Thinking about HIV: the intersection of virus, neuroinflammation and cognitive dysfunction.

It is estimated that half of HIV-infected adults and children will present at one time during their disease course with a neurologic disorder. The neurologic sequelae of HIV infection arise as a direct result of viral replication as well as from the subsequent neuroinflammatory processes. HIV enters the CNS early in infection and resides primarily in long-lived perivascular macrophages and microglia. CNS immunosurveillance is an integral part of normal brain function. Circulating lymphocytes play a vital role in support of brain plasticity under normal and traumatic circumstances. Malfunctions of this immunologic niche can impair brain homeostasis, resulting in neural impairment. Combination therapies that lower CNS viral load and improve immune homeostasis and neuroprotection will be required to address the neuropathogenesis of HIV infection.