 Hey everybody, Dr. O. This video we're going to focus in on the drugs that are used to treat HIV infection. Before we do this real quickly, like why does your immune system struggle with it so much? And I think that also ties into why we're having struggles creating HIV vaccines. So number one, the target, HIV is infecting the CD4 positive helper T cell, the general in your immune system army. So without the general, your immune system doesn't function very well. So it's actually attacking the cell that would be responsible for most of our response to fight off viruses. So that's one reason. Number two, retroviruses. So viruses mutate faster than bacteria RNA viruses appear to mutate faster than DNA viruses. Retroviruses seem to mutate even faster. So there's lots of mutation, which means that you're going to see lots of different versions. One person could have millions of millions of variants of the virus inside of them. So another reason it's tricky for your immune system to get at and even for drugs to work is that it actually it crams itself into your genome. So it's hiding inside host cells. So it picked a very important target. It can hide inside those host cells. I mean, that's why it's hiding in your lymphoid tissues and all sorts of things. Like even when people have no evidence of the infection in their blood, their body is still full of these viruses that are hiding inside their immune tissues, their lymphoid tissues. And then number three, this rapid mutation rate makes it hard for drugs to target and your immune system. And then so we'll talk about why we use a combination of drugs. So let's go ahead and look at these major classes of drugs that are used to fight off HIV. So we will use a cocktail, which is H-A-A-R-T or heart, highly active antiretroviral therapy. The main reason you want to use a cocktail is because of that quick mutation rate, the quick evolution of this virus. I always like to say that if you were to choose any one of these drugs within five or six years, it would be worthless. You use a cocktail because you're asking the virus to mutate around several, three, four, five, or more drugs at the same time, much hard to do that. So it's hard to win the lottery, right? But it's very hard to win it three or four or five times. That's what random mutations are like. So that's why you use a combination of drugs. Certainly it's more effective, but it does slow evolution and slows resistance. So let's go ahead and look at some of these drugs. So let's start with the fusion inhibitors because that's where the virus actually finds the cells and fuses with it. So if the virus is in your blood but can't fuse with your cells, it wouldn't be a problem and then it would just die off. So fusion inhibitors are gonna stop the fusion of the virus to either the CD4 positive CD4 receptor or the coreceptor. So there are actually CCR5 agonists. They're working on even more drugs that are gonna stop this fusion process. So this will not be 100% effective, but it'll stop some of the viruses from fusing. The next group, I'll just look at the ones that are on the picture and then I'll talk about a few more. Next, we would have the reverse transcriptase inhibitors. So let's say someone's taking all these drugs. A handful of viruses will get into the cell. Now if you can block most of them from using reverse transcriptase, the enzyme, to turn their RNA into DNA, then they can't move forward. So now we have fusion inhibitors and reverse transcriptase inhibitors. Next at the bottom here, we have the integrase inhibitors. So the handful that have made it in and turn their RNA into DNA integrases the enzyme that would force this viral DNA now into our cells. So integrase inhibitors would stop that process. So hopefully only a handful of these organisms have made it this far. Next on the list, then you have the protease inhibitors. So once the viral DNA is inside our genome and we're producing viral proteins for them now, the proteases would be needed to make functional proteins. So the protease inhibitors should stop that process. All right, so we talked about fusion and cell entry inhibitors, like fusion inhibitors and the newer ones that are blocking the CCR5 co-receptor, we talked about reverse transcriptase inhibitors, integrase inhibitors and protease inhibitors. But now as the cell gets ready to leave here on the right-hand side, we now have maturation inhibitors that would stop this immature virus from becoming a fully mature virus. And the last group would be called the tetherins, where they would actually tether the viruses to this cell, preventing it from escaping and going and finding another cell. So if you're to use all these different treatments, you can see why you greatly slow the spread of this virus, which is why a disease that used to be able to kill in a few years without treatment has been relegated to a much more manageable chronic disease. And this is also why many people that are using these drug therapies are undetected as the term they would use. There's no evidence of the virus in their blood. It does not mean they don't have HIV. It's hiding in their lymphoid tissues, etc., like we've already mentioned. But these drug cocktails work really well and they can control the infection to the point where you can't find evidence in the blood. So all right, so I already mentioned, but I'll say it again, the reason you use a combination or cocktail of drugs is to make the treatment more effective, yes, but also to slow resistance, slow evolution. We'll talk about the same thing with some of these combinations of antibiotics in the same way. Usually when you use more than one antibiotic, yes, it'll help in some extent. But the main reason to do so isn't for that infection. It's to slow the resistance that comes from using antibiotics. All right, so that is the antiretroviral therapies that are being used to combat HIV infection. I hope this helps. Have a wonderful day. Be blessed.