Despite decades of intensive basic and clinical research efforts, there is still no successful vaccine candidate against human immunodeficiency virus (HIV-1). Standard combined antiretroviral therapy (cART) has been successfully developed and has given remarkable results suppressing HIV-1 infection and transmission. However, cART cannot fully clear the virus from the infected patients. A cure for HIV-1 is highly desirable to stop both the spread of the virus in humans and disease progression in HIV-1 patients. A safe and effective cure strategy for HIV-1 infection will require appropriate animal models that properly mimic HIV-1 infection and advance HIV-1 cure research. Animal models have been a crucial tool in the drug discovery process for investigation of HIV-1 disease mainly in preclinical evaluations of antiretroviral drugs and vaccines. An ideal animal model should recapitulate the main aspects of human-specific HIV-1 infection and pathogenesis with their associated immune responses, while permitting invasive antiretroviral studies. The best humanized mouse models would allow a thorough evaluation of antiretroviral strategies that are aimed towards reducing the establishment and size of the HIV-1 reservoirs. In this review, we evaluate multiple humanized mouse models while presenting their strengths and limitations for HIV-1 research. These humanized mouse models have been tailored in recent decades and heavily employed to address specific quintessential and remaining questions of HIV-1 persistence, pathogenesis and ultimately, eradication.

HIV-1 infection, combined antiretroviral therapy (cART), humanized mouse models