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Immunomodulatory drugs role in HIV-associated neurocognitive disorders

March 21, 2017

Inflammatory mechanisms of innate immunity known to be involved in neurodegeneration in HIV-associated neurocognitive disorders (HAND) can be modulated by agents approved in autoimmune neuroinflammation leading to reduced neurotoxicity.

About 50% of HIV infected patients have neurocognitive disorders associated with the infection. Despite being on combined antiretroviral therapy (cART), HAND has a devastating impact on patients’ quality of life. Inflammation mediated by microglia, which are activated by HIV-infected monocytes, is believed to play a role in neurotoxicity independent from viral replication.

Previous research by Dr. Andrew Chan and team has shown that microglia-derived cytokines are differentially regulated in vitro and that these cytokines are associated with markers of early neurodegeneration in cerebrospinal fluid of HIV-infected patients. Various therapeutic agents are known to affect microglial and monocyte activation in the context of autoimmune neuroinflammation.

In their new study, which was published in the Journal of Neuroinflammation, researchers investigated effects of teriflunomide and monomethylfumarate on monocyte and microglial activation and neurotoxicity. They found that modulation of innate immune functions by teriflunomide and monomethylfumarate targets neurotoxic inflammation in the context of HAND.

New treatment approaches are urgently needed as it is expected that HAND will in future pose a high socioeconomic burden due to higher life expectancy of HIV-infected patients and increase of severity of HAND over time. Further work needs to be done to provide more evidence in using autoimmune neuroinflammation agents such as teriflunomide and monomethylfumarate in combating HAND.


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