HIV-1 associated dementia: update on pathological mechanisms and therapeutic approaches

Infection with HIV-1 can induce dementia despite successful administration of life-prolonging highly active antiretroviral therapy. This review will discuss recent progress toward a better understanding of the pathogenesis and an improved design of therapies for HIV-associated neurocognitive disorders.

Highly active antiretroviral therapy prolongs the lives of HIV patients, but the incidence of HIV-associated dementia as an AIDS-defining illness has increased and the brain is now recognized as a viral sanctuary that requires additional therapeutic effort. The neuropathology of HIV infection also has changed due to improved therapy, and while more similarities with other neurodegenerative diseases are being reported, predictive biomarkers remain elusive. However, improvements of in-vivo imaging technology and progress in uncovering the molecular mechanisms of HIV disease keep providing new insights. As such it appears that a prolonged activation of the immune system by HIV eventually leads to AIDS, and several lines of evidence indicate that simultaneously neurotoxic processes and impairment of neurogenesis both contribute to the development of HIV-associated neurocognitive disorders.

The improved understanding of the interaction between HIV and its human host provides hope that adjunctive therapies to antiretroviral treatment can be developed for HIV-associated neurocognitive disorders.