Immune reconstitution inflammatory syndrome (IRIS) in AIDS

- So let's say this person has extremely low CD4 cell counts, right, let's say it's because of an immune deficiency like AIDS. And you know, let's say they have a really high viral load, as well, right? And we've decided, right, or their doctor, and jointly us and them have decided that it's time to start HAART therapy, right, antiretroviral therapy. So we do. We prescribe the drug and they take the drug and everything is cool, everything is good at this point, right? Viral load is going down, all these viruses are being stopped from replicating, that's great. But what else happens when viral load goes down? Well, I mean this is a good thing, but immune cells are gonna start coming back, right, that's good. CD4 cells are gonna come back, and CD8 cells, and macrophages, and neutrophils‎, and all sorts of white blood cells are going to start being, sort of, recreated in the bone marrow, and they're gonna start being able to survive in the body without being destroyed by the effects of HIV, right? So I want you to think about something here. Well, we're essentially flooding the body now with white blood cells, right? The plan is to get our level of white cells to pre-infection levels, really healthy levels of white cells. But just what was going on when they weren't around, when their levels were really low? Well remember someone with an immunodeficiency they can pick up opportunistic infections. And these opportunistic infections can sort of lay low, right, and they might not cause any outward symptoms. So the person might have bacteria floating around, or viruses, or fungi, but they might not have any outward symptoms. They might not know that they have occult, opportunistic infections, that's what we call infections, or really anything that's not really readily detectable, we call it occult. The problem is, now that the immune system is getting stronger, right, it's reconstituting, so to speak, now we have the tools, right, the fire power to recognize these occult infections, and we might start to fight against them. And when we start this war, right, this battle against these, they might, again, they might be bacteria, or viruses, or fungal infections, our immune cells are gonna release these little chemicals called cytokines and little molecules that create a really inflammatory environment. Which is normal, I mean, that's part of our immune response, and that's kind of one of the mechanisms that we have to call in reinforcements, right, sending out all these inflammatory signals. But sometimes they go overboard, they take it a little too far and they overdo the inflammatory signals. So there are cytokines everywhere, and this might cause the person to have a really high fever. And there's little compounds, that the white little blood cells release, that are designed to damage the bad guys, but they can actually end up damaging tissue, as well. So there's potentially some tissue damage happening. And remember, I said reinforcements are coming in, right, so more white cells are coming in and this cascade is sort of cascading away, right? Well, this whole thing, right, everything I've described here, there's a name for it, and it's called Immune Reconstitution Inflammatory Syndrome, or IRIS. So it's basically a tremendous amount of inflammation, right, systemic inflammation all over the body due to the immune system reacting against bugs that it just discovered upon it's sort of return from low function. So I mentioned that the person is gonna have a fever, right, a high fever, but they're also gonna feel really, really sick when this is happening. You know, it's kind of paradoxical, but they might actually start to get symptoms of the opportunistic infections that they have. They might actually start to get worstening of those symptoms, which is kind of interesting. They're just gonna feel really unwell. So everything I've just described there, that's the classic, sort of, manifestation of IRIS when the immune system comes back and then it realizes, it recognizes that there's all these little bugs running wild everywhere and then it starts up this crazy inflammatory syndrome, that's the usual way that IRIS manifests. But there's also another fairly common scenario that IRIS can sort of manifest as, and this one's a little bit more bizarre. So sometimes some of the T cells that get reconstituted, they get replenished, remade, and are now patrolling around the body. Well, they might run into some dead bugs, or little bits of dead bugs, right? Maybe bacteria, or viruses, or fungi that maybe haven't been cleared out of the body yet. Oten a few weeks previously, the person was infected with an opportunistic infection and they took medication and the bugs all died off because of the medication the person took. But you know, the dead bugs might just not be cleared out yet, it takes a little bit of time, even though they're dead. But these reconstituted T cells, they might mistakenly think that they've encountered a real threat. So again, they kick off the big inflammatory cascade that we call IRIS. So those are really the two most common manifestations of IRIS. Now a few things I just want to touch on before we wrap up here, so, does this happen in everyone? And the answer is no. It seems to only happen in about 20% of people who have just started HAART treatment. And that's kind of interesting in itself, right, I mean, the same sort of thing is happening in everyone on HAART, right? High viral load, and low T cells, and lots of bugs hanging around and doing whatever they want, and then immune reconstitution. So why only 20%? Why not everyone? Well, the answer isn't completely known right now, but it's thought that a couple things can increase the odds of IRIS after starting antiretroviral treatment. So having a really low amount of immune cells before starting HAART, and, having any active opportunistic infections, or high burden of bugs in your system when you do start HAART. And again, these qualities have just been associated with the development of IRIS and you know we're free to hypothesize why, but we can't exactly put our finger on why this is the way it is, as of yet. But in practice, we just try to minimize the risk of things like IRIS happening by treating any opportunistic infections a few weeks before we start anyone on HAART. So the last thing I wanted to say is, you know, what's the prognosis, is the person gonna get better, are they gonna be okay? And also, how do we treat it? How do we treat IRIS? Well, usually the person spontaneously gets better as the immune system gets stronger and stronger. So people usually get better without any extra treatment. But sometimes, just as a little boost, the person might be given antibiotics, or antivirals, against any known bug that they might have. And that's just to help the immune system fight off the infection a bit more easily. And sometimes if the inflammation is really bad, then the person might be given steroids to tone down the inflammation, that's one of the things that steroids do. So that'll sort of tone things down until the infection's been taken care of. But again, in that 20% of people who get IRIS after starting HAART, usually they spontaneously get better without any extra treatment.