(Single) witness: Mauro Moroni Drug resistance is one of the main factors limiting the success of antiretroviral therapy. Some other factors, such as individual enzymatic pattern and immune system function, play a role in the outcome of therapy in HIV infection. Moreover, adherence to treatment could also be a pivotal factor. Thus, there is a complex network that influences patients' response and ultimately contributes to the development of drug resistance. A particular situation among HIV-infected individuals is the finding of a 'discordant' response, which means a virological failure with the maintenance of an optimal immune function. In these subjects, the mere determination of the genotypic pattern of drug resistance is not necessary. Rather, the quantification of phenotypic drug resistance together with the measurement of viral fitness and/or CD4(+) T-cell dynamics will help in defining further therapeutic strategies.