HIV Medicine

Transcription

- [Voiceover] What is HIV, and what is AIDS? Well, let's first look at HIV. HIV is a virus that attacks our immune system, and if we expand this out, we can see that that's reflected in its name: Human Immunodeficiency Virus. So this implies that it does something to our immune system somehow, and we'll actually explore that a little bit later on. And if we don't treat HIV, it'll eventually cause AIDS in the infected person. Acquired Immune Deficiency Syndrome. So right away you already get a sense that HIV attacks your immune system so destructively, that you end up acquiring an immune deficiency system. It puts you into a state of immune-system failure, so you end up not being able to fight off even the most basic infections. And this immune-less state, is what we call AIDS. So let's explore this a little bit further now. Let's actually use the help of a graph, this might be helpful. So here's our graph, and we'll put time down here on our X-axis, and actually just to make this extra useful, we'll put weeks in this beginning part here, and then we'll transition to years here, and you'll see how this is relevant in a few more minutes here so, on the Y-axis here, we'll put CD4 T-lymphocyte count. T-lymphocytes are a really really important type of immune system cell. And CD4 just refers to a type of protein that's stuck through their cell membranes, that's kinda how we like to identify them, by this protein on their membranes. And the reason they get a special spot on an entire axis of our graph here is because they're super important in the progression from HIV infection to AIDS. Because as you might have suspected, it turns out that HIV preferentially loves to infect these CD4 cells of our immune system. And why is this so bad? Well, these CD4 cells, also called helper T cells, play a huge role in signalling your other immune cells to come and destroy every given infectious particle that our body discovers. Like maybe strep throat bacteria, or flu viruses, or even HIV viruses, for that matter. So these CD4 cells are kinda central. They're almost like little amplifiers of our immune system. So because HIV loves to infect and kill these cells, it completely disrupts how our immune systems function, and renders it essentially useless. So let's say you acquire HIV in your body, either in your bloodstream or your tissues, maybe through unprotected sex with an infected partner, that would be the most common method of becoming infected with HIV, in adults at least. What happens? Well, the main thing is that the virus really quickly gets into your white blood cells, so these T-helper cells, the CD4 cells we've talked about. But also some other white blood cells, like your macrophages and so on. And from inside a white blood cell, it can do two things. One, it can sorta hijack your cell's machinery, so it manages to insert its genetic material into your own cell's DNA. And from there it starts to make lots and lots and lots of copies of itself, lots of new HIV particles. Actually that's really really important, so let's put that on our graph too, let's say, "viral load" here on another Y-axis here. Viral load referring to the amount of HIV in your bloodstream. So we can see that after our primary infection here, the viral load starts to increase. It's hijacked our T helper cells, and now new HIV particles are being churned out, and our viral load is majorly on the upswing. And you'll notice that the viral load is starting to rise at around the two to three week mark, and that's just 'cause it takes a bit of time for the HIV virus production to start sort of ramping up within our bodies. And of course a major concern here is well, the more HIV there is in your bloodstream, the more CD4 cells get infected, get hijacked, right? But the biggest problem here, thing number two here, is that HIV infection of your CD4 cells, triggers a self-destruct sequence within these cells. So you end up losing these CD4 cells. And even worse, the self-destruct sequence doesn't just destroy the infected cells, it even destroys nearby immune cells that maybe have come into the area to try to help out. So I won't go into the mechanism in this video, but you do end up losing lots more immune cells than just the infected ones, and that's part of why you see this massive dropoff here, this line representing our CD4 T-cell numbers has this really steep downward slope, we're losing lots of T-cells. While at the same time our HIV viral load is going up and causing more and more infection of our cells. The other thing I wanna point out here is you can see this massive rise in viral load and this pretty massive drop in CD4 levels, and this huge viral load means that this time period right, early on in an infection, is when someone with HIV has the highest risk of transmitting it to someone else. I guess one good thing here is that eventually, maybe a month or so in, your immune system gets somewhat of a handle on the virus, and it starts to make anti-HIV antibodies, right? Those are just antibodies against HIV. So they start to fight off the virus to some extent. And this is called seroconversion, when you make antibodies to something, so now we've seroconverted to HIV. So now the antibodies get to work on helping to destroy the viral particles. And that's why we see this decrease here in viral load in the bloodstream. Because our immune system is starting to control the viral levels to some degree. And this also gives our CD4 cells a chance to recover, to some extent, because there's less virus around to infect them. So you might be wondering, how you're gonna feel during all of this, with this massive battle going on inside your body? Well, you're gonna feel sick, you're probably gonna feel like you're having the worst flu you've ever had. So about here, about a month or so in, at seroconversion, you start to fight the infection. And as a result, most people get some serious flu-like symptoms, so things like headache, and fever, and sore throat, muscle pains, joint pains, some people get swollen glands, just sort of fatigue and feeling unwell. Some people get a rash, some people get some open sores in their mouth. These are some of the more common symptoms of an acute infection with HIV. And this flu-like illness that people experience is referred to as Acute HIV Syndrome. And the reason for a lot of these symptoms is because well, when immune system cells get really active, or when they die off, both of which are happening here of course, they tend to release these little chemical signals that cause inflammation, sort of all throughout your body, and so this is what underlies a lot of these symptoms here. So back to our graph, the immune system can't completely kill off the HIV, even though we have antibodies now, right? And that's because A, remember the rate of immune system killing is roughly matching up with the rate of new viral particles being produced. And B, because the virus has sort of taken up residence in some really really hard-to-reach reservoirs in our body. Like within the brain and within our bone marrow, and within our genital tract. Because of these two reasons, these curves tend to sort of stabilize at some point, they reach a set point, where again, our immune system is killing off HIV at a pretty similar rate to which HIV is replicating. So the curves start to come together a bit more and stabilize somewhat. So this period here is thought of as the start of the second phase of HIV infection, what's called the latency period, or Chronic HIV. This acute infection back here being phase one. So in this latency period, we don't tend to see any clinical signs of HIV illness, the person is often asymptomatic. They're still infectious, but there are few or no symptoms during this phase, and without treatment, this phase will last on average about 10 years. And I said that our curves here stabilized, right? But it turns out that HIV's actually replicating, killing our immune cells just a teensy little bit more than our CD4s are recovering. So over this long period of time, phase two, eventually, again, without treatment, HIV will start to overwhelm our immune system, and we'll start to see symptoms again. So things like fever or muscle pains or swollen glands, really similar to the acute infection, and again, much for the same reasons as before. And many people at this stage of the illness experience significant weight loss. HIV causes you to use more energy than usual, and also prevents you from absorbing nutrients from your food as well as you normally would. So we often see some significant weight loss for these and a few other reasons as well. Eventually, if our CD4 cells get to a critically-low number, and result in our having no functional immune system, that's what AIDS is. Essentially a state of being where we have no immune system. So at this point, this is when certain bugs, bacteria and viruses that would never stand a chance against even a minimally-effective immune system, these things start to infect the person. And we refer to these specific infections as AIDS-defining illnesses, because we just know that if somebody has one of these illnesses, they just cannot have a functioning immune system, it just wouldn't happen, or at least it would be really really unusual. So there's a high suspicion of this person having AIDS and not just an HIV infection anymore if they have any of these AIDS-defining illnesses. Two examples of AIDS-defining illnesses are two fungal pneumonias, one called pneumocystis pneumonia, and one called cryptococcal pneumonia. These are two common AIDS-defining illnesses. And again, these aren't the types of infections that you get when your immune system works even a little bit. So actually one of two criteria has to be met before we can say someone has AIDS. Either they have to have extremely low amounts of CD4 cells in their blood, and to get a little bit technical here, it's if they have less than 200 CD4 cells per microliter of blood, with the normal count, the normal CD4 count in this amount of blood, it should be around 1000 to 1100 CD4 cells. Or, regardless of CD4 count, if they have any of the AIDS-defining illnesses, like either of these, for example, then we can say that they have developed AIDS. And so you might have suspected this, but it's actually the overwhelming impact, and the complications of serious infections that you pick up because of the immune deficiency in AIDS that actually results in the death of the person. So from HIV infection to eventually an incredibly high amount of viral particles, and low amount of CD4 cells in the bloodstream, to development of a completely non-functional immune system in AIDS, very quickly leading to overwhelming infection by essentially every infectious pathogen from A to Z. And because of this, death results.