Highly active antiretroviral treatment(HAART) is very effective for Japanese Human immunodeficiency virus(HIV) patients in the morbidity and mortality. But the need for salvage therapy is related to the imperfection of current antiretroviral therapy. HIV-RNA load will be detectable in approximately 40% of non-naive HIV patients who are taking triple therapy after 1 year of follow-up. Treatment failure may be related to poor adherence, resistant virus and poor pharmacological bioavailability. This article aims at describing the strategic thoughts in rapid development of pathophysiological as well as clinical and drug-related knowledge. Patient commitment, physician knowledge and an informed supportive environment are important to success in salvage therapy.