ACUTE HIV INFECTION Rona Vail, MD Lead HIV Clinician Callen-Lorde Community Health Center

Clinical Education Initiative [email protected]

5/15/2019

Acute HIV Infection [video transcript]

(00:00):

Good afternoon everyone. Thank you for joining 'This Month in HIV' today, Wednesday, May 15th. I'm not sure where all of you are, but the rest of us are kind of happy we'll finally see some sunshine today here in New York City. I hope the rest of you have gotten out of the rain and now are enjoying it as well. So today's topic is being brought to us by Dr. Rona Vail with Callen-Lorde Community Health Center on Acute HIV Infection and a couple of notes for today's session right now, everyone will remain muted. Please note, there is a chat box function. If you could please find that and if you have any questions for Dr. Vail, please put them into the chat box. We will review them with her when we end the presentation until then, please make sure to do that. Remember next month will be our 'This Month in HIV' which will be Care Considerations For the Older Patient. That information will be sent out later for the June 'This Month in HIV.' Of course, this is presented on behalf of Mount Sinai Institute for Advanced Medicine and the New York State Department of Health AIDS Institute Clinical Education Initiative grant, or CEI. So we thank them for that. And for now I'll just move right into it. Dr. Vail is an HIV specialist providing medical care to HIV infected individuals for over 30 years. She has been at the Callen-Lorde Community Health Center for the past 20 years. In addition to patient care, she has provided education training on HIV to the community members, students, residents, and medical professionals. She also serves on the New York State Department of Health AIDS Institute Medical Care Criteria Guidelines Committee, as well as the Quality Care Committee. So with that, I'm going to turn it over to Dr. Vail.

(02:09):

Good afternoon, everybody. So I'm going to be talking about Acute HIV Infection. I have no conflicts. So I'm going to be discussing transmission dynamics and pathogenesis, as well as how to recognize the signs and symptoms and diagnostic algorithms for a diagnosis.

(02:28):

Let's start this off with a case. RB is a 38 year old man who presents with fever, body aches, headache, and a rash. Five days earlier, he was evaluated in the emergency room with the same symptoms. In the emergency room, the discharge summary shows that labs included a negative HIV test, a negative syphilis test, and an LP with findings consistent with viral meningitis. He was sent home to rest and take anti-inflammatories and anti-fever medication. When he comes to see you, a chart review shows that he had HIV tests one year ago and three months ago, which were HIV negative. At his last HIV testing, the patient reported three instances of condomless sex in the past six months. Two are associated with alcohol use and one was associated with the use of crystal methamphetamine. He declined PrEP at that visit. So we did a fourth generation, another fourth generation rapid test in the clinic, and that test was now positive. Confirmatory tests then showed the fourth generation lab based test was also positive. The HIV antibody test was negative, but the viral load came back at 3 million copies. So RB was diagnosed with acute HIV infection.

(03:46):

Acute HIV infection is the earliest stage of HIV infection when you have the presence of virus and then a few days later p24 antigen, but you do not have antibody levels yet. Virus is peaking in the blood and genital fluid. Early HIV infection is the first six months of HIV infection.

(04:24):

So to make the diagnosis of acute HIV infection, you have to have HIV in the differential diagnosis. To their credit in the emergency room, they seem to be thinking about HIV because they did do an HIV test. However, they didn't do the correct HIV test. An antibody test, even a fourth generation antibody test, is going to be negative in the earliest stages of acute HIV infection. By the time he came to us, several days later, that rapid test was now positive, but in the ER what they needed to do was a viral load.

(04:57):

Why does it matter that we recognize acute HIV infection? Well it really matters from a public health point of view, as well as to the person themselves. From a public health point of view, a high viral load oftentimes in the millions during acute infection means high transmissibility. Acute HIV infection and when you have somebody who has acute HIV infection, you have somebody who is sexually active or drug injecting, who at least recently didn't use a condom or wasn't using clean needles, and they don't know they're HIV positive. If we can diagnose them in that moment, we can potentially halt forward transmissions to new partners. Identification also means we can go backwards and do contact tracing of recent contacts to test them and warn them about the potential HIV exposure. There is also potential benefit to the infected person of treating very early, and we'll cover that a little bit later.

(05:53):

So how transmissible is it? Wawer called it brief but efficient. In serodiscordant partners the highest rates of acquisition were during early infection. Primary and early infection is estimated to be nine times more infectious than chronic infection.

(06:14):

It's actually estimated that 29 to 50% of all new HIV transmissions are being transmitted by people who are in early and acute HIV infection. So clearly finding these folks is super important for driving down rates of HIV in the community.

(06:31):

So if people get an HIV diagnosis, does that change their behavior? Well, the answer is oftentimes yes. In this study, there was a significant drop in the number of sexual partners after diagnosis. After diagnosis more than 95% of sex acts were now with people who were also HIV positive, what we call sero-sorting or choosing to have sex with somebody who is the same status as you are. There was no significant change in the number of sex acts, but a significant increase in the use of condoms. So behavior change

often, but not always does happen on diagnosis. And if behavior change doesn't happen, treating folks and getting their virus down will also help.

(07:13):

So what's happening during acute HIV infection. Let's look at the stages. At day zero, you have HIV present at the mucosal surface during sexual transmissions. Over the course of the next two days, virus is being collected by dendritic cells and it's carrying them into the lymph nodes. For us to prevent HIV infection with post-exposure prophylaxis, we've got to get it before the virus is entering into the lymph nodes and then replicating in CD4 cells. Post-exposure prophylaxis, 72 hours or less. HIV is replicating within the CD4 cells, goes out to the blood and then goes out to other organs very quickly. So at this point, you're getting a positive viral load.

(08:00):

Let's take a look at the sequence of the appearance of laboratory biomarkers for HIV infection. After exposure to HIV, the first thing that's going to appear is HIV virus, HIV viral load. HIV RNA starts to rise 10 to 11 days after exposure and peaks and rises very, very rapidly. A few days later, you get p24 antigen. p24 antigen is a viral core protein that transiently appears in the blood during this first couple of months of new HIV infection. It then disappears, but it will actually make an appearance in very late stage AIDS. But in between, we don't see p24 antigen. And then comes HIV antibody. The fourth generation test was such a big breakthrough because the fourth generation test not only test antibody, but it also tests p24 antigen. So therefore, it is a much better test than our older HIV tests.

(09:07):

Whenever we're ordering an HIV test, to diagnose HIV infection, we need to be aware of the window periods for testing. The window period is the time between when a person is first infected with the virus, and when the test will turn positive. You can see the various window periods for the different generations of HIV tests. With our earliest HIV tests, people had to wait two, three months or longer before they we knew if they were HIV positive after an exposure. The third generation test really was a big breakthrough because the third generation test included a IgM antibody, as well as IgG antibody. And then again, the bigger breakthrough of the fourth generation HIV test. But when we're ordering a test, we want to know whether that test is likely to be positive based on the time from exposure.

(10:00):

So if we compare the window periods for different tests, what we see is if we take a look first at the viral load. So the top here is the viral load. At day eight after exposure, 25% of people will already be reactive by then. 50% will be reactive by day 12, but there are some people who will not turn positive until 33 days later. You have to go out 33 days before you can be 99% sure that a negative viral load is truly negative, Otherwise the person could still be in the window period for HIV infection. The fourth generation blood based lab based test, the antigen/antibody lab based test, turns positive first about five days later. But then again, can be as long as 42 days to turn positive for some individuals. So 75% of people will be positive by three weeks.

(10:51):

The rapid lab test, the rapid tests in clinic, the fourth generation takes a little longer than the lab based fourth generation test. And the third generation IgM tests take a little longer than the fourth generation tests. Here we have our confirmatory antibody tests. So once somebody has a positive test, either viral load or fourth generation, we have to now do a confirmatory test to make sure it's a true positive. The confirmatory tests first turned positive usually after a month after infection or longer. So it takes a while for some of these confirmatory tests to turn positive.

(11:28):

How good is the fourth generation test at finding acute HIV? This was an interesting series of studies that took people who were fourth generation viral load positive, but third generation HIV antibody test negative. They then ran a fourth generation test to see if the fourth generation test would have captured the tests that the third generation missed. What you can see is that the fourth generation test detected acute HIV in over 75% of the time. So the fourth generation test is a great test, really narrows the window period from exposure to positive test, which is why the fourth generation antigen/antibody test is our test of choice. And it's what is recommended by the CDC for routine HIV testing.

(12:18):

Now, this is an algorithm for routine testing not for when you suspect acute HIV, but let's go over this algorithm first. So the first step is you're going to do a fourth generation test. If that test is negative, it tells you you're negative for HIV antibodies and you're negative for p24 antigen. It's important to remember they still be in the window period for early infection, but we know that they're negative for antigen and antibodies. If they're positive, then the next confirmation test is an HIV-1/HIV-2 antibody differentiation test, many labs do this as a reflex. If you get a positive fourth gen viral load in a lab, it reflexes to this differentiation test. And that test tells you if you're HIV-1, HIV-2, both, or neither or indeterminate. If the fourth generation test is positive and this test is negative, then you have to do a viral load. The viral load, if it's positive, diagnosis acute HIV infection, because you have a positive viral load, a positive fourth generation test, but a negative antibody test. If this test is negative and these tests are negative, then you're negative for HIV and that fourth generation test was a false positive test.

(13:38):

This is an algorithm for testing for acute HIV infection. So again, this is persons with signs or symptoms of acute HIV infection or somebody who had a high risk exposure in the last four weeks. In this case, you have to do a viral load plus and antigen/antibody screening test. If both of those tests are negative, there's no evidence of HIV. If the viral load is positive and the antigen/antibody test is positive, you have a confirmed HIV. If the viral load is over 5,000 but the fourth generation test is still negative, you have a presumptive diagnosis of HIV and you go ahead and start treatment, and you can repeat testing later to just to look for the HIV-1 or -2 antibodies. If the viral load is less than 5,000, now we're in a tricky spot because this could be a false positive test. Less than 5,000 could be a false positive viral load. So in this case, we retest HIV. If HIV is not detected, it was a false positive. If it's detected again, we have a presumptive diagnosis.

(14:45):

So the diagnosis of acute HIV is really centered both on getting an early fourth generation test, but also recognition of symptoms of acute HIV. Unfortunately, we medical providers are not very good at detecting acute HIV infection. In this study of 46 patients who presented with symptoms of acute HIV infection to either a medical provider or an emergency room, 41 to 46 patients developed an acute syndrome. Of those patients who developed acute symptoms, primary HIV was only diagnosed at the first visit 26% of the times. All the other folks needed two, three or more visits in medical care systems to have their HIV diagnosed. So we definitely need an increased awareness by primary care providers and emergency room providers of the symptoms of acute HIV.

(15:45):

So which of the following symptoms is typically not present in persons experiencing acute HIV? The answer is cough. Generalized lymphadenopathy is common, rash is common, fever and oral ulcerations can happen. But cough would be uncommon.

(16:07):

In this big meta analysis of different reports of acute HIV infection, that was in AIDS 2002, what you can see is the most common symptoms are fever, fatigue, malaise, joint pain, headache, loss of appetite, basically symptoms of acute viral syndromes. Pretty nonspecific, which is oftentimes why it's missed. Rash while present is only present in these series 51% of the time. So while rash may be present, it may be missed. It may not be there. The other thing I'll point out is the ulcerations, oral ulcers, sores on the anus, and sores of the genitals are not that common, but if you have somebody with a febrile illness and ulcerations, HIV should jump to a very high position in your differential diagnosis. Think HIV when you see fever and sores.

(17:06):

I just want to review with you quickly a really interesting study from Thailand and East Africa, with a group of folks who are looking to really delineate what the signs and symptoms of acute HIV were and the timeframe to develop them. And so what happens in retrospective studies, we're going backwards and asking people what their symptoms were, but this was actually a prospective study. They took over 2000 negative high-risk for sexual transmission folks followed them over six years and they actually did qualitative viral loads two times a week during that whole time period. And by doing this, they did find 50 seroconversions. For the people who seroconverted, they had two visits a week for nine visits over the course of the first month of seroconversion to really delineate the symptoms and immune markers. And they found some interesting things.

(18:01):

So on this axis, we see the number of reported symptoms. And on this, we see time after infection. And what we can see is that 88% reported at least one symptom, but that means 12% reported no symptoms at all even when they're being followed really, really closely. Of those 88% that reported at least one

symptom though, 71% of acute medical visits there were no symptoms. So a lot of people have low to no symptoms. You can see the mean and median number of symptoms at the peak point was only one to two. And symptoms occurred the most just before peak viral load. And you can see that some people were very, very sick with multiple symptoms, but a lot of people had little or no symptomatology. So a lot of these folks were never going to be able to find, because they're not presenting with all the things we think of as associated with acute HIV syndrome. But for those patients who do present in this range, we want to be able to find them and diagnose them.

(19:07):

So, which would you include in the differential diagnosis of acute retroviral syndrome? Influenza, Epstein-Barr mononucleosis, cytomegalovirus, secondary syphilis, Rocky Mountain Spotted Fever, streptococcus, viral hepatitis. Well, all of the above is the answer. All of these can have the similar symptoms to acute HIV. Again, one of the reasons that you have to have HIV as a suspicion, because there's a lot of other things one might be diagnosing here other than HIV.

(19:45):

So the rash of acute HIV is a very typical viral exanthem. However, sometimes that viral exanthem is very, very sort of mild. And you can see how it could be very, very easy to miss somebody who's presenting with fever. Even if you look at them, you might not think rash. You might just think, 'oh they have a couple of pimples on their chest' and not think that this is actually a viral exanthem. Oral lesions are common in acute HIV infection. These are some of the oral ulcerations of acute HIV infection as well. Linear gingival erythema can be a finding of acute HIV infection And genital ulcer disease can be seen in acute HIV infection.

(20:49):

So, which of the following lab tests is typically normal in persons with acute HIV infection? Metabolic panel. All the other tests can be abnormal in acute HIV. CBC is typically abnormal with here's typical viral type picture. LFTs could be elevated. And often people with an acute HIV syndrome can have atypical findings in the cerebrospinal fluid, typical of viral meningitis. But again, oftentimes if you're not thinking HIV,pPeople have been frequently diagnosed with viral meningitis and sent home.

(21:33):

So let's take a look at an algorithm for acute HIV screening. If a patient presents to you with fever, if they have cough or nasal congestion. If they do, then acute HIV is less likely, it's uncommon for acute HIV to present as a cough or nasal congestion, but still you do want to ask about high risk sexual or needle sharing in the past eight weeks. If they have had a risk, then you still want to consider acute HIV infection. If not, no, we'll treat the underlying infection. If there's no cough or nasal congestion, then we want to look for the presence of typical signs and symptoms of acute HIV. So is there a rash? Is there pharyngitis? Is there lymphadenopathy? Arthralgias? Mucocutaneous ulcers? Is there headache? Is there meningitis? If yes, then definitely you want to screen for acute HIV. If no, if there's no presence of

these things and even if there's no cough or congestion, you still want to find out if they've had any risk. And if there has been risk in the last eight weeks, then you still want to consider screening for acute HIV.

(22:53):

What are the advantages of initiating antiretroviral therapy during acute infection? This has been a question that's been studied over many years, and for a long time we knew that if we treated somebody right away, we reduce their HIV viral load and we reduce their transmission to new partners. So that's obviously one benefit, but there's been more and more evidence that in fact, we can preserve HIV specific immune function. And we can promote the survival of CD4 cells involved in the initial response to HIV. By suppressing that initial burst of viral replication, we're decreasing the magnitude of viral dissemination, which reduces the reservoir size and may preserve gut-associated lymphoid tissue. Although the gut-associated lymphoid tissue gets infected very, very early in this process. There is a potential reduction in the emergence of viral mutations. One of the things that happens if you treat very, very early is you're not giving HIV a chance to diversify. HIV is a very error prone virus in its replication cycle, and even in the absence of treatment, chance mutations do occur by error. And so by treating very early, you're preventing the emergence of viral mutations that can then come out later when there is a selective advantage to those mutations when a patient is on treatment. You also have the potential to reduce the severity and duration of acute illness during the symptomatic phase. Then you also have the potential to reduce the risk of HIV superinfection, which is reinfection with a second strain of HIV. Reinfection with a second strain of HIV is probably not very common, but when it does seem to happen more frequently when it does occur, is in the first year of infection when the immune response is really first being developed. Reinfection is probably a rarer occurrence after the first year, but in the first year of infection people seem to be more at risk for superinfections with another HIV virus.

(25:09):

How does the AIDS Institute recommend we treat acute HIV? So the recommendations from the AIDS Institute are that clinicians should recommend ART for all patients diagnosed with acute HIV infection. At this point, we're recommending HIV treatment for everybody, right? But I think it's particularly important to recommend ART for all folks diagnosed with acute HIV infection and really the earlier the better, you want to get them started right away. You want to get them started as soon as possible if you want to preserve some of the immune functions we were just talking about. Clinicians should inform patients about the increased risk of transmitting during acute infection. We know that this is when they're at their most infectious. We really want to talk to people about their risk at this time. As part of the initial management, patients diagnosed with acute HIV, if you're not an HIV experienced clinician you should consult with one in terms of the care and also obtain a baseline genotype resistance testing, regardless of whether antiretroviral therapy is being initiated.

(26:19):

Antiretroviral therapy should not be withheld while awaiting the results of resistance testing. Really you don't want to waste time here. You want to test and treat, that is actually generally the

recommendation now with rapid start anyway. Particularly important in acute HIV, we don't withhold treatment while we're waiting for the result of resistance tests. We can always adjust the regimen once the resistance tests are available.

(26:50):

What should we initiate with? Well, since we don't have a genotype back we do want to initiate medication with a high resistance barrier regimen that will include either a boosted protease, typically darunavir with tenofovir and FTC/3TC or you can use an integrase that has a higher resistance barrier, dolutegravir or bictegravir with tenofovir and FTC/3TC. As I said, this regimen can be adjusted once the genotype results are available.

(27:26):

Wow. This took a lot less time than I expected it to. So we will have a lot of time for questions or you'll have more of your lunch to yourselves. Alright. So in summary, early infection is disproportionately responsible for forward HIV transmissions. If we can find people early, we can prevent up to 50% of new HIV infections. We have to keep acute HIV in the differential. Acute HIV infection presents with a symptom complex that may be recognized with a high level of awareness. Fever, rash, pharyngitis, oral/analulcers, think HIV. Include it routinely in a differential of all folks with fever. You want to make sure you're ordering the appropriate tests. Diagnosis at the earliest stage of acute HIV infection requires an HIV viral load test, because the HIV antibody test is negative at the onset of symptoms. And HIV antibody fourth-generation tests are definitely increasing our ability to diagnose people during early and acute infection. You can always get expert guidance on any of these treatment questions or diagnostic questions by calling CEI. It's an excellent resource. And if you're interested in a free training on HIV, Hep C, PEP, PreP, or STIs, please visit www.ceitraining.org. Alright. And now we'll open up to questions.

(29:20):

We do have time for questions. If you could please post them into the chat box. Just curious, how much do you think has changed?

(29:49):

I think there's more recognition. I think some of the diagnosis is happening by chance because we're getting fourth generation tests, and those fourth generations are positive and the confirmatories are negative. So we're definitely catching more acute HIVs just in our routine testing using better tests. But I think there is, certainly from the first time that I started doing these talks, there's definitely more provider awareness and people are getting viral loads. But I think that we're still seeing people, I saw somebody just very recently who had the same exact presentation as the first patient I presented who did present to an emergency room with the symptoms that I discussed and and HIV viral load wasn't drawn. So it's still an issue.

(30:30):

Do you think we're doing a better job in emergency rooms now with acute infection diagnosis?

(30:36):

Definitely more than it used to be. But we still have a ways to go. I think it's still provider dependent. You still have to have it in your differential. In more and more emergency rooms the providers are doing that, but it's not universal.

(30:48):

I'm just curious. I may have missed it when you were talking about it, but is there any like slight symptom where someone might not click on to this could be acute infection?

(31:01):

I think the hardest thing is when somebody presents with a mild fever and a mild sore throat, you know we all think, 'Oh, viral syndrome' and that's right, it is a viral syndrome. And most often those are going to be just respiratory viruses or something not that specific. But if somebody has just a fever and sore throat, not all the other symptoms of like nasal congestion, cough, that should start leading us down a path of acute HIV infection. And even if that fever is mild and that sore throat is mild, sometimes we're thinking, 'okay, so viral pharyngitis, strep is negative. It's just a viral pharyngitis.' But HIV is a viral pharyngitis. So you don't have to have, I think it's easier to make the diagnosis when somebody has a fever of 103 and a pounding headache and a rash and a sore throat, that makes it easier. But when somebody has these mild symptoms, we need to be asking people about risk for HIV exposure in the prior eight weeks.

(31:59):

Okay. We actually have a question, we have two. So first Gail thanks for submitting Scott's. I'm going to go with Cindy first. She put in, do you know what the 75% mark is for the HIV RNA test? 99% is like 33 days.

(32:19):

So 99% is 33 days. That number has not been determined. So that's why I lifted off that graph, unfortunately. I think I would love to know what the three quarters mark is. We only know the 25, 50 and 99% mark. Those studies are done by using known seroconverters and banked serum and running these tests over time. And it's very, very hard to know. It's hard to run those tests, hard to determine, but this is our best determination and we don't have a 75%.

(32:54):

Okay. Scott, thank you. You mentioned that primary care and emergency room providers need additional training, but more and more people are going to urgent care walk-ins.

(33:06):

Absolutely. That's a really, really important point. I mean City MD is one of those. That's very commonly, I know every day I get referral consult reports from patients might have gone to City MD when they couldn't get in to see me. I think it's really a good idea and important that the state include trainings in those kinds of settings, because I think there are a lot of folks are showing there first, when they can't get in to see their PCP. They're walking into the local, whatever the local urgent center is. And that's a very excellent point. At our center, I did do a study several years ago, what I did was I looked at our folks who had recently been diagnosed with HIV. And then I looked back, of those who had a recent diagnosis of HIV, how many had a negative test in the last six months? And then I looked through all those charts individually to see how many people had potentially presented with signs or symptoms of acute HIV infection. And there were a number of people who did, and we did quite well in finding those people at our site. Now we're at an LGBT center that has a very high index of suspicion for everybody. Fever is acute HIV, unless we prove it otherwise. But even at our center, we had a number of misdiagnoses and those misdiagnoses were typically things where people thought it was a "viral syndrome." And oftentimes it was a viral syndrome and the person didn't ask about risk. And of course, after the seroconversion when people were asked, we found out that there were clear exposures in that acute illness time. But it had just not been asked. So asking anybody who has a fever, asking for potential exposures is super important.

(35:00):

Actually this is kind of a question for CEI, so I'll answer it. Wanting to know if CEI, if we market our education ie. public service announcements. And how to reach urgent care providers to educate them. We actually do, Dr. Vail has assisted with that as far as training other urgent care providers and other providers as well, primary care included. So we are always reaching out to these centers. We have actually worked with City MD to provide them with trainings around HIV testing and acute HIV knowledge. Some of the questiond I'm asking are redundant, they might be. Please submit more questions. We do have time for our CE credits, so if we can think of something, please submit it. I guess the thing is now, should we be at a point where we're waiting for people to be acutely infected instead of just routinizing the testing itself? I mean, would that change things? If we were really routinizing our testing that maybe we would not have to wait until they're acute?

(36:23):

Absolutely. Routinizing HIV testing is the best way for us to drive down HIV rates, right? Because if we're just looking for signs and symptoms, we're missing all those people with chronic infection and doing a fourth generation test also will help us to find more people. I think routinizing HIV testing, the offering of HIV testing on a regular basis is the key to ending the epidemic. We're in this process now of trying to End the Epidemic in New York State and clearly, finding those folks with early infection is a big piece of that because those are the folks who are responsible for the most new transmissions. But also just finding everybody in the community with HIV is going to be a huge step forward, getting them on treatment. If they're negative, getting them on PrEP. I mean, PrEP is obviously a major issue. Our guy unfortunately declined PrEP at their last visit. So one of the things we're doing is trying to evaluate when people are declining PrEP, what's behind that? How can we change the barriers to access? How can we change either our own barriers that we create for patients, but also what are the issues that patients are

worried about, concerned about feeling when they're saying, no, I don't want PrEP to prevent HIV. Is it they don't perceive themselves as being at risk? Are they worried about the PrEP and the potential side effects of that? What's working for any individual when they're declining PrEP when we know that they're at risk of HIV?

(37:58):

Great, this might seem like an off ball question, but if you are reviewing someone who potentially is acutely infected, what happens if they refuse an HIV test? Like how can you kind of talk with them to make them realize it's in their best interest to move forward and get tested?

(38:19):

That's a really good question. We have people who actually, people come to us who are late stage HIV, right? Who come to us with PCP pneumonia come to us with AIDS manifestations. And oftentimes they have declined testing over the years, knowing that they're at risk of HIV but fear of HIV. So fear of HIV itself, stigma of HIV, does prevent a lot of people from testing. If you have somebody in front of you, who's declining an HIV test, particularly if they're acutely infected, trying to find out what is behind that fear is really, really critical. What are they worried about? You know, is it internalized stigma? Is it their own fears of HIV? You know, what is driving them? What is keeping them from taking that test? Explaining to people that some people have an old image of HIV, HIV means death and I don't want to know that I could die. Some people see HIV as taking tons of pills and getting sick. So sometimes people are declining testing because they're worried. And the more we can educate people about what has changed so much and how we can manage and treat HIV as a chronic infection, I think more people will agree to testing. It's all about education and de-stigmatization to help people agree to, I think, testing and agree to treatment,

(39:42):

Great. We're talking a lot more about rapid initiation, so that's really going to come and curtail with acute HIV infection. Certainly discover it. You know, how well is it moving along to find that person who's acutely infected and rapidly get them started on ART?

(40:06):

I mean, that would be a question for other folks around New York State. Certainly at our center, if somebody tests positive with a rapid test at our site, the day they come in we use a different than rapid test. If that test is positive, we start treatment that day. While the confirmatory test, that's a presumptive positive and we'll start the medications that day, even without lab based testing coming back. If we have a discrepancy between the two tests, we'll send off an HIV test. And that usually comes back in 24 to 48 hours. If the fourth generation test is positive while we're waiting for the rest of the tests, we'll start. If we have a high index of suspicion, we'll start treatment. So we start treatment almost immediately. And I think rapid treatment initiation at the initial visit when somebody has a confirmed HIV test, starting treatment right away is tremendous for so many reasons. One is, of course, decreasing community viral load. As soon as you drive somebody's viral load down, the less likely they are to

transmit to others. There's also a benefit to the person. What we're seeing with rapid treatment is that people feel a sense of empowerment. Like they're doing something, 'I just got diagnosed with HIV, but I'm doing something, I'm going to fight HIV.' People who get same day initiation of HIV treatment have been proven to be more likely to engage in care, come back and get to undetectable quickly. So rapid treatment is really key.

(41:30):

That's excellent. Something that I imagine could dovetail into how we look at acute HIV infection as well as others. There's a lot that we're looking from the state level around women and HIV, particularly PreP for women. And I do think there are still things that people should take into account when they might be dealing with cis woman, as far as discussing with them that they might be acutely infected when they might not be what a provider should look for. Like when they're talking to someone who's maybe that suburban mom who doesn't think she's at risk, she might be presenting as acutely infected.

(42:14):

Yeah. I think a lot of providers routinely test people they know to be at risk and don't routinely test people they think are not at risk because they're monogamous. I think one of the things we are trying to advocate is routine testing for everybody. Because even that monogamous suburban woman, the person that they're with is not necessarily monogamous, not necessarily not injecting drugs. So it's really important that we routine testing be for everybody. A lot of people are diagnosed late, are a lot of women are diagnosed late because of assumptions. You know, a lot of people will say are you monogamous? Yes. Then basically they're taken off the table as being at risk for HIV. So many women come into care very late. And that's a huge issue. So routine testing for women is a very important point. That's very true. And it's also just being aware that transgender women are much higher risk. So really having a very high index of suspicion in transgender women, men who have sex with men, but really it's everybody. More suspicion of folks at higher risk, but really we have to think about it in almost everyone.

(43:24):

I guess it comes down to de-stigmatization, while we've done great at targeting the groups we know to be at highest risk, how do we then introduce those who might think themselves at low risk to go ahead and move forward, because this is just the norm now. And you should all be considering this for your patients.

(43:52):

Yeah I think it just is what it is. It's really, generally people who perceive themselves to be at high risk are much more likely to take PrEP, but there are enough people who perceive themselves not to be at high risk who actually are. And that can become much more of a challenge. Routine routine testing here is really the key. And also again, I just want to reiterate something I was talking about earlier, knowing what tests you're using in your clinic is super important. If you're using a fourth generation test, great, but still know its limitations, know the window periods of that test and know that even if that test is

negative, you're going to want to go and get a viral load. If you're using a third generation or even a second generation test, it's that much more important. So you get a negative test. You really want to ask somebody if they've had any potential risk in the last six to eight weeks and get more definitive testing. You need to know test you're using. And if we tell somebody they're HIV negative, we want to make sure that they're truly negative when we are telling them that. We need to give them the caveats of what the window period that they could still have HIV if their last exposure was X time ago.

(45:10):

Okay. Still trying to figure out a couple more questions, we still have more time for our CE accreditation.

(45:17):

It went much more slowly when I was at home.

(45:24):

And you did mention that Callum-Lorde is a big spot. I don't know if you're going to have this information or not, but I'm going to throw it out there because we were just discussing women and suburban white women. I know that like Long Island and some other suburban areas for a long time have always been very hotspo, they're not the cities, but you should keep an eye on these areas. Is there anything where as far as has that gone down, should any of our attendees today who might not be related to the Bronx, New York City, or even if someone is on the other coast or a major city, but they're upstate, they're rural. What are we seeing in terms of that? Do you have any data as far as you would know?

(46:16):

I don't know. I'm not that much involved in epidemiology. I do think that HIV is everywhere and particularly now with the opioid epidemic, it's becoming more and more of an issue. And so we're seeing, I think we are seeing a rise in various communities and injection drug use as a cause of HIV infection. So I think we all need to be vigilant in doing screening and diagnosis.

(46:57):

What do you think as far as acute infections go, have we seen any changes or ups and downs as far as we know that MSM or Black women would go up and down, where are we standing with them right now? Are we seeing shifts, like we're seeing shifts because of the opioid epidemic?

(47:23):

So the rates of HIV are declining in most groups, which is great nationally. Including MSM, including women, heterosexual men, including injection drug use. However, it is rising in young MSM, particularly young MSM of color. So even though there have been great achievements being made with treatment as prevention. So treating HIV, getting people to undetectable because as we've all been saying undetectable is untransmittable. Getting people diagnosed and undetectable is super important, and

that's been actually showing fruit. We're seeing declining rates in all of those communities, but we're seeing rises in young MSM of color, but we're also seeing rises in hotspots in the South. The CDC is really trying to focus on particularly people of color and African American men and women in the South as being at an increased risk of transmission and higher rates of transmission. So there are areas of the country and certain communities and communities where injection drug aside, communities of MSM, particularly young MSM and other communities of color where there's higher rates within the community that are being targeted for prevention.

(48:40):

And when we talk about young MSM, what's that age range?

(48:43):

Like 24 to 28 is the highest, but really I think it's 21 to 34. But the highest rates I think are like 23, 24 to 27, 28 are at particularly high risk.

(48:58):

Real quick, Cindy wants to know about slides being made available. Dr. Vail has told me that we could share the slides and a PDF version. So just email me, if anyone's interested in those and I will send those over to you. I did have something around testing that would just come up and I don't know, thinking you might run into it. Some of the aspect for when we talk about youth, we've lowered like consent for testing. So I guess how does that now play? If someone comes in where the mother thinks the child has the flu, but you want to discuss possible acute infection?

(49:40):

First get mom out of the room. So adolescents are able to consent to testing without parental consent for HIV, but obviously you need to get that adolescent in the room by themselves and ask for their permission. And you might ask permission to discuss that with their parents, but obviously you wouldn't let a parent know that you're testing for HIV if the adolescent declines that permission. But yes, so adolescents can under the age of 18, you can still consent HIV testing without parental consent.

(50:16):

Okay. Someone has something to say. Good. We're seeing a lot more primary syphilis and other acute STIs nowadays, advice on testing or asking screening questions for acute HIV?

(50:35):

Yes we are. We're also seeing a lot more primary HIV infection, primary and secondary. So yeah, so obviously general ulcers are part of the potential of acute HIV. I think if anybody has primary syphilis, they're almost by definition likely at risk for HIV as well. Anybody who presents with an STI is somebody who should be offered HIV testing at that visit. We want to do routine HIV testing, but we also want to do targeted HIV testing. Obviously anybody who presents with an STI should be tested, but just keeping

in the differential that somebody who presents with a genital ulcer that could be primary syphilis, but it also could be acute HIV infection. You want to ask for dates of last exposure, when exposures happened how they occurred. And then depending on the timing of their most recent exposure, see if they have symptoms or other signs of acute HIV infection and look at their bodies, ask targeted questions. And then order the appropriate lab tests in that kind of case, if you have a rapid test in the clinic, anybody who presents with an ulcer I would do a rapid test in the clinic. If that rapid test is negative, I would send off further testing. If the last exposure was recent, I would send off a viral load. If the last exposure was over a month ago, a primary syphilis chancre could stick around for several weeks. So if the last exposure was over a month ago, a fourth generation test should be enough.

(52:12):

Great. We still have a couple of minutes, but I'll start closing out. If anyone has any questions, please feel free to type them in. We do still have some time. I do want to thank Dr. Vail for presenting on acute HIV today. And thank you for rolling with all of my crazy questions. So again, today was credited for CME and CNE credit. When we are done, you will receive emails on how to go in and evaluate and claim your CE credits. If you have any questions, please feel free to reach out to me. Whether or not you claiming CME or CME credit, please go in and do your evaluations. We are funded through the New York State Department of Health AIDS Institue Clinical Education Initiative, so your feedback really helps us in getting back to the state and it helps with our funding for the future. So please make sure to do that. You will also be receiving information, seeing information about next month's 'This Month in HIV' for June, which will be Caring for the Aging Patient with HIV. Until then, it is going to be Memorial Day. And as I said, I hope everyone is seeing some sun today, and I hope you all get to enjoy your Memorial Day and we will see you again in June. Thank you very much. Have a great day.

[End]