Nonhuman Primates and Humanized Mice for Studies of HIV-1 Integrase Inhibitors: A Review

Abstract

Since the discovery of the first inhibitors of HIV replication, drug resistance has been a major problem in HIV therapy, due, in part, to the high mutation rate of HIV. Therefore, the development of a predictive animal model is important to identify impending resistance mutations and to possibly inform treatment decisions. Significant advances have been made possible through use of nonhuman primates infected by SIV, SHIV, and stHIV-1, and use of humanized mouse models of HIV-1 infections. In this review, we describe some of the findings from animal models used for the preclinical testing of integrase strand transfer inhibitors as well as other antiretroviral drugs. These models have led to important findings about the potential role of integrase strand transfer inhibitors in both the prevention and treatment of HIV-1 infection.

Keywords

• nonhuman primates
• integrase strand transfer inhibitors
• integrase
• drug resistance mutations
• simian immunodeficiency virus (SIV)
• simian-human immunodeficiency virus (SHIV)
• simian-tropic human immunodeficiency virus (stHIV-1)