What is the pathophysiology of CNS complications in HIV infection?

Updated: Apr 12, 2018
  • Author: Regina Krel, MD; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM  more...
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When immune defenses are impaired, opportunistic infections and neoplasms arise, often from reactivation of previously acquired organisms. This mechanism applies to agents such as Toxoplasma gondii and Epstein-Barr virus (EBV); the latter is strongly associated with CNS lymphoma. Other organisms, such as the JC or SV40 viruses that cause PML, may be activated directly by HIV gene products.

The likelihood of a particular neurologic syndrome correlates with the clinical stage of HIV infection as reflected by viral load, immune response, and CD4+ lymphocyte counts. This, in turn, is related to the severity of immunodeficiency and autoimmunity and to serum and tissue cytokine levels.

Entrance of HIV into the CNS occurs early in the course of infection, likely within days to weeks. In contrast to the periphery where HIV infects the CD4+ T cells, in the brain, HIV targets astrocytes and perivascular macrophages/microglial cells. Several mechanisms of entry have been proposed and likely relates to transendothelial migration of infected CD4 lymphocytes and/or migration of infected monocytes. [20, 23]

Replication of HIV in the CNS results in the stimulation of proinflammatory cytokines and neurotoxins, leading to oxidative stress. Macrophages infected with the virus can form multinucleated giant cells, a classic feature seen on pathology of HIV infection in the brain. Astrocytes act as a reservoir for the virus, which typically is dormant there unless the host cells make contact with lymphocytes or become activated by cytokines. Due to the slow turnover rate of astrocytes, this site allows the virus to reside in the brain indefinitely, thereby rendering its eradication unsuccessful thus far. [19, 20, 23]

Neurons are not directly infected with the virus and damage ensues through indirect processes such as neurotoxic proteins Tat and GP120 or through the release of proinflammatory cytokines from infected macrophages. Areas of the brain most vulnerable to damage include but are not limited to the basal ganglia, subcortical white matter, and frontal cortex. [24]

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