ACUTE HIV INFECTION Rona Vail, MD Lead HIV Clinician Callen-Lorde Community Health Center
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Clinical Education Initiative [email protected] ACUTE HIV INFECTION Rona Vail, MD Lead HIV Clinician Callen-Lorde Community Health Center 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. 1 (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 2 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.