Lytvyn K. HIV-associated infectious lesions of the brain: clinical and immunological, morphological characteristics, diagnosis and treatment

The dissertation is devoted to the study of demographic, clinical and immunological features of HIV-associated infectious diseases of the brain, improvement of diagnostics, prediction of the course, individualization of approaches to prevention and treatment. The study involved 701 people, of whom 674 were HIV positive. 482 patients were diagnosed with HIV-associated diseases of the central nervous system (451 patients were on inpatient treatment, 31 patients underwent outpatient monitoring in the Dnipropetrovsk regional and city AIDS centers). To study the cognitive status, 95 patients of an outpatient group with HIV without any neurological diseases were involved. The control group comprised 124 people, of which 27 were HIV-negative. HIV-associated CNS lesions in hospitalized patients were characterized by high mortality (42.4%), a higher risk of death in males (p <0.01), and late detection of HIV status (p <0.001); absence of ART (OR = 6.36; p <0.001); at a CD4 + level less than 50 cells / μl (OR = 2.23; p <0.001) and high viral load (VL) HIV RNA copies / ml in blood (OR = 1.76; p <0.001). Among the HIV-associated lesions of the brain, infectious opportunistic diseases were dominating: tuberculosis (TB) (37.3%), cerebral toxoplasmosis (29.9%), mycosis of the central nervous system (17.1%), EBV-encephalitis (10.6%). The highest risk of lethal outcome was associated with CNS diseases caused by TB infection (OR = 8.64; p <0.001). Patients older than 50 years (11.8% of all patients with HIV-associated CNS diseases) had such features as the tendency to a higher mortality rate – 50.9% vs. 41.2% in the younger age group (p = 0.186 FET ); late detection of HIV (56.6% vs. 41.5%; p <0.05); the prevalence of the sexually transmitted infection (63.9% vs. 40.4%; p <0.05); lower coverage of ART (22.6% vs. 41.7%; p <0.01); higher level of VL: median HIV RNA – log 5.72 vs. 4.90 copies / ml; p<0.05; 3.99 times higher chances of cognitive impairment (p <0.001) and a higher frequency of these disturbances in patients receiving ART (58.3% vs. 25.3%; p <0.05); a 3.78-fold higher risk for PML and 2.2% for EBV-encephalitis (p <0.05). With involvement of the central nervous system, an unfavorable prognosis of the disease was associated with decreased consciousness (OR = 6.11; p <0.001), meningeal symptoms (OR = 3.92; p <0,001), a rise in temperature ≥ 38.0 ° C (OR = 2.92; p <0.001) and seizures (OR = 2.35; p <0.05).Based on the studied mechanisms and consequences of nervous system damage, mathematical models were created which allowed with high precision and specificity evaluate prognosis of brain involvement and risk of lethal outcome of the disease in HIV-infected patients, using the combination of above-mentioned markers.