"HIV-1 infects principally T4 lymphocytes. HIV infection has been reported to affect over 40 million people world wide, with 4 new million people infected each year.Regarding the effort put to stop HIV infection, there is no effective solution. During the last years, several studies have been done to find out more about the existence of intra-patient population structure (different viral population in different patient organs). In our previously reports we performed an in silico meta-analysis. The results highlight the detection of organ compartmentalization in proviral sequences of pol, gag and env HIV proteins. Those viruses found in nervous system (NS) and liver are significantly different from those found in the rest of the body organs, these differences have been associated to a different selection constraints acting on the virus in the different organs. This can be the cause of antiviral therapy failure.The binding of viral peptides with the Major Histocompatibility Complex and the recognition form the immune system T-Cells, are necessary to finish with viral infection in vertebrates. For this reason there is a coevlutionary history between viral particles proteins and cell receptors.The main aim of the project is the combination of in silico (principally) and in vitro/in vivo (when this is possible) approaches to be able to understand (i) evolution of the virus inside of the body, (ii) selection constraints forcing the differential evolution of the virus, (iii) understand and predict protein-protein interactions (between cell receptors and Env viral protein) performing molecular coevolutionary analyses. The information obtained from the project has it relevance at clinic ad economical level. If we are able to explain how virus evolves, how new resistant viruses appear, and how virus interact with cell receptors, we can help to fight against HIV."