Eradication of HIV from the brain: reasons for pause

Recent advances in HIV research have made it possible to scientists to consider approaches to eradicate HIV infection from T cell reservoirs. These include either engineering cells that would be resistant to HIV infection of suppression of HIV replication with intensified antiretroviral therapy followed by activation of HIV reservoirs and elimination of these cells by cytotoxic immune responses. Several variations of this theme are being considered. Careful consideration needs to be given to the viral reservoirs in the brain, where it may infect cell types such as macrophages, microglia and astrocytes. The life cycle of the virus in these cells is distinct compared to that in T cells and thus the antiviral approaches may not be effective in fully suppressing viral replication. Even small amounts of viral proteins produced by these cells can be neurotoxic. And if T cells in the periphery are restored before impacting the brain reservoirs these cells may enter the brain causing a T cell mediated encephalitis. This article discusses the fundamental questions that need to be addressed with regards to the biology of the virus in the brain before successful attempts to eradicate the virus can be made.