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Charles: This is Charles Prober. Morgan: And this is Morgan Theis. Charles: And now we're going to talk about the interaction between tuberculosis and HIV, human immunodeficiency virus. We're going to talk about this because the two actually commonly occur together in different parts of the world, and one infection makes the other one typically worse. Together, they create what one might refer to as a "perfect storm." The stick figures which you've drawn show nine individuals on a top line, one of whom is colored in a different color. This is meant to depict the roughly nine million people each year who are infected with tuberculosis, one of whom, or about 13%, is co-infected with HIV. That's a very large portion of the population for which this is a problem. It represents over 1 million people. The stick figures beneath are meant to depict death caused by tuberculosis. There are three individuals depicted here that represent the roughly 1.5 million individuals who die each year from tuberculosis. And about 1 in 3 of these individuals is co-infected with HIV. So the combination of HIV and tuberculosis is incredibly important. In very general terms, each infection makes the other one worse. In other words, if you're infected with tuberculosis and you are or become co-infected with HIV, the tuberculosis infection becomes more severe. It is more likely to be disseminated. It is more likely to be associated with severe necrosis of the lungs or miliary TB or TB meningitis. So HIV makes tuberculosis worse. Morgan: So almost in every way. Charles: Almost in every way. Morgan: Right, OK. Charles: And similarly, tuberculosis makes HIV worse. Through mechanisms that are not clear to me at least, being infected with TB makes the HIV virus proliferate more and makes the progression of the HIV infection more severe, so they are mutually bad for each other. Morgan: So this why we call it "the perfect storm." Charles: Precisely. Now clearly, ultimately, you have to treat both infections because they're both bad infections. Morgan: Right. Charles: For tuberculosis, we will be talking about the anti-tuberculose drugs to use in another video, but you do have to use the anti-tuberculose drugs. With HIV, of course, you have to use antiretrovirals in order to control the infection. Morgan: Right. Charles: So it's a given that you have to treat both infections. But another part of the perfect storm is that when you begin to treat, you may have an adverse effect in something called the "immune reconstitution inflammatory syndrome." It's abbreviated IRIS. Morgan: OK. I was going to say that's a big word. Charles: It is a big phrase. IRIS stands for the immune reconstitution inflammatory syndrome. In order to describe the effects of IRIS, I'm going to talk about two hypothetical patients infected with tuberculosis. Morgan: OK. Immune reconstitution inflammatory ... Charles: Syndrome. Let's imagine one patient infected with tuberculosis and it's a latent infection. It's a quiet infection. It's a sub-clinical infection. In those patients, when you get infected, if you're infected with HIV and you recognize the HIV infection and you begin to treat the HIV infection with antiretrovirals, the TB infection may become clinically manifest. It is uncovered. That actually is referred to as "unmasking IRIS." In other words, the treatment of the HIV with antiretrovirals, presumably because you reconstitute the immune system, makes the TB infection become evident. That's called unmasking IRIS. Morgan: OK. So before you had this latent TB infection, you might not have even known you were sick as a patient, you get HIV, you still don't know you have the TB, and then you start treating the HIV, and that's when all of a sudden you realize you have TB. You get this clinical tuberculosis - Charlie: Exactly. Morgan: OK. Charlie: So it's unmasked. You recognize it at that point. You then treat the TB infection, and of course, you're in the meantime still treating the HIV infection. That's one hypothetical patient. Another is a patient known to be infected with tuberculosis. They have clinical disease. Perhaps they have the most common clinical disease, which is pulmonary disease. Then you determine that they also are infected with HIV, so you begin, again, treating the HIV infection with antiretrovirals. Paradoxically, as you treat the HIV infection, the TB infection gets worse. Again, it's thought that that results from when you treat the HIV infection, the immune system becomes more robust, because you're controlling the HIV infection, which was previously tamping down the immune system, so the immune system becomes more robust, and as a result of that robust immune system, temporarily, the TB infection gets worse. That's called "paradoxical IRIS." Morgan: Paradoxical IRIS, OK, so that makes me think maybe we just shouldn't treat the HIV. Charles: And of course, that would be not good thinking, not because you said it, but because you must treat the HIV infection because otherwise, it will progress, and the patient will die of HIV. This is a temporary phenomena where you get transient worsening of the TB infection. Then as you continue to treat the HIV infection and you continue to treat the TB infection, they both eventually settle down, ideally. Morgan: OK. This is more something that is interesting and we watch out for because it can be acutely problematic, but that you wouldn't actually change a treatment for. You would just have to be aware of it and eventually, as you treat the HIV, you treat the TB, hopefully, things will actually move in the correct direction (laughs). Charles: Exactly. Then the final thing that I'd like to mention with regards to this perfect storm, this badness between having both TB and HIV at the same time, is that the drugs used to treat each of those two infections may adversely interact with each other. One that is probably the most important adverse interaction to know about is the effect of rifampin, a key drug for treating tuberculosis, on the different antiretroviral agents. Specifically, rifampin is known to be an inducer of important enzymes in the liver that are responsible for metabolizing a lot of drugs. The enzyme system happens to be called the "cytochrome P450 enzymes." Rifampin induces that enzyme, in other words, makes the enzyme more active. That enzyme is responsible for enhancing the metabolism of many drugs, including antiretrovirals, so you end up, when you give the rifampin, causing the antiretrovirals to be metabolized more quickly and lose their effectiveness more quickly. So you have to be aware of that and other kinds of interactions, of drug interactions so that you can modify and modulate your therapy of the infections accordingly. We'll talk about that at another time.