Map of life expectancy at birth from Global Education Project.

Monday, March 08, 2010

The toughest case

Taking antiretroviral (ARV) medications for HIV makes a good test case for the problem of medication adherence in general.

Digression alert: We stopped saying "compliance" and started saying "adherence" because we didn't want to sound paternalistic. But even the term "adherence" reflects some underlying assumptions that we might do better to reveal and transcend, at least for our beginning explorations. It implies that there is a right way to do things, the physicians' way, and that our goal is to get people to walk the straight and narrow, just as we expect them to adhere to law and custom. So let's try to be more neutral and say "medication taking practice" instead.

Okay, that's out of the way. ARVs are very effective in preventing the progress of HIV disease, but doctors find the evidence to be pretty clear that it's important to take them very consistently, on schedule, until death do you part from your prescription. Let me do my best to explain why.

Human Immunodeficiency Virus, HIV, is a retrovirus. The exact details of what that means aren't really essential to this story but I'll give you the basics anyway because I think it's easier to understand an explanation that is largely complete. As I presume my readers know, genes -- the instructions for making proteins and ultimately for the operation of cells and the development of multicellular organisms -- are stored in the two-stranded chemical DNA. One strand contains the actual instructions, and the other is a template for making new copies when the cell reproduces. The instructions are carried from the DNA into the cell by a one-stranded chemical called RNA.

Viruses are little packages of genetic material that get into cells and take them over, turning them into virus factories. Viruses can't reproduce on their own, they need to hijack cells for this purpose. Most viruses consist of DNA in a protein envelope, but retroviruses consist of RNA. When the RNA gets into the cell, it tricks the cell into writing its genetic code into the cell's DNA. (When we use words like "trick" that seem to imply intention or intelligence, it's just a convenient way of talking. Viruses have neither, these are just chemical reactions.)

This viral DNA inside the cell's genome is called a "provirus." Sometimes it just sits there for a long time and the cell can go about its business unaffected. But, if the viral genes are activated, the cell turns into a virus factory, releasing viral particles (called virions) into the blood stream and eventually exploding and dying. HIV gets into cells through a receptor -- a protein channel into the cell -- called CD4+. The most important cells that have these CD4+ channels are specialized cells of the immune system called helper T-cells. When they encounter cells infected with viruses, they call in other specialized cells to kill them. The body can fight HIV infection for along time, but eventually, in most people, HIV depletes the number of CD4+ cells to the point where the immune system collapses and people can no longer fight off infections. That's called AIDS.

ARVs, unfortunately, can't cure AIDS because all they can do is stop the virus from replicating; as long as there are still cells that harbor proviruses, they can start pumping out more HIV virions if the drugs aren't around to stop them.

So imagine what happens if you take your ARV meds some of the time, but not all of the time. When you skip a dose, viruses start replicating, getting out into the blood stream, and infecting new cells. If you then take the next dose, they stop replicating again. Should be okay, right? Sadly, no. The copying process is imperfect and sometimes a copy is made with a gene mutation that confers resistance to the drug. So if you then take the drug, that copy survives, successfully replicates, and pretty soon your body is full of virus that the drug can no longer control.

By the way, folks, that's called evolution, just like Darwin explained it. And if an intelligent designer is making this happen you might want to ask him just what exactly the hell he think he's up to. But again I digress.

So to give yourself the best possible chance that won't happen, you need to suppress viral replication as much as you possibly can. That way, statistically, the chance of resistant virus emerging will be very unlikely. (If you don't take the pills at all, you are very unlikely to wind up with resistant virus because it won't be selected for. In the absence of the drugs, the mutations are disadvantageous and should not lead to an expanded population of resistant virus. However, you will get AIDS.)

So what you need to do is take every dose, on schedule, for the rest of your life. Oh sure, you can miss once in a while, it's very unlikely missing once a week or so is going to be fatal, but it's still best not to. If you do develop resistant virus, you can switch to other drugs, but the reason you didn't take those other drugs in the first place is because they are more expensive, have worse side effects, and/or are harder to take. And if you do that two or three times, you will eventually run out of options entirely.

You would think that for the sake of saving your life, you would be able to do this thing, take those pills every day, on schedule. But it is actually very hard for most people to do. Other medication taking situations may pose less extreme challenges or dangers, but people have the same sorts of problems following the prescription. I'll get into some of those in coming days.

1 comment:

C. Corax said...

When you say that the medication needs to be taken every day on schedule, is there a critical aspect to the *time* it's taken, for example: every 12 hours exactly; or no less than one hour before you eat breakfast, or some such? In other words, is there an aspect of the protocol that makes it difficult to take correctly?

I suppose that active drug users aren't the people most careful for their own well-being. I'm assuming that adherence (forgive my use of that word) is worse among that population than in, say, a middle class gay population...or am I kidding myself?