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Bayjanov Allabergan Kadirovich, chief doctor of Samarkand Regional Clinical Infectious Disease Hospital, Samarkand Utegenova Sohiba Komilovna, The Research Institute of Virology the Ministry of Health Tashkent, Uzbekistan E-mail: evovision@bk.ru
PATHOGENETIC ASPECTS OF NEUROCOGNITIVE DISORDERS IN HIV-INFECTED INDIVIDUALS
Abstract: Insufficiency of suppression of viral load in liquor during therapy with protease inhibitors, characterized by moderate penetration into the Central nervous system, indicate that the main role is played by the degree of penetration into the cerebrospinal fluid and substance.
Keyword. CSF, brain, viral load.
HIV remains one of the major global health challenges: it has claimed more than 35 million lives to date. In 2016, 1.0 million people worldwide died from HIV-related causes. At the end of 2016, there were approximately 36.7 million people with HIV in the world, and 1.8 million people acquired HIV in 2016 [3]. 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 the developed clinical picture of the disease - in 40-50%, in later stages - in 30-90% [14].
The aim of research. Based on the analysis of scientific literature data on the pathophysiological mechanisms of formation of HIV-associated neurocognitive disorders to identify the factors that determine their severity of violations, to search for optimal methods of their early diagnosis
It is known that the result of immune activation is the increasing loss of CD4 + lymphocytes and the disruption of the HIV-specific immune response. However, persistent activation of immunity also contributes to the emergence of other diseases. In particular, cardiovascular complications, non-alcoholic steatohepatitis, renal dysfunction, osteoporosis, insulin resistance, metabolic syndrome, and HIV-associated neurocognitive impairment [13].
The cause of HIV-associated neurocognitive disorder (HAND) is damage to the central nervous system by the action of the immunodeficiency virus. If untreated, the virus replicates intensively in macrophages and microglial cells of the brain substance. No reliable signs of direct infection of neurons have been identified, however, immunopathological changes lead to functional and structural disorders in these cells. The central nervous system is a relatively independent of the hematolymphatic system of the body, which creates conditions for viral replication and the formation of quasi-species. In the HAND classification, the following degrees of severity are distinguished: "asymptomatic neurocognitive disorder"
(ANI), "mild neurocognitive disorder" (MND) and "HIV-associated dementia" (HAD). With an increase in the life span of patients, the prevalence of HAND reaches 20-50% [19].
According to the latest literature, the frequency of detection of neurocognitive impairment is from one-third to one-half of HIV-positive patients in a large population. With the expansion of ART, the prevalence of severe cases decreases, but mild cases increase [11; 12].
The incidence of mild or moderate neurocognitive impairment is higher today than in the period prior to highly active antiretroviral therapy (HAART). The presence of HAND is associated with a shortened lifespan [22].
Before HAART, this pathology was observed in 15-20% of patients. After the introduction of HAART, the frequency has decreased, but to a lesser extent than is typical for other manifestations of AIDS [5].
While the main method of treating HAND in naive patients, of course, is HAART, data on the severity and duration of its effect are unconfirmed. Results from several studies suggest that chronic, progressive, and sometimes intermittent cognitive impairments develop in HIV-infected patients with suppression of plasma viraemia [1; 18].
In the course of longitudinal studies assessing the course of neurocognitive disorder in patients with asymptomatic HIV infection for five years, cognitive abilities were predominantly stable. Earlier initiation of antiretroviral therapy is associated with a decrease in the frequency of HAND [2].
In patients with initially low CD4 levels, several years after the initiation of HAART, cognitive performance was worse than that of HIV-negative, but with a tendency to improve. Severe HIV-associated dementia in patients receiving HAART is rare today. Even in HIV-infected individuals with persistent and stable suppression of viral replication, subjective complaints about mental decline and objective impairment of neu-
PATHOGENETIC ASPECTS OF NEUROCOGNITIVE DISORDERS IN HIV-INFECTED INDIVIDUALS
ropsychiatric functions, including HIV-associated dementia, are often recorded [20].
On the contrary, in everyday clinical practice, lungs have become more frequent, but clinically significant in relation to work activity are neurocognitive impairments; in addition, in recent years, these manifestations have developed at earlier stages of HIV-induced immunosuppression [5].
Before HAART, the viral load in the cerebrospinal fluid and blood plasma, as well as the current level of CD4, was considered the main predictor of HAND development. Currently, this relationship is denied. Recent research has established the following risk factors for cognitive impairment: minimal CD4, severe immunosuppression or AIDS, prolonged length of HIV infection, low level of education, old age, and elevated plasma concentrations of TNF-a and MCP-1 [7].
The development and persistence of manifestations of HAND, even against the background of HAART, is probably due to a chronic increase in immune activation indices in the CNS [6; 8; 14], which to some extent leads to a "disconnection" of the processes occurring in the brain system.
In modern works on histopathology, there are data on some patients who were diagnosed with HAND several months before death, but after death no signs of active viral replication were detected in the brain substance, only signs of immune activation and neurodegeneration were detected [4; 9].
In patients with marked suppression of virus replication at the system level, severe manifestations of HIV-associated dementia rarely develop, and a high viral load can be detected in the CSF [16; 21].
Histopathological examination in these cases revealed clusters of lymphocyte CD8 +, located perivascular and in the parenchyma, sometimes in close proximity to neurons. Sometimes patients around the patient notice the symptoms of the disease faster than the patients themselves. Typical complaints include slower reactions, impaired memory, concentration and motivation, mild depressive symptoms and a flattening of affective reactions. The correlation between subjective complaints and objective neuropsychological disorders is poorly expressed [3].
Unambiguous disturbances of activity, focal neurological symptoms and signs of lateralization (hemiparesis, apha-
sia, and others) or meningism are not typical for HAND, as are mental symptoms without concomitant cognitive-motor disorders. HAND is also rarely combined with psychotic symptoms. The diagnosis of HAND is made based on clinical, neuropsychological and instrumental data. Only the results of instrumental studies for the diagnosis of HAND are not enough. From a clinical point of view, cognitive impairment comes to the fore. Psychopathological and, moreover, motor disorders in the initial stages may be absent or be isolated, but there is always severe dementia (stage HAD). There are simple screening tests designed to assess cognitive impairment on the scale of HIV-associated dementia [23].
To some extent, this is the generalized MOCA test, which is also used in Alzheimer's disease [17].
However, the gold standard for diagnosis is a general neuropsychological study, which includes an assessment of cognitive function in at least five domains (speech, attention / working memory, abstract thinking / executive function, learning ability / response to a request, speed of information processing, motor skills).
In 2013, an international consensus was published on the subject of screening, monitoring, diagnosis and treatment of HAND [15].
The goal of etiotropic therapy for HAND is to suppress viral replication in the CNS. In addition, despite the possibility of isolated replication in the central nervous system, an-tiretroviral therapy in most cases leads to a rapid decrease in the viral load in the cerebrospinal fluid. In parallel, during the first 3-9 months, there is an improvement in neurocognitive indicators. Reports of insufficient suppression of viral load in the cerebrospinal fluid during therapy with protease inhibitors characterized by moderate penetration into the CNS (10) indicate that the degree of penetration into the cerebrospinal fluid and brain matter plays a major role. The question of which antiretroviral drugs and in which combinations it is optimal to prescribe remains unspecified.
The above dictates the feasibility of conducting a study on the pathogenetic mechanisms of development and optimization of the diagnosis and treatment of neurocognitive disorders in HIV-infected individuals.
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