This Week's Discoveries | 8 October 2019
- Tuesday 8 October 2019
Niels Bohrweg 2
2333 CA Leiden
- De Sitterzaal
Please note that, due to the new lecture schedule, the start and end time of This Week's Discoveries have been changed.
Challenging conventional wisdom on the evolution of resistance to multi-drug HIV treatment: Lessons from data and modeling.
Pleuni Pennings (San Fransico State University)
Pleuni is an assistant professor and evolutionary biologist it the Biology department at SFSU. Most of her research currently focuses the evolution of drug resistance in HIV. She wants to understand what determines the rate of evolution of drug resistance, so that we can find ways to halt the evolution of drug resistance. She is participating in the Lorentz Center workshop Predicting Evolution that is being held from 7 Oct 2019 through 11 Oct 2019
When HIV treatments became available in late 80s, they didn't work very well. HIV treatment often led to drug resistance and treatment failure. Things improved a lot in the mid 1990s when triple-drug cocktails became available. The conventional wisdom says that drug resistance should not occur when someone is treated with three drugs. But, even though triple-drug cocktails saved many a life, they did not immediately solve the problem of drug resistance.
Re-analyzing data from clinical trials in the the 90s and 2000s, we make three surprising observations. First, we see that drug resistance evolution occurs on all triple-drug treatments. Second, we see that drug resistance evolution happens one mutation at a time, and third, we see that these mutations occur in a predictable order.
We next show that while these observations cannot be explained by the conventional model of triple-drug therapy, they can be explained by a model of HIV evolution in a compartmentalized body, with compartments such as the brain and the lymph nodes. We showed earlier that so-called "single drug compartments" with limited penetration by drugs, speed up evolution of multi-drug resistance dramatically. In addition, the compartment model predicts that drug resistance evolution happens one mutation at a time and that these mutations occur in a predictable order.
In conclusion, we see that to understand HIV drug resistance evolution on triple-drug therapies, we need to consider that the human body consists of different compartments where neither drug, nor virus can move entirely freely.
To be announced.
Liesbeth de Lange (LACDR)
Liesbeth is the Principal Investigator and professor on Predictive Pharmacology in the Division of Systems Biomedicine & Pharmacology at the LACDR. Her aim is to adequately predict human drug effects using predictive pharmacological (translational) approaches.