HIV-associated neurocognitive disorders: recent advances in pathogenesis, biomarkers, and treatment.

HIV-associated neurocognitive disorders (HAND) remain prevalent despite plasma viral suppression by antiretroviral agents. In fact, the prevalence of milder subtypes of cognitive impairment is increasing. Neuropsychologic testing remains the "gold standard" of diagnosis; however, this is time consuming and costly in a resource-poor environment. Recently developed screening tools, such as CogState and the revised HIV dementia scale, have very good sensitivity and specificity in the more severe stages of HAND. However, questions remain regarding the utility of, optimal population for, and insensitivity of tests in mild HAND. Recognition of ongoing viral persistence and the inflammatory milieu in the central nervous system (CNS) has advanced our understanding of the pathogenesis of HAND and facilitated the development of biomarkers of CNS disease. The importance of the monocyte-macrophage lineage cell and the astrocyte as viral reservoirs, HIV viral proteins, self-perpetuating CNS inflammation, and CCR5 chemokine receptor neurotropism has been identified. Whilst biomarkers demonstrate monocyte activation, inflammation, and neuronal injury, they remain limited in their clinical utility. The improved understanding of pathogenic mechanisms has led to novel approaches to the treatment of HAND; however, despite these advances, the optimal management is still undefined.