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 It can be happening with a lot of recombination, or showing clonal interference (unpublished, Kadie-Ann Williams and PSP), and sweeps can be hard or soft.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!

 

 

HIV prevention in the 21st century

A little over 700 HIV-positive men and women had sex with their HIV-negative partners 44 thousand times, without using condoms, and not a single new HIV infection was found! This result of a large European study was one of the big stories last week at the CROI meeting in Boston (Rodger, 2014, CROI). How this is possible? Well, the HIV-positive partners were taking modern antiretroviral drugs and they had almost no virus in their body that could be transmitted to their partners.

HIV drugs

In the last 30 years more than 20 different antiretrovirals were developed to treat HIV and thanks to those drugs HIV-positive people can now live long and healthy lives. The modern antiretrovirals are always taken as cocktails of multiple drugs, but nowadays these cocktails are often available as one-pill-per-day formulas and their side effects are really quite mild.

Treatment is also prevention

Until recently, most HIV-positive people waited quite a while before starting treatment. Guidelines suggested to wait until the immune system started to give up (as indicated by a CD4 count of less than 400). However, this is changing as it is becoming clear that treatment not only keeps the immune system of the HIV-positive person healthy, it also prevents transmission to his or her HIV-negative partners. A classic case of two birds with one stone!

More effective than condoms

It turns out that HIV treatment is much more effective in preventing transmission than condoms are. Of course, condoms work, when they are used. But people are much better at taking their HIV medication every night than they are at consistently using condoms. This shouldn’t come as a surprise. Many women take the birth control pill every night to prevent pregnancy. If everyone would use condoms all the time, the pill would be unnecessary for most women.

PrEP

For a long time, doctors hesitated to tell people that HIV treatment prevents transmission, because they were afraid that their patients would stop using condoms all together. The same fear plays a role with another use of antiretrovirals. Last year the FDA approved Truvada (a simple cocktail of just two antiretrovirals) for use by HIV-negative people to reduce their risk of infection. This is called “Pre-exposure prophylaxis”, or PrEP. PrEP works quite well. A large study amongst gay men in several different countries found that Truvada roughly halved the risk of infection (Grant, NEJM, 2010). Amongst the men who toke the pills 7 days a week, the risk was reduced by 99% (Anderson, Science Transl. Med., 2012)!

Truvada is a pill that consists of two antiretrovirals (tenofovir and emtricitabine) and is used for HIV prevention as well as HIV treatment (the latter case always in combination with a third drug).

No drugs for healthy people?

99% efficacy, that sounds like a real breakthrough, doesn’t is? You’d think that gay men in San Francisco and other people at risk would start using Truvada en masse. However, this is not the case. The idea of HIV-negative people taking HIV drugs is very controversial (see this NYT article). First of all because doctors don’t like to prescribe drugs to healthy people. This is understandable, but I think that these same doctors wouldn’t hesitate to prescribe the birth-control pill to healthy women. Sometimes prevention is worth the side-effects.

Risk compensation

A second reason why PrEP is controversial is because of the fear of so called “risk compensation”, that is, the fear that people who take the pills feel safe and reduce their use of condoms so much , that in the end they are at higher risk of infection than without the pills. Regarding this point, there is some good news though: A recent paper (Marcus, PLoS One, 2013) showed that risk compensation did not occur amongst people in a large PrEP study, even amongst those who believed that the drugs were working very well to protect them against HIV infection. It seems to me that the time is ripe for large scale use of PrEP. Maybe one day, taking Truvada to prevent HIV becomes as normal as taking the birth control pill.

Even better

What would be really useful for many women in this world is a pill that combines HIV prevention and birth control in one! I hope someone is working on this.

Note: this blogpost is based on a column I wrote for Bionieuws, the newspaper of the Dutch Biology Institute.