Drug-resistant virus infection has been a major hurdle in the management of human immunodeficiency virus type 1 (HIV-1) infection. Recently, three novel antiretrovirals [raltegravir (RAL), etravirine (ETR), and darunavir (DRV)] were introduced into the market almost simultaneously, and salvage regimens containing these three antiretrovirals have been reported to exhibit strong potency against drug-resistant HIV-1 infection. However, the sustainability of such regimens remains unclear, particularly for patients infected with multidrug-resistant viruses. Here we report a case of super-multidrug-resistant HIV-1 infection which has been successfully controlled by novel combination therapy including RAL, ETR, and DRV for over 2 years, indicating that the novel combination could become an ultimate weapon against drug-resistant HIV infection and could alter the landscape of HIV salvage therapy.