Determination of viral replication capacity and viral variation in HIV infected patients failing treatment
Thursday 17 January 2013
During the last decade potent antiretroviral drugs targeted against the viral reverse transcriptase or protease have been developed for treatment of HIV infection. Despite the use of these drugs in the context of highly active antiretroviral therapy (HAART), virological failure occurs frequently and is usually associated with the emergence of drug resistant viruses. However, the development of drug resistance may not be completely hopeless, because selection of resistant viruses may affect the fitness of the viral population and change the pathogenesis of the disease. Two viral factors contributing to the fitness of the population: the viral replication capacity and the overall degree of viral diversity are both affected in failing patients. In a pilot study (protease monotherapy) we have demonstrated that initially resistant viruses with decreased viral replication capacity are selected which is accompanied by a dramatic reduction in the diversity of the viral population (bottle necking). Upon continuous treatment compensatory mutations restoring the viral replication capacity are generated. To what extent restoration of the viral replication capacity subsequently influences changes in viral diversity remains unclear, but we have demonstrated in a small patient group that the bottle necking effect persists at least 6 months.
This study aims to investigate the fitness (replication capacity and viral variation) of the viral population after failure of HAART.
Cell culture, Viral culture, Elisa, Viral RNA/DNA isolation, PCR, real-time TaqMan PCR, Sequencing, Cloning
6 or 9 months
Dr M. Nijhuis, M.Nijhuis@umcutrecht.nl
Dr A. Wensing, A.M.J.Wensing@umcutrecht.nl
Website UMC Utrecht - Medical Microbiology