New plans and new HIV stories

I love making plans and I love the beginning of the new year and the new semester. I actually think that the yearly rhythm of semesters and breaks is a huge benefit of being in academia.

Today I spent some time thinking about the writing I plan to do in the coming semester and the talks I will be giving in the near future. The first talk that’s coming up is an invited talk at Stanford. I am very honored to be an invited speaker at the CEHG symposium alongside Anne Stone (ASU) and Graham Coop (UC Davis). I want to try and use the opportunity of the talk to think about what stories I want to tell and I plan to write the story up for publication in addition to talking about it at Stanford.

So what are the stories I want to tell? There are many! But here are some thoughts:

“The evolution of HIV evolution.”

Recently I’ve given seminars in which the overarching storyline was “The evolution of HIV evolution.” I focused on the evolution of drug resistance within patients and explained how drug resistance evolution used to be very fast, but became slower over time. When people were treated with a single drug (AZT) in the late 80s and early 90s, the virus would evolve drug resistance very quickly and the treatment would quickly become useless. Freddy Mercury probably died because of a very fast evolving virus. Over time, treatments improved (using combinations of drugs and using better drugs) such that it became harder for the virus to evolve and nowadays, drug resistance evolution is so slow in patients on treatment, that it is no longer a big worry, and people can stay on the same drugs for many years.

A slide from a talk I gave at SMBE and ESEB in the summer of 2017.

“HIV does it all”

Here is another storyline. Any field in science needs some systems that are looked at in detail. In evolutionary genetics, these systems are fruitflies, yeast, humans, mice etc. HIV is a great system as well in part because we know so much about it and data is abundant. One of the things we have learned in recent years, thanks to work by people like Richard Neher and Kathryna Lythgoe, is that HIV evolution can surprise us again and again. For example, HIV evolution, even in absence of drugs, can be fast within patients and slow at the epidemic level. It can be happening with a lot of recombination, or showing clonal interference (unpublished, Kadie-Ann Williams and PSP), and sweeps can be hard or soft. Within host populations can be panmictic or structured. So if everything can happen, how can we make sense of this all?

“Drugs to prevent HIV”

I like the story of how drugs were and are used to prevent HIV infection. In the 90s and well into the 2000s, drugs were used to prevent mother-to-child-transmission of the virus during child birth. In fact, this was one of the big successes in the world of HIV before treatment was really working to keep infected people alive. Nowadays, drugs are available for HIV-negative people who are at increased risk of HIV infection. Pre-exposure-prophylaxis (Prep, marketed as Truvada) is probably contributing to the shrinking of the HIV epidemic in San Francisco as many of the HIV-negative gay men in the city are taking Prep. When drugs were used to save babies, they were uncontroversial, but when they are used to save gay men, they continue to be controversial and there are many places where Prep is not available (for example, in my home country, The Netherlands).

How is this story linked to evolutionary genetics? When someone is taking drugs to prevent HIV, but they end up getting infected anyways, there may be a high risk of drug resistance evolution (this happened in the babies, in their already infected mothers, and it is happening occasionally in Prep users). Also, at an epidemic level, if a large part of the population is on Prep, this may lead to sub-epidemics of drug-resistant viral strains. There is some interesting modeling work by Sally Blower on these questions.

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OK, that’s enough brainstorming for today. I’ll develop one of these stories into a presentation for CEHG and for an article to be published somewhere. If you have any questions or suggestions, let me know!