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HAART treatment for HIV - Who, what, why, when, and how

Video transskription
- You may have heard the term HAART referring to HIV treatment. But what exactly does that mean? Well, HAART, which stands for highly active antiretroviral treatment refers to the sort of modern day, present treatment regimen for treating HIV infections. And it's called highly active because compared to the previous treatment regimen, HAART is just a lot more effective and so the name just kind of stuck. So before we give just one type of drug to help control an HIV infection, we usually give an NRTI which stops the reverse transcriptive step and infection of a CD4 cell. But, you know, HIV likes to mutate a lot and it turned out that when only one type of drug was given for an infection, the HIV would eventually become resistant to that type of drug. So, of course, the drug didn't work anymore and the person's infection would almost sort of pick up where it left off it would start to worsten again. Except this time, almost more aggressively in a way because now it would be resistant to that original type of treatment. But in comes HAART, highly active treatment. And you know, it's not that we're using totally different drugs, I mean, sure we've got a few more types at our disposal now, but the key thing is that nowadays we know that if we give two or three drugs, which is what we usually do in HAART. So if we give two or three drugs, instead of just one, the HIV infection can be really well controlled. And what do I mean by that? Well, each of the drugs in a particular HAART regimen works in a slightly different way, stopping HIV at different points during its replication. So these drugs used together are really effective at preventing HIV from making copies of itself. It's life cycle just won't be able to continue, so new varions just don't end up being made. And you know, if we do encounter, by chance, an HIV particle that's resistant to one of the antiretroviral drugs, chances are it wouldn't be resistant to the other two drugs that make up that particular HAART cocktail. And you know it would be really hard for HIV to become resistant to all of the drugs in a particular HAART regimen. I mean, here, let's do some math. Not super hard math, I'll leave that to Sal, but in your body HIV multiplies essentially, and it creates a few billion new viral particles per day. And during replication, it's reverse transcriptive enzymes makes a lot of mistakes, in fact, for every about 10,000 nucleotides it adds on to a new strand of DNA it makes a mistake, and it inserts the wrong base. One in every 10,000 bases is wrong. And it doesn't have a very good repair mechanism like we do for our DNA, so this mistake sticks around. So let's say, for arguments sake, that one of these mistakes affects one of our drugs target proteins within the HIV. Let's say this stretch of DNA here was supposed to code for intergrace. So this virus's intergrace enzyme will still work, but our intergrace inhibitors might not be able to stop it anymore because it's mutated. Well, our HAART cocktail would still be able to stop this mutant HIV because we have other places in the replication cycle that we can inhibit it. So essentially, a virus would have to mutate, either randomly, or sort of evolve by selective pressure to become resistant to all of the HAART drugs that we're throwing at it in a given cocktail. And, in fact, the chance that it could become resistant to all three of the types of drugs would be at the very least one in ten to the twelfth power, that's one in a trillion chance. I'm just multiplying one in 10,000 here by one in 10,000 here, by one in 10,000 here. And, you know, I'm being really generous here, because this is assuming that the one in 10,000 base mutations are even occuring at the target enzymes coding sequence of DNA. So, bottom line here is that it will be extremely unlikely for an HIV particle to mutate during replication in a way that would let it escape from all three of the HAART drugs. And you know, of course, it would be extremely unlikely to thus find an HIV particle just floating around in the bloodstream that's resistant to multiple drugs. Because remember, replication is actually suppressed by taking the ARV, so once you're on HAART, potential mutants aren't even being created anymore. Or, at least a lot less so. So now you have an idea of what HAART is, a drug cocktail, two to three different types of drugs all taken together that A. Makes drug resistance by HIV really unlikely, and, B. That's still able to fight off resistance strains that we might encounter. But you know, there's a few other things to consider with HAART. I mean, for example, who gets HAART? And when is it prescribed during the course of the infection? And, how do you sort of take it? I mean, is it a bunch of pills? Is it an injection? Well, let's start here with who and when. Because you might reasonably think that, you know, everyone who's diagnosed with HIV gets started on HAART right away and you know there's good evidence that that is a good idea. But it gets a little complex because there are some drawbacks to starting therapy early and by early, I just mean before the onset of any symptoms or AIDS defining illnesses, and, you know, these drawbacks need to be considered. For example, there are some side effects of the ARV drugs, such as an increased risk of cardiovascular disesases like heart attacks, or strokes. There's potential problems with bone health too, long term exposure to these ARVs are associated with a greater loss of bone density as a person gets older. More than the normal loss that happens as you age. There can be psychiatric side effects, too, like feeling a bit sort of sluggish in your thinking. And there can be gastroinestinal side effects, too, like chronic diarrhea. So you can imagine that if someone has HIV but they're in the latent phase, in other words they're not having any symptoms, starting them on antiretrovirals might actually cause a decrease in their quality of life at that given time period. The other thing that needs consideration is that, you know, if you do start a HAART treatment regimen then you need to stick to it for the rest of your life, taking your medication every single day without fail. Because studies have repeatedly shown that stopping your ARVs, or not taking them every single day as prescribed, is associated with the HIV in your body becoming drug resistant. So that means that in the future if you decide to start your treatment again, your drugs just may not work as well anymore. They may not work at all, anymore. So when you talk to your doctor about the right time to start your treatment you'll probably go over some strategies to make sure you can take your medication every single day to minimize drug resistance from happening in your infection. And one thing that's helped out in a huge way for people taking their medication every day, is the fact that these combinations of these drugs, remember, you're taking cocktails of usually three of these types, combinations are available in a single daily pill, nowadays, and that makes it a lot easier to stick to your treatment schedule. I mean, a few years ago, and actually still in some countries, you'd have to take a handful of pills every single day, sometimes multiple times a day. And now you can get your whole combo in one single pill, taken once a day, so that's really, really useful. So now we know there's potential problems with starting HAART too early. But you know, when is the right time to start, then? Well, it is a little different for each person, so you'll have to have a chat with your doctor about the right time to start, but there's a few general principles that'll help guide the decision that you guys come to. So for one, we know that if your CD4 T cell count is less than about 350 to 500 cells per cubic millimeter of blood then it's time to start HAART. Remember, CD4 count is sort of used as a marker for how far along the illness is, right? The lower the CD4 count the more damaged the immune system is. Viral load is important too. If the amount of HIV in your bloodstream is higher than 100,000 copies per millimeter of blood, it's time to start HAART. And, I know, the last thing I'll say about this is is if a person is pregnant, if they're a young child, if they progress to AIDS, of, it there's an opportunistic infection or an AIDS defining illnesss present, then regardless of CD4 count, even if you're higher than that 350 to 500 cutoff, HAART needs to be started right away to hep your immune system recover as much as possible.