How effective is HIV treatment today? What sorts of side effects do they cause? Dr. Joe Eron addresses concerns and questions related to HIV medications in this HIV Matters episode. He explains how they work in the body, and describes the latest research being done to improve treatment. Dr. Eron is Professor of Medicine and Vice Chief of the Division of Infectious Diseases.
鈥淭he therapy now is, for almost every patient who comes in who is newly diagnosed, they can be treated with one pill once a day. It鈥檚 a combination pill鈥攊t鈥檚 got multiple medicines in it, but it鈥檚 one pill once a day. All pills have side effects鈥� but they tend to be pretty mild. Literally, I tell people- ‘If you take it, you will respond.鈥�
鈥� Dr. Joe Eron <!– –>
Specific Topics Covered:
- Talking about fear and stigma
- Starting treatment for HIV
- Consequences of not taking medicines
- How long it takes the drugs to work & how they work
- Commonly asked questions about HIV medicines
- Current research in HIV treatment
- Changes in HIV outlook over the last twenty-five years
Ron Falk, MD: Hello, and welcome to the Chair鈥檚 Corner from the Department of Medicine at the University of North Carolina. This is our series for patients where we talk about HIV. In previous episodes, we discussed PrEP, we鈥檝e talked about getting clinical care for HIV, and today we will focus on treating HIV.
We welcome Dr. Joe Eron, who is a Professor of Medicine and Vice Chief of our Division of Infectious Diseases, and while he looks remarkably young, he has a very long history of treating patients with HIV. Welcome, Dr. Eron.
Joe Eron, MD: Thanks for inviting me. This is really going to be fun.
Talking about fear and stigma
Falk: When you have a patient who has recently found out that they have HIV, and you鈥檙e about to begin treatment, what kinds of thing do people talk to you about? What concerns do they have?
Eron: Well, I think there鈥檚 still so much misimpression or bad information about HIV. Patients still come in thinking, I鈥檝e got a fatal disease. I鈥檓 going to die from this. That鈥檚 the most common thing.
Falk: In 2018, that鈥檚 amazing.
Eron: Right, in 2018. I spend a lot of time talking to them about how they鈥檙e actually going to live. We have therapy that鈥檚 pretty straightforward. It鈥檚 not that hard anymore. I really try talk to them about what they鈥檙e going to do in their life to change what鈥檚 happened that got them into this situation, but lots of times I have people who have been infected for years sometimes and they鈥檙e just diagnosed鈥攁nd they鈥檙e devastated, and they鈥檝e kind of moved past that part of their life. They鈥檙e devastated. They think, I鈥檝e escaped from my bad behavior or risky behavior from ten years ago, and then they think, Oh my God, I didn鈥檛 escape. I can鈥檛 believe I have this. So, dealing with that fear, that I鈥檓 going to die. The other thing is, I can鈥檛 possibly let anyone know.
Falk: Embarrassment.
Eron: Embarrassment, stigma鈥攅xactly. Those are the two biggest things鈥攖he fear of the disease itself, and the fear of being isolated and just not being able to let anyone know about what鈥檚 happened to them.
Falk: In reality though, the therapy is remarkably good.
Eron: Right. The therapy now is, for almost every patient who comes in who is newly diagnosed, they can be treated with one pill once a day. It鈥檚 a combination pill鈥攊t鈥檚 got multiple medicines in it, but it鈥檚 one pill once a day. All pills have side effects as you know, but they tend to be pretty mild. Literally, I tell people- 鈥�If you take it, you will respond.鈥� The issues are really getting people to take it. It sounds like, 鈥淥h anyone can take one pill once a day for near fatal disease,鈥� but it鈥檚 not so easy.
Falk: Right.
Eron: So, they need to take the pill, and if they have a problem, they need to communicate and say, 鈥淭his isn鈥檛 working for me.鈥� But most people do pretty well.
Falk: How do you help with the stigma issue?
Eron: The stigma issue is a lot harder. It鈥檚 funny, there are data that suggest if someone comes to their first HIV appointment with someone else, they do so much better, because they鈥檝e already been able to tell somebody something. So, for dealing with the stigma, I ask them if there鈥檚 someone they can bring to their appointment with them, someone I can talk to鈥攁 partner, brother, sister, a parent, or a child鈥ut I think the stigma really is a huge problem.
Falk: Having an advocate though, regardless of the disease, in the room with you is always a good idea.
Eron: Yes, for anyone listening to this podcast, that鈥檚 one piece of medical information, anytime you encounter the health care system, to have someone who鈥檚 an advocate who can listen with you, because鈥 hear half the things you say. I try to hear the good things you say, but it鈥檚 stressful, it鈥檚 hard, you don鈥檛 know what people hear when you talk to them. Having another set of ears there makes a big difference. It really helps.
Starting treatment for HIV
Falk: When should someone with HIV start treatment? Is there a magic moment?
Eron: There used to be a magic moment. We used to argue all the time about which stage of disease should we start treatment, and in part it was because we were worried that one, our treatments in the past were more toxic than we wanted them to be鈥攖hey had more side effects.
The other thing is, we worried that the virus would become resistant, so we would wait. That鈥檚 pretty much over. Mike Cohen, who works with both of us, helped show that really, starting therapy as early as possible is beneficial to patients. We try to get people on therapy within one or two visits after seeing them. There are places in the country where they鈥檙e starting treatment at the patient鈥檚 first visit, because there鈥檚 some evidence that if you give people a therapy, they can embrace it鈥攖hat this is a serious illness, this is something I should be doing, why wait? We don鈥檛 wait now. We start right away.
Falk: First visit.
Eron: First visit鈥攊n our clinic, it鈥檚 usually the second visit, because we have to organize how they鈥檙e going to get their medicine, to make sure their insurance is together. We might need to use our Ryan White program, which is a federal program that helps patients get medication. So, it鈥檚 usually the second visit we start.
Falk: The fear of resistant virus. Is that completely gone away?
Eron: No, it鈥檚 not gone, but it鈥檚 diminished. We鈥檝e studied this in our clinic pretty carefully, and you can see the proportion of patients with resistance declining over time, but there is transient resistance. Some patients show up, having been infected with a virus that鈥檚 resistant, but for the most part, we can deal with that very, very easily.
Falk: With other drugs.
Eron: With other drugs, right. We get a resistance test at baseline so we can check to see what would be the best therapy for an individual patient, and we have enough drugs now that it鈥檚 really not an issue. It鈥檚 good in a way, our trainees, our fellows know much less about resistance now than our trainees from five or ten years ago, because we鈥檙e just not seeing it as much. The HIV virus is tricky, so I would never say resistance is not a problem, but it鈥檚 a much, much smaller problem.
Consequences of not taking medicines
Falk: What do you tell a person who says, 鈥淟ook, I鈥檝e been living with HIV for the last X number of years, I鈥檓 feeling fine, I鈥檓 not going to infect anyone else, I鈥檓 living by myself.鈥� What are the consequences of not receiving treatment?鈥�
Eron: We do hear that, because a lot of people don鈥檛 want to take medicines. They don鈥檛 want to be reminded that every day they have HIV infection. What we now know is that not only are there these AIDS consequences that people hear about, AIDS-defining illnesses, but things like kidney disease, which obviously you鈥檙e an expert in鈥攍iver disease, heart disease, are all more likely in patients who have their virus replicating, not suppressed. Turns out there鈥檚 quite a bit of immune activation, their immune systems are revved up, they have a lot of inflammation which affects blood vessels, which affects the kidney, which affects the liver.
So, that patient that you described, that takes a little bit of effort. I have to see that person back and try to talk about these other consequences of having a virus replicating in your body. People can sometimes visualize that, we can measure viral loads and say, 鈥�Look, you have 10,000 copies of the virus in your blood,鈥� and sometimes that helps. I do get that from people, and it does take a little bit of effort sometimes to convince them that if they鈥檙e feeling well, that it鈥檚 better to go on treatment.
Falk: I take care of people with high blood pressure, and you only know you have high blood pressure if you stick your arm in a blood pressure cuff. The reality is you鈥檙e going to take a blood pressure medicine鈥攐r two or three, sometimes鈥攁nd that seems like most people usually do it. Why wouldn鈥檛 you expect that most people would usually being willing to take a single drug? Is there some other issue?
Eron: I think that the vast majority are willing. If you look at our clinic, the goal of therapy now is to get the virus level below what we can measure. That鈥檚 not just because we鈥檙e all just number crazy, but the virus is like a slot machine鈥攖urning, turning, turning. If you can slow that slot machine down, you can end up preventing that virus from becoming resistant. If you can get replication down to zero or close to zero, then you won鈥檛 become resistant to the therapies. If you look at our clinic, between eighty-five and ninety percent of all the patients in the clinic have a viral load that鈥檚 below what we can measure.
Falk: Which is protective for everyone around them.
Eron: Right, and being undetectable means that you are virtually untransmissable. In fact, that鈥檚 what the CDC now says: Undetectable means untransmissable.
How long it takes the drugs to work & how they work
Falk: That鈥檚 just fantastic. How long does it take for these drugs to work?
Eron: That鈥檚 the amazing thing. If you take them, they work incredibly well. If your viral load is 100,000, by four weeks it should be 1,000 or less. It shoots down dramatically fast. I know, for example, if I see a patient and they come back four weeks later and their virus level hasn鈥檛 really changed, either they didn鈥檛 get the medicine, they didn鈥檛 take the medicine, or I gave them the wrong medicine or the wrong instruction. That virus level is a barometer鈥攊t happens very quickly. The immune system recovers more slowly, but the virus suppression happens quickly.
Falk: There are multiple different kinds of HIV drugs. They work differently. Help me understand a little bit how they work.
Eron: The virus essentially has to hijack the machinery of the cell. It鈥檚 like someone coming in to a factory and kind of taking over that factory. The virus has three key steps where it uses its own information. It has to change its genetic material, its blueprint from RNA to DNA, so if you block that, 鈥�reverse transcription,鈥� that鈥檚 one step. It has to integrate, it has to get into the patient鈥檚 DNA, into the chromosome, and that鈥檚 another virus step, so we block that, we block the 鈥�integrase.鈥� Then finally, when the virus has to come out of the cell, it has to take its proteins and construct the capsule, the thing that carries the virus鈥檚 genetic material, the virus blueprint. That鈥檚 done with a protease. Three enzymes: reverse transcriptions, integrase, and protease, those are our main weapons.
Falk: In one pill.
Eron: In one pill. Usually it鈥檚 two of one, and one of the other, and we kind of mix and match, but we鈥檙e actually getting pretty good at this over time.
Falk: Thank goodness. Let鈥檚 say the person鈥檚 viral load is undetectable. What鈥檚 the life span?
Eron: The predictions now are鈥攆or example, someone twenty-five years old, starts on therapy and can stay on therapy鈥攖he predicted life span based on these complicated models is fifty years. Fifty to sixty years, so seventy-five or eighty. It鈥檚 not, it doesn鈥檛 quite reach the normal life expectancy, we think in part because there鈥檚 some intrinsic damage done to the immune system in that period before you get on therapy, so we still have work to do, to get people鈥檚 immune systems back to perfect health. Of course, the longer you鈥檝e waited to get on therapy, the harder it is to get it back, so that鈥檚 a big issue.
Falk: Arguing for early therapy.
Eron: Strongly arguing for early therapy.
Falk: You said you could mix and match. How do you actually figure out what you鈥檙e mixing and matching?
Eron: One of the things I鈥檝e done, and here at 黑料网, we鈥檝e done, is really done those combination comparative trials, we鈥檝e done really scores of them鈥攕ixty, seventy, eighty trials. We were one of the very first sites that did that first cocktail study鈥攜ou鈥檝e seen the pictures in Time magazine, of the handful of pills鈥攚e were one of the first sites to do that cocktail study to show that it took three drugs together, and over the years we鈥檝e done multiple refinements of comparative studies. I鈥檓 really proud of the work that our collective research group, both here and globally, has done to refine the right combinations. There still may be better ones, but literally, when we do a study now, after a year, ninety-two or ninety-three of the patients are suppressed on the medication that we pick, five percent go off the study for all of the reasons that have nothing to do with the treatment鈥攖hey move, they quit the study鈥攁nd one or two percent fail.
Falk: That鈥檚 just remarkable.
Eron: You can鈥檛 do better. We鈥檙e basically trying to refine toxicities and make sure people are on the safest medicine possible.
Commonly asked questions about HIV medicines
Falk: What kind of questions do patients ask you about these medicines?
Eron: Well, they always ask, 鈥淗ow long will I need to take it?鈥� That鈥檚 one of the hardest conversations, because I say, 鈥淲ell, as long as you live, probably.鈥� Now, you鈥檙e going to talk later to Dr. Margolis, who鈥檚 our great hope for curing HIV, and the patients do ask about that: 鈥淲ill there ever be a cure?鈥� They ask about how long they鈥檒l need to take it, they ask about side effects, they ask about things that are common in your life. Can I have to take it with food? Do I have to take it at night? What if I miss by an hour?鈥攖hose are the hyper-compulsive ones. Those are the kind of things that people ask. They鈥檙e worried about taking it for a long time, and they鈥檙e worried about side effects that will impact their life.
Falk: What side effects are there?
Eron: Right now, the ones that patients worry about are really pretty uncommon now. We used to give people medicines they would take every six hours on the clock and set a timer. They鈥檇 have to drink a couple gallons of water, they鈥檇 have nausea, they鈥檇 have diarrhea. Now, the side effects are pretty minor. People do get some stomach upset, but that鈥檚 a minor one. The ones I worry about aren鈥檛 necessarily the things that they feel. Some of our drugs do impact the kidney, so we have to monitor kidney function. One class of our drugs raises cholesterol a bit, so we have to keep our eyes on that. If you had told me twenty-five years ago I would be worried about my patient鈥檚 cholesterol, I would have said, 鈥�You鈥檙e out of your mind!鈥� Now, that鈥檚 what I do now, I worry about cholesterol.
Falk: Happily, and kidney function, which everybody needs to worry about!
Eron: And blood pressure. I worry about all of those things now. It鈥檚 amazing.
Falk: That鈥檚 great. What happens if someone forgets to take their pill?
Eron: Now, that鈥檚 an issue. One of the things that has been so successful in our drug development is we have drugs that have pretty long half-lives, so probably missing a pill here or there, especially once they鈥檝e gotten their virus suppressed, is not as dangerous as it used to be. We used to say that you had to be ninety-percent adherent to be successful, but I can promise you, our clinic, with ninety percent of people suppressed, ninety percent of our two thousand patients are not taking their pills every single day, because they鈥檙e all human like me and you, and we miss now and then.
Falk: Missing for an hour or two鈥�
Eron: Not a problem. The issues are, people who either lose access to their therapy, or somehow become either compromised because of life situations like depression, substance use, insurance鈥�
Falk: Something happens.
Eron: It鈥檚 those big gaps in therapy that matter, where they stop for a week or a month, and as the drug level goes down, that wheel starts spinning. Once it starts replicating, you get mutations, and some of those mutations lead to resistance.
Falk: That鈥檚 of course what one is trying to avoid at all cost. What do you do if somebody does get resistant disease?
Eron: If it turns out that someone鈥檚 been on therapy, and their virus level comes up, first we get a resistance test. We have a lot of information about what drugs work against these specific resistant viruses, so that the problem there is that therapies get more complicated. There aren鈥檛 as many single tablets that you can give to someone who is resistant to a couple of those classes that I talked about鈥攔everse transcriptase, integrase, protease, so then the therapy gets a little more complicated. It鈥檚 a little harder to take, so you鈥檙e in that space where someone had trouble taking a simple therapy, and then you鈥檝e got to give them a more complicated therapy. Then they need more support鈥攖hey need phone support. We have a really strong social work and pharmacy staff that will call people, help them with refills, but that鈥檚 when it gets tricky.
Falk: In reality though, the message has got to be, start early, take it every day, and just don鈥檛 think about it.
Eron: What I tell people, if they鈥檙e a woman and they鈥檙e child bearing, 鈥淒o you want to have kids? It鈥檚 okay.鈥� If they already have kids, I say, 鈥�Save for college鈥攈ave that child go farther as you want them.鈥� If they鈥檙e a little older, I say, 鈥淪ave for retirement鈥攜ou can live a normal life.鈥� That鈥檚 what I try to tell them as best as I can.
Current research in HIV treatment
Falk: Right. Let me ask an obvious question: You鈥檝e made tremendous progress and we鈥檙e all hoping that there will be a cure, but on the near horizon, is there going to be every-other-day therapy, or is there going to be an opportunity to stop?
Eron: Super question. There are a couple of things we鈥檙e doing. There鈥檚 a move now to develop longer-acting therapies鈥攊njectable therapies. In fact, we have a study going now where you can get an injection of two drugs and we鈥檝e learned that if you鈥檙e suppressed, two drugs work, and the study is comparing monthly injections with every-other-month injections.
Falk: Wow.
Eron: Now, the intramuscular injections are a little bit tough, but it鈥檚 moving in that direction. There鈥檚 another new drug that鈥檚 recently been discovered that is incredibly potent, which means you can give very small amounts of it. It鈥檚 possible that this drug could be put in one of those devices that they use for pregnancy prevention, for contraception, one of those long-acting Implanon or Nexplanon devices, so we really are thinking about how we might be able to give people therapy on a quarterly basis or even a six month basis.
Falk: That would be amazing.
Eron: Sort of like what was done in osteoporosis鈥攕tarted out as a pill, was a monthly, and some people get once a year infusions for their osteoporosis, so it鈥檚 possible. That鈥檚 kind of the new frontier that we鈥檙e really working on.
Changes in HIV outlook over the last twenty-five years
Falk: Help me reflect for a moment. Now you鈥檙e describing a medicine that you regularly could take once a day, you鈥檙e describing in the near term that there may be drugs that you could use every other month or perhaps quarterly鈥攔ecycle back twenty, twenty-five years ago. What was it like then?
Eron: This is something that I鈥檒l never forget. When I first came here to 黑料网 in 1992, we literally had people die every week. There was another person who we knew and took care of who died that week and we really were kind of caretakers and helping people through the last stages of a fatal illness. It鈥檚 just been totally transformed. Now, it鈥檚 rare that one of my patients dies. Sometimes they do. I recently had a patient die almost of old age鈥攖hey had cancer, but they were in their late seventies, almost eighty years old, their family was around them, and they died from something other than HIV. It was just incredibly different. That鈥檚 what I鈥檓 hoping for all of my patients.
Falk: Die with your HIV, but not from your HIV.
Eron: Exactly.
Falk: That鈥檚 a wonderful thought.
Eron: It is.
Falk: Thank you, Dr. Eron, for a really informative discussion.
Eron: This was really fun, thanks for inviting me.
Falk: Thanks so much to our listeners for tuning in. In our next episode, we鈥檒l be joined by Dr. David Wohl, for a discussion on managing your health and aging with HIV. If you enjoy this series, you can or . Thanks so much.
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