Transgenic mouse models of mitochondrial toxicity associated with HIV/AIDS and antiretrovirals

Since the discovery of HIV-1 and the explosion of interest in antiretroviral therapy, there has been an increasing demand for animal models to determine the underlying mechanisms of HIV/AIDS disease progression. Additionally, the advent of nucleoside reverse transcriptase inhibitors (NRTI) and the associated side effects necessitated an approach to explore NRTI toxic mechanisms in vivo. Determining the pathophysiological effects of antiretroviral drugs (such as NRTIs) on animals became an important part of understanding the risks associated with current therapeutic approaches where mitochondrial toxicity is important. Transgenic mouse models (TG) in HIV/AIDS research are valuable tools to investigate the pathophysiology of HIV-1 infection and the effects of the antiretrovirals used to treat the infection. TGs enable investigators to control these variables experimentally. This chapter summarizes data from TG models that help unravel the individual and combined effects of HIV-1 infection and NRTI therapy on mouse physiology. Emphasis is placed on cardiac mitochondrial toxicity of NRTIs used in HIV/AIDS.