HIV treatment: mechanisms of neurotoxicity and implications for targeted therapy

Chengxiang Wu,1,2 Yuanan Lu1,21Department of Microbiology, 2Department of Public Health Sciences, University of Hawai'i, Honolulu, HI, USAAbstract: The central nervous system is known to act as a unique compartment where the human immunodeficiency virus (HIV) can replicate independently from the plasma and as a sanctuary in which the virus is largely protected from the host immune system and combination antiretroviral therapy. Although combination antiretroviral therapy has dramatically decreased the rate of HIV-caused mortality and associated diseases, neurological complications are increasingly common. However, our knowledge of the complicated pathogenesis and clinical symptoms of HIV-associated neurocognitive dysfunction is limited by a lack of complete understanding of the biology of HIV and its interaction with host cells in the central nervous system. This review focuses on the mechanisms of HIV entry and replication in the central nervous system, neurotoxicity caused by viral proteins and cytokine/chemokines derived from affected host cells, their implications for targeted therapy, and advances in the development of animal models for novel therapeutics in the context of combination antiretroviral therapy regimens.Keywords: HIV, HIV-associated neurocognitive dysfunction, neurotoxin, cytokines, chemokines, animal model