What HIV does to us, and how we treat it

What happens inside the body when infection occurs, and how do the drugs we now have combat the virus? The University of Cambridge's virologist, Jordan Skittrall…

乔丹——有三个麦n ways HIV can get into the body. The most common is by sex. It's usually sexually transmitted. It can be transmitted directly from one person's bloodstream to another, if they come into contact in some way. That can be via blood transfusion or by injury. And the third way is that it can be transmitted from mother to baby. So vertically.

Will - Once HIV is inside the person's body, where's the first place it heads towards?

Jordan - HIV infects a number of cells, mostly cells that circulate around the blood. The most important of these eventually is a class of white blood cells that we call T cells. What it does is it goes into those cells and archives a copy of itself in the genetic material of those cells.

Will - What's the plan then? What's it trying to do?

Jordan - It does two things from that point. One is it then uses the cells own replication machinery to make copies of itself that then come out and go on to impact other cells. But not all of the HIV does that. Some of it becomes archived within these cells. So some of these cells form part of the immune system that provides our immune memory and our bodies are set up to keep a stock of those cells in the archive so that when we respond to new infections, we have the memory available. So HIV can use the body's own way of keeping that record alive to keep itself working.

Will - What does HIV do once it has gained the ability to self replicate within our T cells?

Jordan - It just keeps on infecting more and more of those blood cells without any intervention. This is where it can get slightly confusing because it's possible for the immune system to react against that, against infection of the immune system. But a lot of the disease you see from HIV in late infection is as a result of the immune response taking out some of your own immune system and there's this sort of tug of war back and forth between making more of the cells to keep your immune system functioning and HIV infecting them. So that can carry on for a while until late on in infection where the HIV is beginning to win the tug of war, as it were, so that there are fewer and fewer of those T cells to in fact the white cells to infect.

Will - If HIV is effectively decimating our white blood cell count, our body's immune response, that must mean that the body is severely immunocompromised. Is that the case then? Does the problem become other infections and diseases in our body that previously we wouldn't even have blinked at are suddenly much more problematic?

Jordan - Exactly. So some of these things are infections that we don't even know about. We probably didn't even notice when we got them in the first place. They just live happily with us and we keep them under control. Sometimes they are environmental infections, so things that might just be wafting around on the breeze that have come out of the soil. But again, we normally just keep it under control.

将与所有这些阶段,可能不ved in the infection, we've got a lot of stopgaps that allow us to sort of chuck in an inhibitor or a drug that stops the virus from working at a certain stage.

Jordan - So there are a couple of classes of drugs that will act against HIV when it's trying to enter the cell. Some very important classes of drugs that stop HIV making copies of itself to integrate into the host genome. We have drugs that stop that integration step and we also have drugs that stop the final preparation of the proteins within the virus particle.

Will - Presumably then why throw one of these at the problem when we can throw all of them at the problem?

Jordan - We tend to throw two or three of them at a problem usually when we see somebody. And the reason for that is HIV mutates really rapidly. In somebody who's infected with HIV, there's an entire population of just slightly different versions of the virus. And if the virus is being exposed to a drug but not being completely suppressed, then it is possible for some of those mutated virus to get around single drugs. So what we do is we give the drugs in combination so that the virus cannot overall get round the lot of them, which means that we can keep it under control.

Will - Now as with any virus, HIV can mutate. Is that why HIV is so difficult for the body to find and could it even be a problem for treatment drugs as well?

Jordan - The main problem isn't so much that HIV can mutate around immune response, although it does do that, but the immune system can respond in kind. The problem is, because it's archived itself within the cells, some of which are being maintained as a population for decades, if not the entirety of someone's life. The difficulty is that when it's just sitting there within the DNA in someone's cell and not making a new virus, there's nothing to see for the immune system. So even though you can respond to the cells of the making active virus, there's still this reservoir of cells that are sitting there just waiting for their moment to start replicating at which point you might be seeing virus coming out again.

Will - And that's why, for all the wonders that this treatment does, it's not a cure because if you stop taking these drugs three weeks later, suddenly it's back.

Jordan - Yeah, exactly. It's a really effective treatment and it can keep the virus under control for the entirety of someone's life, but you have to keep taking the pills.