HIV CENTRAL NERVOUS SYSTEM INJURIES: PATHOGENETIC FEATURES

Abstract

SUMMARY. HIV-induced injuries of the nervous system is an almost inevitable companion of HIV infection. In 45 % of patients, neurological symptoms are its initial manifestations. Since HIV primarily affects people at a young and mature age, impairment of neurocognitive functions creates difficulties in obtaining an education, productive work and personal life of people with a positive HIV status.

Lesions of the peripheral nervous system of various degrees are recorded most often. Lesions of the nervous system can be observed at any stage of HIV infection: in the subclinical phase – in 20 % of patients, in the stage of an advanced clinical picture of the disease – in 40–50 %, in later stages – in 30–90 %. The onset of neurological disorders occurs in 10-15 % of cases and includes aseptic meningitis, peripheral neuropathy (neuritis of the facial nerve, Guillain-Barre syndrome), as well as cognitive impairment and psychosis.

The issue of pathogenesis of damage to the nervous system in HIV-infected people, interactions at the cellular level are complex and still insufficiently studied. Etiological factors of HIV-associated damage to the nervous system include the direct effect of the virus on it, opportunistic infections, tumors, cerebrovascular pathology, toxic effects of antiretroviral drugs.

Ways of overcoming the blood-brain barrier by HIV have not been fully studied and remain a subject of debate. Its penetration into infected cells, endocytosis of the virus by endotheliocytes, penetration through the intercellular gaps of the endothelium of brain vessels, transportation from the cerebrospinal fluid through the ependyma, along the course of the cranial nerves etc. are assumed. The penetration of the virus into the brain can be preceded by damage of the endothelium and destruction of the virus-impermeable hematoencephalic barrier (HEB) with the help of products circulating in the blood that are toxic for the endothelium. After that, HIV replication begins in the cells of the central nervous system (CNS), which leads to an even greater accumulation of toxic components of the virus and biologically active molecules as a result of local immune activation.

Damage of the central nervous system is not limited by productive infection of HIV-sensitive cells. Neurons are the main cells responsible for brain functions, but they can not be directly infected by the virus due to the lack of CD4 receptors on their surface. Thus, a violation of the functions of neurons comes to the fore as a result of a mediated mechanism: the neurotoxic effect of virus proteins (gp120, Tat) and products synthesized in the process of immune activation of cells (TNF-α, interleukins, glutamate, quinolic acid) on the neurons themselves and cells that provide the vital activity of neurons. The neurological complications of HIV infection can be caused not only by the retrovirus itself, but also by dysfunction of the immune system. We are talking not only about known opportunistic infections that affect the brain, but also about complex AIDS dementia caused by HIV itself, and about damage of the peripheral nervous system, in particular generalized neuropathy.