Diagnosing HIV - Concepts and tests

- [Voiceover] So how do you diagnose HIV? I mean, normally when you're feeling sick, you can just kind of go to the doctor and tell them your symptoms and they might just be able to diagnose you on the spot. But diagnosing HIV isn't quite that simple. And the reason why is because its symptoms are really non-specific. So in other words, they're pretty general symptoms. So you might just feel like you have a really bad flu. You know, you might have, you know, a headache or maybe some muscle pains or joint pains or you might have a sore throat. I'm sure every one of us has felt that way in the past. But that doesn't mean we have HIV infection. So since we can't diagnose HIV on symptoms, then how do we do it? How do we make a diagnosis? Well, we do blood tests. So we look for a few different compounds within the blood. So we can look for antibodies that we've made against the HIV virus or we can look for bits of the virus itself, maybe some of its enzymes or its proteins or some RNA. So after an HIV infection happens, actually let me draw a graph here to help explain this. It may be useful, so here is our x-axis. And we'll put days down here. And we'll say day zero is when we got our infection, right. I will go to a few months here and then we'll, a few years down here. So after exposure to the virus our immune system is gonna kick in, right. It's gonna kick in and start to make antibodies. And it takes about a month or so for most people to start making antibodies. And looking for these antibodies, right, testing for the presence of these antibodies is the most common way we diagnose HIV. So look here, you see the antibody level start to rise about a month after infection. And then they drop a little partially because remember HIV disrupts our immune systems, right. So they get in the way of how we make our antibodies. But then the numbers start to come back up a bit. So we're starting to get a handle on the virus. So for the time being, more immune cells can remain alive to be making antibodies. And you know, back in the day a few decades ago our technology wasn't as good as it is now. And someone would have had to have been infected for almost two months before we could start to detect antibodies in their bloodstream. So back then, someone might have come in to get tested for HIV before this two month period, and they might be told that they didn't have HIV when in fact they did. So during this two month window period, there's a risk of getting a false negative result, a negative result despite truly having an infection. And this is problematic for two reasons. I mean, obviously we don't want to get the diagnosis wrong. But also, people in this stage are the most infectious, right at the beginning when the infection is just sort of established. But luckily, these days we've got better lab technology, better antibody tests that let us pick up on these HIV antibodies a lot sooner. So now instead of two months we can detect antibodies almost as soon as they start being produced. So let's say for example it's like a month in, just like on this graph, although it can take longer to produce antibodies. But let's say it's about a month. That'd be about average. So we can detect them earlier, not because we're making antibodies any faster these days. We're just better at detecting their presence within our bloodstream now with our tests. So you see, our window period that you might get a false negative in now has also decreased. So that's good. So those are antibodies. That a way of diagnosing an HIV infection, by looking for stuff our immune system has produced, right. But there's actually this other test that's often done at the same time as these antibody tests. And this test is one that looks for an HIV specific protein called P24. So there's this protein inside the virus called P24. And you can see its concentrations do rise and fall fairly quickly here. Right now I'm drawing out the blood levels that we typically see of P24. So testing for it actually presents an interesting issue because on one hand it's great that we can potentially detect it even earlier in an infection than we can detect antibodies, right. So the window period is smaller, about two weeks now. But on the other hand, you kind of have to get tested really early on to detect it or you'll miss it. And that's tough to do when you don't really have many symptoms. And by the way, the reason the concentration falls off here is because once our antibodies start to develop, right, you can see them sort of going up here, they bind to the P24 antigen and form these little complexes which aren't really detectable using our standard P24 antigen test. So let's say for argument's sake that you do test positive on either the antibody or the P24 test or both. What happens then? Does that mean you definitely have HIV? Well, there's a system of double checking just to make sure. So these antibody tests are done by a process called ELISA, enzyme-linked immunosorbent assay. And that's a huge mouthful of words. But essentially, all that means is it's a lab test that mixes our blood sample with some enzymes and some other antibodies that actually detect, that they stick to HIV antibodies or to the P24 protein. So let me give you some scenarios here. So let's say you test negative for these things. Well, in that case you can be fairly certain you don't have HIV. And based on your risk factors for HIV infection, you can just get tested again in another three to six months or so if you feel you're at high risk. But if you get a positive ELISA test, we want to just double check that result, right, just to be sure that it's the HIV virus that's actually causing the positive result because believe it or not certain conditions like Lupus, you may have heard of Lupus, or diseases like syphilis can cause this test to be positive. So to really specifically test your blood for HIV, your blood will then move on to a second test, a Western Blot. And this Western Blot test specifically tests your blood for actual viral proteins. So let's say this is our Western Blot testing strip here. We're essentially looking for the presence of some of the proteins that are on the viral envelope so maybe some GEP120 or some GEP41 and so on. And we also look for specific proteins that HIV makes. So for example, some of its enzymes, like its reverse transcriptase or its integrase. So the Western Blot test is just a double check that can detect for actual viral proteins to make sure it's HIV and not something else that's giving you a positive ELISA test result. And so bringing you back to overall diagnosis, so if you have a positive ELISA and a positive Western Blot, then a diagnosis of HIV is confirmed. There's a 99.99% chance that you do have an HIV infection. But if your ELISA was positive and your Western Blot was negative, then the ELISA, at least for HIV, was a false positive. So there's a super high likelihood that you don't have HIV. Remember there's some other things that can make the ELISA report positive when it actually isn't. But for the most part, it's still about 99.5% accurate for HIV. And of course, if your ELISA was negative, then again really, really unlikely that you have HIV, unless of course you were in the window period when you got tested, in which case it'd be pretty important to get tested again after about three months or so when your antibodies would have time to have developed. So the last thing I want to mention is that it's important to know what subtype of HIV you're dealing with. So we've got two slightly different types of HIV virus. We've got HIV-1 and HIV-2, with number one being the most common by a long shot. And they're both pretty similar to each other. They cause the same illness. They just have a few different proteins and a few different enzymes here and there. And you know, the main reason you'd want to know what type you're dealing with is because some of the standard drugs we use to treat HIV-1 don't work very well for HIV-2. So we wanna know which one we're dealing with. So we look for their RNA. And that's great because not only can it tell us whether we're dealing with HIV-1 or 2, but it also becomes detectable really early on in an infection, from about day 12. So now our window period potentially can be really small. And so we look for this RNA via nucleic acid testing, NAT, which is not the same as the ELISA or the Western Blot that we saw before. This is a special kind of test that can find tiny amounts of HIV nucleic acid in our blood sample. And then when it finds them, it amplifies them and makes lots of copies of them so we can detect that they're there. So the last thing I'll mention is that there's something called a rapid HIV testing, and that's becoming more and more available in more and more places. And that makes testing quicker and easier to do. So more people can get tested. And they're pretty simple. They're not a give-a-full-vial-of-blood sort of test. All you have to do is just get a swab inside the mouth or a finger prick test, just to get a little bit of blood. And the other awesome thing about them is that you can get your results in only about 20 minutes, whereas the tests I mentioned before all take a few days to a week to get your results. So these rapid HIV tests, they work by the same ELISA method I talked about earlier. They check for the presence of HIV antibodies and P24 protein, which you can detect in your saliva and of course in your blood. So the slight issue with rapid test is that even though they're quick and they're easy and they're cheap, their accuracy is a little bit less than the conventional test we talked about earlier. So they're more of a screening test than a diagnostic test. In other words, they're really, really good at detecting true negatives. So if it comes up negative, it's highly likely that you do not have an HIV infection. But if they come up reactive or positive, then you'd have to go through the conventional diagnostic tests to confirm or deny these results, right, just to make sure.