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Effective therapy for HIV infected patients
Approximately 35 million people worldwide are currently infected with HIV. Due to the high mortality rate, HIV is the biggest viral killer of our times. Despite major successes in reducing morbidity and mortality, toxic side effects and the development of viral resistance remain serious problems.
Improved knowledge of drug dosage via precise measurements of drug levels will help in reducing these problems. Extracellular concentrations of antiretroviral drugs can already be measured accurately, but these correlate poorly to the concentrations inside cells where the drugs should have their effect. This project not only aims to develop measuring methods for HIV antiretrovirals, but also to develop a platform to assess all aspects of the intracellular pharmacology of antiretroviral drugs. Such a platform can be used to decrease the failure rate in drug development.In the project a method was developed that has brought down the time from blood sampling to lab results to approximately two hours, using only a small sample size. Such tools can be used to improve the current treatment of HIV infected children and adults.
Full project title: A multidisciplinary approach to monitor and select effective therapy in HIV infection
Start date: April 2007
End date: April 2011
Goal: Enabling the measurement of small amounts of intracellular antiretroviral drugs
Principal investigator: Ab Osterhaus
Project size: 3 FTE's
Partners: Erasmus Medical Center, GlaxoSmithKline, TNO, Radboud University Nijmegen Medical Center
Human Immunodeficiency Virus (HIV) infection is a condition in which the immune system gradually starts to fail. The disease is contracted by transfer of infected bodily fluids such as blood and semen. The virus infects cells of the immune and central nervous system, especially T helper cells, which play a crucial role in coordinating the immune system. Four stages can be identified. The first stage covers the first few weeks in which often only a severe flu-like syndrome is observed. In about 80% of the cases the symptoms are not severe enough in this stage to consult a doctor and therefore the diagnosis is often missed. In the second stage, which lasts for approximately ten years, there are generally few mild symptoms. Some patients may experience swollen glands. In the third stage the virus becomes stronger and more varied and the immune system is already severely damaged. As the entire immune system is affected there are no specific symptoms. In general the symptoms worsen as the immune system is further affected. Diseases and infections which normally can easily be fought now have ample opportunity to develop. The final stage is the progression from HIV to AIDS (Acquired immune deficiency syndrome), making the patient vulnerable to opportunistic infections and tumors eventually leading to death.
Roland Meesters (project T4-212)
Application of MALDI-triple quadrupole mass spectrometry for the quantification of small molecules in biomedical research
Jeroen van Kampen (project T4-212)
Mass Spectrometry to Determine Intracellular Concentrations of Antiretroviral Drugs