‘HIV Head Mortgage’ by Chris Keegan
I was reading through this excellent Frontline story on AIDS and I finally understand what the drug cocktail business is. What’s remarkable is that, 25 years in, HIV is effectively treatable. The combination of drugs prevents it from replicating for up to 10 years or more, and people that take their consistent dose register almost zero retroviral count. They basically have their lives back, for a while. What is more insidious (and interesting) is that HIV is the fastest evolving thing I’ve ever seen. This means that it eventually outmutates the drug cocktail. What’s interesting is that HIV replicates literally billions of times per day. That means that it goes through generations in a matter of seconds and can overcome a single drug in just a few iterations. That’s why people are given multiple overlapping drugs at once. But HIV is so adaptive that it eventually adapts to even this. It is the most vicious and obvious example of evolution I’ve ever seen.
Evolution, from what little I’ve studied, is the ‘process by which novel heritable traits arise in populations and are passed from generation to generation; over time, those traits that help an organism reproduce in greater numbers than its peers gradually gain dominance in a population’ (Wikipedia). It is basically a process of communication between species and environment as the species learns how (and if) it can exist in the midst of change. Normally it moves too slow to observe but the replication of HIV is so fast that you can see it happening in real time, with very real effects.
The ‘mechanism’ by which evolution discovers novel traits isn’t intelligence of any sort, but pur error. DNA simply gets mixed (sexually) or mistranscribed into novel forms. The former (sexual selection) leads to more useful traits because the ability to reproduce actually has some relation to your evolutionary fitness, unlike the randomness of mistranscription. HIV, however, doesn’t reproduce sexually. Rather, it has an extremely error prone transcription process and the sheer tenacity of its replication means that it can simply use brute force to find a way around the immune system and drugs.
HIV is composed of RNA, not DNA. RNA is, loosely, the carbon copy of DNA, used for sending messages to make proteins and stuff. It is more unstable, meaning that more errors can be introduced during replication.
Replication cycle of HIV
The image above kinda shows it, and this Hopkins interactive goes into detail. I left sex education before these drugs were widely deployed and never really knew. Very broadly, there are three sets of puzzle pieces that can gum up the work of HIV. The one thing I liked about the limited genetics I studied was how everything was about shapes, it was very visual (though not taught that way). Basically, you can stop HIV from 1) reading the protein (left) 2) writing the enzyme (right) or 3) fusing with the CD4 immune cell at all (nubs on the side). Each of those interactions are governed by chemical ‘keys’ that fit into place. The drug cocktail flushes the immune system with a set of keys that gum up each part of the process. What interesting is that if you use just one drug, the HIV will almost immediately produce a plethora of variants, one of which will have adapted to replicate without the keyhole that was gummed up. Very quickly that generation will take over the environment and that drug won’t work anymore. It’s standard evolution, but it happens over days rather than millenia. That’s why multiple drugs are needed, because the probability of a random mutation overcoming all the different challenges at once is very low. However, if someone skips a dose then the HIV becomes immediately more virulent. The interactive is worth watching, it’s kinda scary and fascinating at the same time.
What is amazing is that the drug cocktail does generally work. With significant side effects that sorta fade, but AIDS is no longer a death sentence as the drugs can make HIV disappear below detectable levels for a long time. This means that people can function in developed countries, but there is still a huge need in Africa, and timebombs in India and China. Despite not being a cure, it is a huge step forward for a lot of people, and pretty amazing science. The Frontline Report is great, I spent most of Sunday reading it.