Systems pharmacology of HIV inhibitors

The human immunodeficiency virus (HIV) is still on the advance, 25 years after its discovery. Although the virus can be suppressed by antiviral treatment, it cannot be cured. The spread of drug resistant virus is a major health concern, which necessitates the continuous development of new and expensive drugs.

 

We are particularly interested in the mechanisms of drug resistance in HIV: Which circumstances allow the virus to overcome treatment-induced selective pressure, what are the consequences for the virus, and how can these mechanisms be detected in time and be counteracted?

 

In this project, we are developing mathematical models and methods, which integrate molecular biology data with pharmacokinetic – and evolutionary data in order to derive a holistic picture of the processes, which drive the development of drug resistance in HIV.

 

The project is funded by the German Ministry of Education and Research (BMBF).

Selected Publications

  • von Kleist M, Menz S, Huisinga W.(2010), Drug-class specific impact of antivirals on the reproductive capacity of HIV. PLoS Comput Biol., 6(3):e1000720

 

  • von Kleist M, Huisinga W. (2009), Pharmacokinetic-pharmacodynamic relationship of NRTIs and its connection to viral escape: an example based on zidovudine. Eur J Pharm Sci.36(4-5):532-43

  • von Kleist, M. and Metzner, P. and Marquit, R. and Schütte, Ch. (2011) Polymerase inhibition by nucleoside analogs: Cellularand kinetic parameters of efficacy, susceptibility and resistance selection. Plos Pathogens (Submitted)

  • von Kleist, M. and Menz, S. and Stocker, H. and Arasteh, K. and Huisinga, W. and Schütte, Ch. (2011) HIV Quasispecies Dynamics during Pro-active Treatment Switching: Impact on Multi-Drug Resistance and Resistance Archiving in Latent Reservoirs. Plos One, 6 (3). e18204.

Head:

Max von Kleist

Project researchers

Max von Kleist, Stephan Menz, Christof Schuette