A growing number of antiretroviral drugs have brought substantial advancements into treatment for HIV-1 infection, reducing AIDS-related mortality and morbidity in HIV infected patients. However, antiretroviral regimens are complex, cause several side effects, pose difficulties to patients' adherence to treatment and can determine emergence of viral drug resistances, the main draw back of non-adherence to drug regimens and/or sub-optimal drug bioavailability. As a consequence, new more effective and tolerable antiretroviral agents and regimens are needed, as well as new strategies for HIVdisease management. Strategically driven clinical researches are needed to address these issues.