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Michael S. Saag, MD: Hello. I'm Dr Michael Saag, professor of medicine and infectious diseases at the University of Alabama at Birmingham. Welcome to season two of Medscape's InDiscussion series on HIV. Today we'll discuss primary care in HIV, with a special focus on vaccines. First, let me introduce my guest, Dr David Spach, professor of medicine in the Division of Infectious Diseases at the University of Washington in Seattle. Welcome to InDiscussion.
David H. Spach, MD: Good morning.
Saag: It's good to be with you. When did you first get involved with HIV care, and how did you develop the special focus on primary care within an HIV clinic?
Spach: I've been involved in a Ryan White clinic in Seattle at Harborview Medical Center, which is part of University of Washington, for more than 25 years. I came into the HIV epidemic as a care provider around the time you did. Just through the experience of having so many trainees in the clinic and so many residents in the clinic who are actually doing primary care for people with HIV, I've naturally evolved with more of an interest in primary care out of necessity, as patients diagnosed with HIV are living longer and are developing more and more primary care problems. This is just a natural evolution over time.
Saag: I think it's happening with all of us because, fortunately, the medications to treat the virus are so good now that people are going to live a relatively normal lifespan and not have any difficulties with HIV. In my practice, I found that with 85% of the patients I see, maybe 90%, we're not talking about HIV at all.
Spach: I share the same sentiment. This specialty has really changed compared with 20 years ago, when the focus was primarily on stomping out one opportunistic infection after another, to now, where we're really dealing with people who are very stable and who have a plethora of primary care issues. We're really dealing with an aging population; we're going to continually be dealing with more and more problems as people age that are really primary care issues.
Saag: As we have all focused on primary care treatment of patients diagnosed with HIV, we have focused a little bit more on vaccinations. I am talking about routine vaccinations. One of the vaccines that has been really topsy-turvy, at least for me, is the pneumococcal vaccine. There's a whole bunch of them, like a pneumococcal polysaccharide (PPS), or a pneumococcal polysaccharide vaccine (PPSV), or pneumococcal conjugate vaccine (PCV) 20, -15, -23. It sounds like we're calling a football play. Can you straighten me out in terms of what these vaccines are and how we're supposed to use them?
Spach: So many times in our care of patients, things get more and more complicated over time. As I'm going to outline with this pneumococcal vaccine story, we actually have a great story this year where we finally got something really simple for all clinicians who are trying to immunize people with HIV against pneumococcal disease. People with HIV clearly have an increased risk for severe pneumococcal disease, pneumococcal bacteremia — in particular, pneumococcal pneumonia. This is a high priority to try to immunize people who have HIV. Years ago, we only had this polysaccharide vaccine, which is essentially just taking a piece of the pneumococcus and using it as a vaccine. Then there was the very first conjugate vaccine called conjugate pneumococcal vaccine 7, and it was a huge success when it was introduced because it basically takes this pneumococcal antigen, attaches it to a protein, and you get a much better immune response. This has been widely used in kids. It's been a tremendous success everywhere where it's been used. As the pneumococcus has seen this, it has evolved; it has developed new strains that tend to move to the heap at the top. They've evolved this vaccine to now be a pneumococcal vaccine 13, or PCV13. Further adjustments have recently occurred where we now have what you're referring to, which is the PCV or pneumococcal conjugate vaccine 15, and PCV20, which is pneumococcal conjugate vaccine 20. The old pneumococcal vaccine, the very first one to come in, we call PPSV23, and that's just a polysaccharide vaccine that is not conjugated and does not give as good an immune response.
Saag: What is the order in which we give these if somebody comes in who has never had the vaccine before?
Spach: This used to be really complicated. It used to take 5 minutes to explain this to one of our trainees in the clinic. Now it's great. You can have a person walk in and do one-and-done, meaning, you can give them the pneumococcal conjugate vaccine 20 and you're done. The other option now that is very acceptable is one-and-one, which is the pneumococcal conjugate 15 plus the polysaccharide vaccine at least 8 weeks later. I won't even get into it because it was such a complicated structure we had in the past. But I really think this is going to dramatically improve the success just because of the practicality of this.
Saag: I think we would have probably spent at least half this podcast talking about the prior convoluted approach. To summarize, the PCV means conjugated and the PPS is the polysaccharide. I think that's the way we can keep it straight. Let's move on to another vaccine that we really need to think about a lot, and that's the hepatitis B vaccine. We know that our patients are at higher risk for hepatitis B anyway. First, we have to check and see if the patient has already been infected. If you have a new patient, you want to run a hepatitis B panel. Take me through that and what you're looking for before you decide whether you're going to give any hepatitis B vaccine.
Spach: I'm glad you asked this because years ago, there was a lot of debate about what we should be doing for screening people with hepatitis B. Now the CDC recommendations have come out, and in the opportunistic infection guidelines, the recommendations have been really clear. We want the triple screen. What the triple screen consists of is the hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis B core antibody. Those three things together give you all the information you need. This old practice of looking at e antigen, e antibody, that is no longer recommended. You should really just think of it as a triple screen for everybody. I should mention that for all of you that are in primary care, you're soon going to see widespread recommendations for universal hepatitis B screening and immunization in the general population, in the adult population. In the past, we were a little bit unique in HIV in screening everybody. But you're going to see that this is a much more widespread recommendation applicable to primary care. The same thing is going to hold in primary care: Screen with the triple tests that I just recommended.
Saag: Let's take a scenario. If somebody has a positive surface antibody but a negative core antibody, and a negative surface antigen, that means they've already had a vaccine. Do we want to check levels or do we just accept that they're immune and move forward?
Spach: If they are clearly positive on the antibody test — most of the commercial assays use a threshold of at least 10; these are international units. If a person pops up as surface antibody positive, core negative, antigen negative, then we consider those individuals good to go and immune. You make a great point that that really does indicate that they've seen the vaccine before because the hepatitis B vaccines are made of surface antigen — pure surface antigen. When somebody's seen the vaccine, they only respond with the surface antibody positive; they don't develop a core antibody. If you see the core antibody, they've seen the virus.
Saag: Exactly. If there is a core antibody, even with a negative surface antigen, that person has been infected previously with actual hepatitis B virus. A lot of our patients, if they have been infected previously, are surface antigen positive. In that setting, just to complete that thought, we want to make sure in almost every case that they are on a tenofovir-based regimen, right?
Spach: Absolutely. In HIV now, the recommendations have been really solidified to say that we like to have two anti–hepatitis B agents on board. Using our typical backbone of tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) or tenofovir alafenamide/emtricitabine (TAF/FTC), we really have our bases covered just kind of naturally. You don't want to forget this, because you may see somebody who wants to switch to a simplified two-drug regimen, or with the enthusiasm of switching to these two-drug injectable regimens like cabotegravir/rilpivirine. In that case, you're not going to have hepatitis B coverage on board. I'm glad you're bringing this up because clinicians need to mark it. If patients have been surface antigen positive, you don't want to forget that and you want to make sure that you're keeping this in mind with any further regimens. If you get a surface antigen, I think you really want to follow that with the hepatitis B DNA test as well.
Saag: Exactly. Just so we're thorough here, a lot of times we're de-escalating the antiretroviral regimen to dolutegravir with lamivudine (3TC), but in the setting of somebody who is surface antigen positive, we don't want to do that because we can get resistance to the 3TC, the lamivudine, within just a couple of weeks, right?
Spach: Absolutely. The tenofovir-based and entecavir regimens are much more effective against hepatitis B than are lamivudine or emtricitabine, which really have a very low threshold for the virus marching through it. Again, I think two agents that are active against hepatitis B is what's recommended for people with HIV.
Saag: I'm going to put us in reverse a little bit. Go back to that screening scenario: somebody who is hepatitis B surface antigen positive already, and let's say they don't have surface antibody — do you vaccinate them?
Spach: No. I think if they're surface antigen positive, the priority is really just the treatment, and there's no benefit of immunizing those individuals.
Saag: Okay. Now we're going to focus on a new patient who comes in negative for all three: negative antibody, negative antigen, and negative core antibody. That means they are really great candidates for hepatitis B vaccination. What do you use?
Spach: That's a typical scenario. It comes up all the time in the clinic, and the idea there is that they've never seen the virus and probably never saw the vaccine. It is possible that they may have seen the vaccine as a child and they've already developed a loss of immunity. I think in this case, we need to consider that we're starting off from ground zero. These individuals we're typically going to immunize with the old hepatitis B single-antigen vaccines. Those require three shots over a 6-month period. It's a little bit cumbersome. The responses are not great. What's very important for everybody to know is the new recommendation and the opportunistic infection guidelines, which are that if you're using the old traditional single-antigen hepatitis B vaccines, those individuals should get a double dose with each dose, sort of like what we've done over time with dialysis patients. This is a new recommendation. Patients are supposed to get three doses, double dose. The other new recommendation, as many of you are familiar with: the newer hepatitis B vaccine that has a CpG adjuvant, and that vaccine has a very potent immune response and only requires two doses a month apart. It is a much more practical dosing strategy. It's a little more expensive. There aren't a lot of data in HIV, but they're coming. I think there's now an official alternative. It's not as high of a recommendation as the old traditional three-dose single-antigen vaccine. But there's now this new recommendation. Not to confuse everybody, but the last thing to mention in the field of hepatitis B is that there is a brand-new three-antigen, or triple-antigen, hepatitis B vaccine that just made it onto the Advisory Committee on Immunization Practices (ACIP) recommendations this year. We're not using that yet in the field of HIV.
Saag: So the two-antigen injection — I know we're not supposed to use trade names, but we kind of almost have to here to keep us straight — but that's Heplisav. Is that how you pronounce it?
Spach: Correct. That would be Heplisav-B. Also, just to clarify for providers, because I think vaccines are the place where it's almost impossible to separate these out: The old traditional antigen vaccines are going to be like your Recombivax or your Engerix-B; the new vaccine that we're talking about, with two doses, is the Heplisav-B, and that's the one that has the very potent adjuvant and the better immune response that only requires two doses. The new triple antigen is called PreHevbrio, and many of you may not have even heard about it because it's fairly new and it hasn't made it into the mainstream. But many people are getting this triple antigen PreHevbrio confused with Heplisav-B. They're distinct vaccines, and in HIV right now, of those, only Heplisav-B is recommended as an alternative option for people starting off getting vaccinated.
Saag: We don't use a double dose of that.
Spach: Correct. Standard dosing with the Heplisav-B.
Saag: I think that's really clear, David, and I think it's kind of up to us whether we use that Heplisav as only two doses or as the double-dosed original vaccine given three doses a month apart and then 6 months later. Let's talk about hepatitis A vaccination. A lot of times there's a combo, right? You can give a hepatitis B vaccine and a hepatitis A vaccine at the same time. For men who have sex with men (MSM), they're at higher risk for hepatitis A. What's your recommendation there?
Spach: I'm really glad you asked this question because I think this raises a point that may not have been thought about at the time these vaccine recommendations came out. In the HIV world, it is now recommended to use a double dose of the hepatitis B vaccine. However, if you were using the combined vaccine (the trade name is Twinrix), which is hepatitis A and hepatitis B, it only includes the single dose in there. In the past, that was, I think, a very reasonable recommendation. But now I don't see the value of using that because if you're going to use it, you then have to add on and use a second hepatitis B vaccine on top of it. That's a minor distinction. I carefully looked at this, and the dose in the Heplisav-B is only single-strength hepatitis B antigen. It creates a little bit of a dilemma that we didn't have in the past.
Saag: We could use a single hepatitis A vaccine by itself if we wanted to do that.
Spach: That's what I'm doing now. Exactly.
Saag: That's what I'm doing as well. I wanted to make sure we covered that. This has become the substitute for complexity that we used to have with pneumococcus, but I think it'll probably straighten out in the next couple of years. For now, I think you've made it very clear what we should be doing. Let's move on to varicella-zoster vaccines. Using trade names, this is Shingrix. Tell me how you assess the patients that are especially new to your clinic, but maybe even some of your established patients who haven't been vaccinated for varicella-zoster virus (VZV). Tell us what your approach is for using these vaccines.
Spach: For people who haven't done a lot of HIV care, especially over a longitudinal period of time, shingles is very common and it can be really devastating. You may have been fortunate in seeing people with very mild episodes of shingles, but unfortunately I have seen some severe cases of shingles. I'm sure you've seen a number of severe cases. We tend to see more severe cases in people with HIV, especially with more advanced immunosuppression. I'm a big proponent of trying to immunize people against VZV. As a reminder, this is the chickenpox virus that's in somebody's body. It's going to be reactivating. Essentially by giving this vaccine, you're trying to boost their immune system, keep it in the cage and prevent it from coming back out in the nerves and causing clinical shingles. Here's what's new: We used to recommend giving this to people age 60 or older; then the recommendations changed, saying we could give the zoster vaccine to people age 50 or older. The newest recommendations now: All adults with HIV should be recommended to receive this new zoster vaccine called Shingrix. The good news is that the newer Shingrix vaccine does not have any live virus in it, so you cannot cause a clinical varicella infection or disseminated viral infection in people. It's a very safe vaccine that requires two doses, typically 2-6 months apart. It is very effective. It is much more effective than the older Zostavax, which was a live vaccine that we gave to people with HIV only if their CD4 count was above 200. This new vaccine is much better and safer, and it's great that we're now seeing this as a widespread recommendation to use in people 18 or older. To answer the question, we really try to get everybody who's an adult the shingles vaccine. It wouldn't be the very first thing I would do, but we really do view this as a high priority, and it's great to see this new recommendation.
Saag: Some of the complexity is that we've lived through a life span here where those of us who are over the age of 40 or 50, we probably had chickenpox as a child and we're harboring the virus, and we're preventing that reactivation. For people born after 1990 or 1995, they were getting access to some form of a VZV vaccination and may not have had primary chickenpox. What you're saying is, regardless of whether they've had prior vaccination, a younger person or not, we should go ahead and give the Shingrix vaccination automatically, even without knowing what their prior history is.
Spach: Absolutely. It really got simplified. Since you can't cause a disseminated infection with somebody, it's a safe vaccine to give. Just to remind everybody, though, the varicella vaccine that is given to children, the chickenpox vaccine, is a live vaccine. To distinguish, the new shingles vaccine is not a live vaccine and it's to prevent shingles. The last thing I would say is that even though it's a very safe and very effective vaccine, I do respect some of the side effects that people get with it. It is a lot like a COVID vaccine, where not everybody gets side effects, but for some people it really knocks them down and puts them in bed for about a day. I now counsel everybody who's going to get this new Shingrix vaccine that it works and it's safe, but be prepared that for maybe a day you may feel pretty bad. I do let people know that in advance now.
Saag: You mentioned live vaccines. Let's list those here and talk briefly about when not to use those vaccines.
Spach: I think there are a couple of key live vaccines. There is a live nasal influenza vaccine that should not be given to anybody in HIV, regardless of CD4 count. We make some distinctions based on CD4 count for some common vaccines, where anybody with a CD4 count less than 200 or with a percentage of CD4 less than 15, we don't want them getting the MMR vaccine and we don't want them getting the varicella vaccine that I just mentioned a minute ago. Let's say that you were screening an adult. Maybe they had never gotten childhood vaccines. You say we're going to screen them for varicella and give them that. You should not give that vaccine to someone with a CD4 count less than 200 or a percentage less than 15. Now, there are a few other ones that we don't really deal with a lot in the clinic that I'll just briefly touch on. If somebody's traveling or they're in another country, we don't want to give them bacille Calmette-Guérin (BCG). We don't want to give them the live typhoid 21aA. And we don't want them to get smallpox vaccine, which is different from the monkeypox (mpox) vaccine called JYNNEOS. Those three vaccines are also on our do-not-give-at-any-cost list — BCG, live typhoid, smallpox — but the big ones for you to remember are the live influenza, MMR, and varicella vaccines.
Saag: Perfect. Let's move to COVID. Do you treat your HIV patients in regard to COVID vaccination any differently than we would a patient who doesn't have HIV?
Spach: I'd love to hear what your thoughts are on this, because I know you have really been involved with a lot of different avenues in COVID. In our clinic in general, our practice has been to approach this very similarly to the general population. Our biggest issue, like in the general population, is getting them the vaccine, period. I think we know that people with lower CD4 counts probably don't respond as well. A number of national experts have raised this point, so I'm definitely more hypervigilant about them getting booster shots, especially if their CD4 count was low. But in general, we use the same dosing strategy, the same dose of the vaccine, the same vaccines, and we really try to get them one of the two main vaccines, the mRNA vaccines. I'd love to hear what you think, Mike.
Saag: I agree. I treat all my patients exactly the same as I would someone who doesn't have HIV and just follow the CDC guidance. Up until just a couple of months ago, we would start with a primary series and then follow with a booster. Now, I think the recommendations are leaning toward using the bivalent up front because Omicron is the variant that's out there. You mentioned the JYNNEOS vaccine for monkeypox, or mpox, as we call it now. You're using it for your MSM at risk, I assume. Is there any trick or hint that you would want to give us about using that?
Spach: Yes. I'm sure in Birmingham, your STI clinics and your HIV clinics really saw the impact of a major mpox outbreak and epidemic in the US in 2022. Vaccination has been incredibly helpful and impactful to minimize the number of clinical infections. Absolutely, as you said, we're going to want to try to immunize people who really are primary risk, which is predominantly MSM. There are a couple of things to mention with the mpox vaccine. Number one, patients can use this vaccine as postexposure prophylaxis. Ideally, you're trying to do this within 4 days. You can use it out to day 14. Just remember, using this vaccine any time after day 4 and up to day 14 is sort of plus-minus how well that's going to work. The primary way we're using the mpox vaccine is as a preventive vaccine for people who have not been exposed. There are two doses of this given at least a month apart. You can give the vaccine up to 4 days early, but you shouldn't give it 10 days early. If you give the vaccine 10 days early, you start over. Ideally, you give the vaccine a month after that. You can stretch that out to be an extra 7 days, ideally. If someone's late in getting their vaccine, just keep going where you are. As an example, if somebody is supposed to get their second dose of mpox vaccine and they're a month late, just give it to them and you're done at that point. There was a lot of vaccine shortage. It became clear from recommendations of the CDC that you could use intradermal dosing as opposed to subcutaneous (sub-Q), which is how we started using it. The intradermal dose is one fifth the sub-Q. Essentially, you made the vaccine be five times more in terms of stock, in terms of what you had if you go the intradermal route. That's what our clinic pivoted to in the fall when that recommendation came out.
Saag: Perfect. Well, our time has flown by, chock full of information. This has been a wonderful podcast for all of us and one perhaps that folks are going to want to listen to again because it has so much good information in it. We've just finished a conversation with Dr David Spach about vaccines. We went over the pneumococcal vaccine and the difference between the conjugate and polysaccharide vaccines. We talked about hepatitis B and all the nuances. We talked about VZV vaccine and how that has become kind of simplified. Then we wrapped up with discussions of COVID and mpox. I don't think we could get a whole lot more into a 25-minute period. Thank you, Dr Spach, for being with us. It's been fabulous. Thanks to all of you for tuning in. If you haven't done so already, please take a moment to download the Medscape app to listen and subscribe to this podcast series on HIV. This is Dr Michael Saag for InDiscussion.
Listen to additional seasons of this podcast.
Resources
HRSA Ryan White HIV/AIDS Program
Pneumococcal 7-Valent Conjugate Vaccine
Immunizations for Preventable Diseases in Adults and Adolescents Living With HIV
Drug Database: Hepatitis B Vaccine
Interpretation of Hepatitis B Laboratory Results
Screening and Testing for Hepatitis B Virus infection: CDC Recommendations — United States, 2023
Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV
Heplisav-B® (HepB-CpG) Vaccine
PreHevbrio: A New 3-Antigen Hepatitis B Vaccine for Adults
Hepatitis A Vaccine Inactivated (Rx)
Zoster Vaccine Recombinant (Rx)
Live Attenuated Influenza Vaccine [LAIV] (The Nasal Spray Flu Vaccine)
Typhoid Fever and Paratyphoid Fever Vaccination
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Cite this: HIV and Primary Care: What Are the Dos and Don'ts of Administering Vaccines to People With HIV? - Medscape - Jul 13, 2023.
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