe there is some benefit. But officially, the recommendations from the many different guidelines that exist do not suggest that you switch antiretroviral therapy due to the lack of data at this current time. 

I think your last question was in regards to weight gain with PrEP, and I think that that that absolutely is potentially a concern for those people who are on PrEP. But in my review of the data, it appears that the weight gain is not as significant from my own personal experience with my own patients on PrEP, with these agents. But there are reports that weight gain has occurred in people on PrEP. I think ultimately, whether we're talking about a PrEP setting or an HIV treatment setting, I think you always have to balance the risks versus the benefits of these agents.

And for the most part, I still think that the benefits of, whether it's the integrase inhibitor or a TAF containing regimen, still oftentimes outweighs the downside of the weight gain that might potentially happen.

Bruce

Yeah, that's a really, really important message that I just want to underscore for our listeners. And I'd like to switch gears here and go back to what we were kind of referencing at the beginning of our questions and in the introduction, which is the clinical phenomenon of HIV related weight loss or even wasting, as it's often known, is this something you can vouch for empirically?

Are you seeing or hearing about cases where there's actually weight loss or HIV associated wasting here in 2023? And what's the latest understanding of that phenomenon?

Dr. Lee

You asked the question and it sounds skeptical as if does this really occur? And it's great that you ask that because I think that the common misperception is that, yes, we do not see it anymore. Like, why are we even talking about this? But I think it's a very valid question. And I work in both the outpatient setting as well as the inpatient setting and I still do see some of the more severe wasting syndrome like we used to see back in the early, for me, 90s.

But those are few and far in-between these days, unless you actually work in the hospital. Most of my colleagues work and they outpatient setting and it's rare that you'll see someone who has HIV associated wasting like how it appeared back in the early days. The presentation of wasting, however, these days is, I think, a little bit different in the sense that those people who may have evidence of wasting and weight loss in my practice tend to be older individual who have probably been HIV positive for many, many years, let's say 15, 20 plus years.

And I think that in these people, the main thing that they notice is perhaps decreased weakness, or I should say increased physical weakness, and perhaps decreased physical endurance. So the ability to do activities of daily living sometimes become a bit harder. And it may be because they're starting to lose muscle mass. And so when you're losing more muscle than, that can be a sign of wasting.

Bruce

Sure. You kind of touched on this, but what is this complex of reasons why we're continuing to see some of this HIV associated weight loss they're wasting? I mean, obviously, we have these really effective compounds to treat HIV. Right? And what we're seeing in the metabolic clinic is this weight gain typically, it's really kind of a marker of our successes, like you mentioned, a return to health in treating HIV in staving off some of the worse complications. So what is behind the ongoing existence of HIV related weight loss?

Dr. Lee

Yeah, I think I think it's as I alluded to earlier, I think this has to do with probably an accelerated aging process that we see in people with HIV. And so what I would say is that the longer someone has had HIV, the more amounts of inflammation that someone has. So I can back up for a quick second.

Is that, we know that HIV itself is a condition that is associated with inflammation. And inflammation, I guess, in a in a more basic way of explaining it is kind of like when your body is fighting against an infection, it can create these chemicals as kind of a byproduct of fighting the infection. And these byproducts can cause other effects on the human body.

And HIV is a condition of inflammation. And the longer that you've had HIV, the longer or the more inflammation your body has probably seen over, let's say, 15 or 20 years. And I think cumulatively, that length of time of inflammation can affect the physical body in different ways. And one way is basically manifest in accelerated aging.

So our patients with HIV do seem like they age a bit quicker. And in other words, what we are seeing are things like high blood pressure, diabetes, liver disease, kidney disease, heart disease that occur at slightly younger ages compared to people without HIV and without that amount of inflammation.

Bruce

Sure. And it's a great point that you made earlier as well. And I wonder what clinical interventions you see as the most fitting to address weight loss and wasting. How can providers be more vigilant in looking for is screening for HIV related weight loss when it's the weight gain that seems so clinically predominant?

Dr. Lee

Yeah, that's a great question. And it's I think it really has to do with both providers as well as patients being aware that this can possibly happen. I think that we really do not think much about weight lost, sorry, weight loss these days because things are being a little bit overshadowed more by weight gain. Plus, I think, in the U.S. where obesity rates are a bit higher.

And so many times the obesity and the weight gain issues tend to kind of block out the weight loss that might be existing. So I think it's important for providers as well as our clients to ask themselves or ask their patients questions such as are you noticing having more difficulty with doing things on a daily basis So it can be as simple as bathing, cleaning of the house, walking to the store, getting groceries.

Just very basic things. And if the answer is yes, that there is an issue and that and someone is having more difficulty, then it's absolutely worth notifying their provider that something is going on and perhaps initiate some evaluation for weight loss.

Bruce

Right. Yeah. This is all been such really, really interesting information and we're really lucky here in this decade, in this time, to be in a place where we can really talk about and find food, a patient's overall health. You know, to the extent that we're addressing BMI issues and just a more general sense of overall wellness.

It really is a testament to an index of how far we've come with some of these early images of people with HIV losing dramatic amounts of weight and getting sicker and sicker. So even the fact that we're talking about this, I think, needs to be contextualized more broadly in the sense that we have been very successful in changing the course of HIV to where we can really focus on overall wellness and a kind of human flourishing.

Any final take home messages or conclusions around, wait, changing HIV that you'd like to offer listeners today?

Dr. Lee

Yeah, I think just reminders of trying to maintain some level of physical activity. So from my standpoint, I really try to advise my patients as they start to get older. And so probably around the age of 40, I'm starting to counsel many of my clients about the importance of working on increasing physical activity and exercise at an earlier age.

And it's really just because it really becomes much harder to do it as you get older. And I know that for a fact because I have my own challenges trying to get out there and exercise myself. And so I think it's especially important for those with HIV, really to start to develop a habit of exercise early.

What that does is, is help you to build up muscle and thus prevent problems of wasting and weight loss, which can then impact one's ability to perform whatever activities and do the things that you want as you get older.

Bruce

Yeah, that's right. And it's even a great message for everyone, I think. Dr. Lee, it's been a pleasure today. Thanks again.

Dr. Lee

Great. Thank you very much.