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Neuropathogenesis of HAND: Roles for immune activation, HIV blipping, and viral tropism #MMPMID25203638
Chen MF; Gill AJ; Kolson DL
Curr Opin HIV AIDS 2014[Nov]; 9 (6): 559-64 PMID25203638show ga
Purpose of review: To discuss why HIV-associated neurocognitive disorders (HAND) persist despite apparently effective HIV suppression by highly active antiretroviral therapy (ART). Recent findings: As many as 50% of HIV-infected individuals suffer from HAND despite ART suppression of HIV replication to apparently undetectable levels in most treated individuals. Prior to ART, HIV-associated dementia (HAD), the severest form of HAND, affected ~20% of infected individuals; HAD now affects only ~2% of ART-treated persons, while less severe HAND forms persist. Recent studies link persistent immune activation, inflammation, and viral escape/blipping in ART-treated individuals, as well as co-morbid conditions, to HIV disease progression and increased HAND risk. Despite sustained HIV suppression in most ART-treated individuals, indicated by routine plasma monitoring and occasional CSF monitoring, ?blips? of HIV replication are often detected with more frequent monitoring, thus challenging the concept of viral suppression. Although the causes of HIV blipping are unclear, CSF HIV blipping associates with neuroinflammation and, possibly, CNS injury. The current theory that macrophage-tropic HIV strains within the CNS predominate in driving HAND and these associated factors is now also challenged. Summary: Protection of the CNS by ART is incomplete, probably due to combined effects of incomplete HIV suppression, persistent immune activation, and host co-morbidity factors. Adjunctive therapies to ART are necessary for more effective protection.