Lead


Lay summary
HIV drug resistance is a major obstacle in the fight against HIV-1. New technologies allow to detect minority quasispecies of drug resistant viruses. In this project we will investigate the impact of virus diversity and quasispecies dynamics on selection, persistence, and transmission of drug-resistant viruses. Firstly, we will determine to what extent transmission of drug-resistant viruses is underestimated using conventional direct sequencing. Secondly, we will determine what impact the presence of minority quasispecies of drug-resistant HIV-1 do have on subsequent antiretroviral treatment responses. Thirdly, we aim at identifying cellular populations in which residual repolication of HIV-1 may occur despite suppressive ART and will investigate the possible impact of a cellular host factor (ABPOBEC-3G) on HIV-1 diversity, and potentially on the emergence of HIV-1 drug resistant quasispecies. The combination of new technologies such as allele-specific PCR and ultradeep sequencing with carefully defined patient collectives from the Zurich Primary HIV infection Study and the Swiss HIV Cohort Study will allow us to generate meaningful results. In conclusion, this study will guide us to further optimize antiretroviral long-term treatment strategies and will give us insight into better understanding the emergence of viral diversity, one of the key features of HIV-1 infection.