LECTURE
This article will review the main characteristics of West Nile fever virus (WNV), including its spread, pathogenesis, clinical manifestations, and long-term effects on human health. The main focus will be on analyzing the interaction of the virus with various body systems, the mechanisms of its penetration into tissues, and the characteristics of the immune response to infection. The study covers the molecular aspects of pathogenesis, the genetic structure of the virus, the dynamics of its spread, as well as diagnostic, preventive and treatment methods. Particular importance is attached to the analysis of the characteristics of various virus strains, their evolution and geographical distribution. This will allow us to identify trends in the development of infection and develop strategic approaches to its prevention. The study of the mechanisms of the virus’s effects on the nervous, visual and cardiovascular systems, as well as the identification of factors influencing the development of complications, are key aspects of this work. The article is intended for specialists in the field of medicine, including students, residents, postgraduates of medical schools and doctors of various medical specialties.
Hepatitis D (HD) is a severe infectious liver disease caused by a defective RNA virus, the hepatitis D virus (HDV), whose replication is obligately dependent on the hepatitis B virus (HBV), which provides envelope proteins. The disease is associated with a high risk of rapid progression to cirrhosis and hepatocellular carcinoma. The aim of this lecture is to provide a comprehensive overview of current data on the epidemiology, pathogenesis, diagnosis, and treatment approaches for hepatitis D, as well as to highlight key unresolved questions in this field. The lecture summarizes key aspects of the disease. It examines the biology of HDV and its obligate dependence on HBV, which defines a unique pathogenesis involving direct cytopathic and immune-mediated damage. Current epidemiological data are presented, indicating a significant and often hidden global disease burden. Diagnostic algorithms, their capabilities and limitations related to viral variability, are described. The evolution of therapy from interferons to novel targeted drugs is highlighted, along with the role and limitations of HBV vaccination as the primary preventive measure. The lecture emphasizes that effective control of HD requires a comprehensive approach combining the development of specific antiviral therapy, the expansion of diagnostic screening, and the steadfast strengthening of global HBV vaccination programs. Thus, the key challenge lies in the need to combine the global expansion of simple and effective prevention with the development of fundamentally new, more effective treatment and diagnostic methods for millions of already infected patients.
ORIGINAL STUDIES
From 2018 to 2024, the Russian Federation witnessed an increase in the number of young people with perinatally acquired HIV (PHIV) who reached the age of 18 years and transitioned to adult care. It is known that young individuals with PHIV have a duration of HIV infection equal to their age (more than 18 years), with delayed or late initiation of antiretroviral therapy (ART), often in the setting of advanced disease stages. In addition to the direct damaging effect of HIV and the associated chronic inflammation, the toxic effects of certain antiretroviral drugs (ARVs) are well documented; their use has been accompanied by a significant number of adverse events and side effects, which have led to the need for ART regimen changes.
The aim. To analyze the dynamics of HIV infection treatment in young people with perinatally acquired HIV infection from the time of ART initiation up to the present.
Materials and methods. A retrospective-prospective study using consecutive sampling included 105 adult patients with PHIV, born between 1999 and 2005, who had been under dispensary follow-up at the St. Petersburg AIDS Center (AC) since childhood. An analysis of epidemiological, clinical, and laboratory parameters was performed for the period from birth to 2025 inclusive. Retrospectively, the following were assessed: age at HIV diagnosis and at treatment initiation, ART regimens, frequency of adverse events (AEs) and side effects (SEs) of ARVs, and reasons for switching therapy regimens. Prospectively (2019–2025), ART regimens, virological, immunological, and clinical efficacy of ART after patients’ transition to adult care, as well as treatment adherence, were analyzed. Statistical analysis of the obtained clinical data was performed using STATISTICA for Windows (version 12).
Results and discussion. At the time of HIV diagnosis, the mean age of children was 2.6±4.3 years (min — first days of life, max — 17.4 years); the age at ART initiation was 7.2±4.5 years; the median interval between diagnosis and treatment start was 4.6 years. At treatment initiation, two-thirds of patients had immunodeficiency of varying severity. Initial ART regimens included protease inhibitors (PIs) in 95.2% of cases; they were highly effective, but required substitution in 78% of patients, mainly due to adverse events (54.3%), among which hematologic disorders, dyslipidemia, and peripheral neuropathy predominated. By the time of transition to adult care, 85.7% of patients were receiving ART as fixed-dose combinations (FDCs). Nevertheless, 16.2% of patients (n=17) discontinued treatment. Among those remaining under follow-up (n=88), 25.6% (n=21) had immunodeficiency three years after transition, and 13 (15.8%) individuals had detectable viral load.
Conclusion. Thus, the cohort of adult patients with PHIV is characterized by a long disease duration, late initiation of antiretroviral therapy, a high incidence of adverse events and side effects associated with highly toxic antiretroviral drugs, and multiple treatment regimen switches. Fatigue resulting from lifelong medication intake was accompanied by reduced treatment adherence after transition to the adult AIDS Center department, leading to the loss of a significant proportion of patients from follow-up. Optimization of ART by switching children to new drugs in the form of fixed-dose combinations with a low toxicity profile was the main reason for regimen changes starting from the third line of therapy, and contributed to retaining the majority of adolescents — and subsequently adult PHIV patients — on treatment. As a result of high treatment adherence among patients who remained under the care of AC specialists, no clinical manifestations of HIV disease progression were observed.
The aim: to assess the mental, psychological, and social characteristics of men with risky behavior in a cohort of people living with HIV (PLWH).
Materials and methods. 114 men infected with the human immunodeficiency virus (HIV) via male-to-male sexual contact were examined. The clinical-anamnestic method (medical record review), laboratory tests, and an experimental-psychological method in the form of questionnaires were used.
Results and discussion. According to our study, 76% of the men had higher, unfinished higher, or vocational/secondary education, and 90% were actively employed. The mean duration of follow-up at the Center for the Prevention and Control of AIDS and Infectious Diseases (AIDS Center) was 5.2±4.5 years. Virological success of antiretroviral therapy (ART) (HIV RNA<40 copies/mL) was achieved in 81% of patients. Current or past hepatitis C virus infection was detected in 23% of the men. A history of treatment for sexually transmitted infections (STIs) was reported by 78% of patients, of whom 61% had ever had various forms of syphilis. Ninety-three percent of respondents were aware of the possibility of post-exposure prophylaxis for STIs, but only 29% had used it. Group sexual practices were reported by 61% of the men, and 22% had experience of commercial sex. Sixty-eight percent of patients had been seen by a psychiatrist at the AIDS Center. Among psychiatric diagnoses, the most common were substance dependence syndromes (27%), neurotic and stress-related disorders (22%), and organic mental disorders (20%). Use of psychoactive substances (PAS) was acknowledged by 38% of the men; of these, almost half (41%) used synthetic cathinones for chemsex. At the time of the study, 20% of respondents were actively drug-dependent. According to the personality structure assessment (Mini‑SMIL), MSM predominantly demonstrated optimism (3.3±1.3), femininity (2.6±1.0), and impulsivity (2.6±1.0). Patients with casual sexual contacts less frequently exhibited schizoid personality traits (Mini‑SMIL) (p=0.02), less frequently reported emotional lability (p=0.03), more often had elevated mood (p=0.006), and more often used psychoactive substances (p=0.01).
Conclusion. HIV-infected MSM demonstrate low psychological resilience and require the development and implementation of comprehensive prevention and support programs.
The аim: To analyze clinical, laboratory, and socio-demographic characteristics of men with HIV infection at stage 4B depending on the timing of antiretroviral therapy (ART) initiation.
Materials and methods. A retrospective study of 120 men with stage 4B HIV infection undergoing follow-up at the Leningrad Region AIDS Center was conducted in 2024–2025. Clinical, laboratory, and sociodemographic data from primary medical records were assessed and analyzed. Microsoft Excel 2010 and StatTech v. 4.1, the Kruskal–Wallis test, Pearson’s χ2 test, and Fisher’s exact test were used for statistical processing and mathematical analysis of the data. The Bonferroni correction was used for multiple pairwise comparisons. Differences were considered statistically significant at p<0.05.
Results and discussion. All patients received antiretroviral therapy (ART); however, most patients had progressive disease, and viral load suppression (<50 copies/mL) was achieved in only 28.3% of cases. Patients were divided into three groups comparable in age and disease stage: Group 1 (n=40; 33.3%) — ART initiated within the first year after diagnosis; Group 2 (n=40; 33.3%) — ART initiation delayed for 1–10 years; Group 3 (n=40; 33.3%) — ART initiated more than 10 years after diagnosis. As the delay before ART initiation increased, the proportion of men living with family decreased from 72.5% in Group 1 to 37.5% in Group 3, as did the proportion of patients with permanent employment (80% and 35%, respectively). At the same time, the proportion of patients with a history of incarceration increased (35%, 45%, and 55%, respectively), as did the prevalence of injectable psychoactive substance use (27.5%, 60%, and 87.5%, respectively). Mean CD4 lymphocyte counts remained low in all groups but were higher in Groups 1 and 2 compared with Group 3 (234.5 cells/mL, 176.4 cells/mL, and 112.6 cells/mL, respectively).
Secondary conditions included pneumocystis pneumonia (PCP), candidal esophagitis, cytomegalovirus (CMV) infection, HIV encephalopathy, cerebral toxoplasmosis, cryptococcal meningitis, progressive multifocal leukoencephalopathy (PML), tuberculosis, mycobacteriosis, and malignant neoplasms. A trend toward an increasing proportion of patients with three secondary conditions from Group 1 to Group 3 was observed (20%, 25%, and 40%, respectively), while the proportion of patients with only one secondary condition decreased (47.5%, 37.5%, and 25%, respectively).
Conclusion. Late initiation of ART is associated with less favorable clinical and social characteristics of patients (low CD4 count, high incidence of secondary diseases, injection drug use, social instability, and history of incarceration). A limitation of the study is its retrospective design, which precludes assessing the causal relationship between the factors studied and disease progression.
The aim: to analyze the characteristics of HIV infection and the structure of comorbid diseases in women of childbearing age.
Materials and methods. A total of 100 women of childbearing age were studied at the Republican Clinical Infectious Diseases Hospital. The average age was 42.5±0.6 years (range: 35 to 52 years). The duration of HIV infection was 15.6±1.2 years (range: 2 to 26 years). Transmission routes: sexual (63%) and parenteral (37%), HCV infection (42%) (90% treated). Marital status: married (62%), cohabiting (28%), living alone (10%). 78% of patients were permanently employed. All women had children, only one child was infected with HIV. The women had from one to five children (2.4±0.5 children). ART initiation after diagnosis was 7.7±1.3 years (range, 0 to 21 years). ART duration was 7.9±1.5 years (range, 1 to 19 years). The number of antiretroviral therapy (ART) regimens was 2.6±0.3 (range, 1 to 4 regimens). HIV infection stages: 3–6%, 4A–5%, 4B–2%, 4C–87% (Russian classification, 2006).
Results and discussion. All women studied were successfully receiving ART. Before ART initiation, the average HIV RNA blood level was 375,240±15,400 copies/ml. At the time of the study, HIV RNA was undetectable in the blood of all 100 patients (a decrease of 5.6 log10) (p≤0.001). Furthermore, before ART initiation, the CD4 lymphocyte count averaged 285.5±14.3 cells/μl, while at the time of the study it was 664.5±13.7 cells/μl (a 2.3-fold increase) (p≤0.001). A study of concomitant pathology revealed the following comorbidity patterns: CNS lesions (87%), cardiovascular system (65%), gastrointestinal tract (37%), kidneys (15%), bone and joint diseases (28%), endocrine system (33%), eye diseases (10%), reproductive system diseases (18%), oncology (7%), opportunistic infections (24%), and blood system diseases (18%).
Conclusion. The predominant comorbidities in women with HIV infection of childbearing age include disorders of the central nervous system, cardiovascular system, gastrointestinal tract, and endocrine system, as well as bone and joint damage. Typically, the causes of comorbid pathology are related directly to HIV, opportunistic infections, antiretroviral medications, and individual factors.
Intestinal tuberculosis (TEC) remains a disease with late verification and a high mortality rate (over 40%). The increase in the number of cases of HIV infection and immunosuppressive states determines the pathomorphosis of TEC, which requires a revision of clinical and morphological parallels.
The aim. To study the pathomorphosis of intestinal tuberculosis in modern conditions and to establish the interaction between its manifestations and the pathogenesis and immune status of patients.
Material and methods. A retrospective analysis of the diagnostic and treatment results of 217 patients with confirmed TEC was conducted (2016–2023). The morphological forms, clinical picture, HIV status, CD4-lymphocyte count, and nature of complications were assessed.
Results and discussion. All patients developed intestinal tuberculosis during the secondary period of tuberculosis infection, with 64,0% having disseminated pulmonary tuberculosis. HIV infection was detected in 60,8% of cases. The ulcerative form of intestinal tuberculosis predominated among HIV-positive patients (82,6% vs. 58,8%; p=0,00036), whereas the infiltrative and mixed forms were more common in HIV-negative patients. Diarrhea (94,9%) and intestinal bleeding (100,0%) were pathognomonic for ulcerative TEC. Complications were 2.4 times more frequently in HIV patients (p=0,003); perforation and bleeding appeared in CD4<200 cells/μL, and acute intestinal obstruction (AIO) occurred with intact immunity.
Conclusion. The morphological form of TEC reflects the severity of immunodeficiency. Ulcerative TEC should be considered as an opportunistic infection associated with HIV and severe immunosuppression. Active screening for abdominal tuberculosis is necessary in patients with disseminated pulmonary tuberculosis and HIV/TB co-infection.
Objective. The objective of the study was to evaluate the pattern of manifest herpesvirus infections in hospitalized HIV-infected patients and to identify clinical and immunological factors associated with adverse outcomes and mortality.
Materials and methods. A prospective-retrospective cohort study was conducted using data from Clinical Infectious Diseases Hospital No. 2 for the period 2018–2023. The total sample for epidemiological analysis included 46,478 patients with HIV infection (46,182 adults and 296 children). For an in-depth clinical and laboratory analysis, 530 adult patients with confirmed HIV infection and moderate-to-severe manifest Human herpesvirus (HHV) infections were selected using a census sampling method (n=530; 322 males and 208 females), including 71 fatal cases. The control group comprised 756 hospitalised patients with HHV infections without HIV infection. Because multiple concurrent herpesvirus infections were common, statistical analysis was performed both at the individual-patient level and according to the absolute number of verified clinical diagnoses. The diagnosis of HIV infection was verified using tests for antibodies to HIV-1, 2/p24 (ARCHITECT HIV Ag/Ab Combo) and a linear immunoblot («MilaBlot-HIV»). HIV-1 RNA was detected using the COBAS AmpliPrep/COBASTaqMan v.2.0 (sensitivity ≥20 copies/ml) and Abbott Real Time (≥40 copies/ml) test systems, followed by log10 transformation of the data. Viral DNA (HSV, VZV, CMV, EBV and HHV-6) was detected by polymerase chain reaction (PCR) using AmpliPrime and AmpliSens reagent kits according to the manufacturer's protocols. Immune status (CD45+/CD4+/CD8+/CD3+) was assessed by flow cytometry (Navios Beckman Coulter). The reference values from the Clinical Immunology Laboratory at the State Scientific Centre of the Institute of Immunology, Federal Medical Biological Agency of Russia, were used as the standard. Statistical analysis was performed using Excel, Statistica 12.0 and Python 3.10 (Pandas, SciPy, Statsmodels). The goodnessof-fit of the resulting logistic regression model was verified using the Hosmer–Lemeshow test (p>0.05).
Results and discussion. The proportion of Human herpesvirus (HHV) infections among hospitalized patients with HIV infection was 1.73% (530 out of 30,633). Within this infected cohort, 60.75% were male and 39.25% were female. The overall case fatality rate was 13.40% (n=71), including 37 deceased males and 34 deceased females. The mean age of patients was 42.34±0.36 years (20–76 years); no significant differences were found between genders or in relation to gender and disease outcome (р>0.05). The mean duration of HIV infection was 8.96±0.33 years and was significantly longer among deceased men (Me=11.0 years) than among women (Me=7.0 years; p=0.004), with a borderline tendency toward a longer duration among men overall (Me=8.0 years; p=0.058). ART adherence within the cohort was critically low, standing at 44.7%. Among the survivors, fewer than half of the patients were receiving treatment, with no gender differences (47.4% of men and 48.3% of women; р=0.85). In the group of fatal cases, the proportion of individuals on ART was only 25.35% (р<0.001). The absence of consistent ART is recognised as a leading risk factor for death: the presence of ART reduced the risk of death by 58% (RR=0.42; 95% CI 0.25–0.71), while the absence of regular ART increased the odds of a fatal outcome by 2.70 times (OR=2.70; 95% CI 1.54–4.76; p<0.001). The median HIV RNA level in surviving men was higher than in women, was 5.31 (4.91; 5.68) log10 copies/mL versus 5.06 (4.58; 5.32) log10 copies/mL (p=0.042). The maximum intensity of HIV replication was recorded in the fatal outcome group — 5.97 (5.72; 6.11) log10 copies/mL (р<0.001 compared to survivors) — which was associated with the absence of ART in 74.6% of those who died. The leading cause of hospitalisation was herpes zoster (50.29%), followed by CMV (24.14%) and herpes simplex (HS, 19.19%). Among men, there was a tendency for herpes zoster to predominate (53.04% vs 45.99%; р=0.076), whilst among women, HS monoinfections were more common (21.23% vs 13.71%; р=0.049). Herpes zoster dominated the pattern of monoinfections (67.51%), ahead of HS (16.50%) and CMVI (15.99%). Among the deceased (105 diagnoses in 71 patients), CMVI was the most common (41.90%), ahead of herpes zoster (28.57%) and HS (23.81%). The odds of a fatal outcome in patients with CMV monoinfection were 6.72 times higher than in those with other herpesvirus monoinfections (95% CI 3.84–11.76; p<0.001), with the highest proportion observed among females (42.86%). The immune status of HIV-infected patients differed significantly from that of the HIV-negative control group (р<0.0001): a deficiency in total lymphocytes and CD4+ T-lymphocytes, accompanied by a decrease in the IRI and an increase in the percentage of cytotoxic CD8+ T-lymphocytes. ROC analysis verified the immunoregulatory index (IRI) as a highly accurate predictor of mortality (AUC=0.826, р<0.001) with a critical cut-off value of ≤0.43 (sensitivity 92.3%, specificity 70.6%). The most pronounced changes were observed in fatal cases: a drop in the lymphocyte percentage to a median of 13.5% (7.7; 18.8), a critical deficiency of CD4+ T-lymphocytes (relative count down to 10.0% (7.0; 13.0), absolute — down to 78.0 (50.0; 102.0) cells/mL) and a decrease in the IRI to 0.28 (0.18; 0.36) (р<0.001 compared to survivors), which confirms the IRI as a predictor of poor outcome. To eliminate multicollinearity, the calculated IRI index was excluded from the final multivariate logistic regression model (Logit model). Multivariate logistic regression confirmed that the absolute CD4+ T-lymphocyte count is the strongest independent predictor of fatal outcome: OR=0.70 (95% CI 0.51–0.97; p=0.038).
Conclusion. Thus, non-adherence to the required regular ART (25.35%) was significantly associated with an increased risk of mortality among HIV-infected patients with HHV coinfection against the background of severe immunodeficiency.
EPIDEMIOLOGY
The aim of this study was to evaluate the epidemiological characteristics of patients in multidisciplinary hospitals of a large metropolis (Moscow) and assess the representativeness of the data for estimating current trends in HIV prevalence in Moscow.
Materials and methods. At the first stage of the study, the hospitalised contingent of Moscow multidisciplinary hospitals was characterized, including their socio-demographic data, as well as their affiliation with the profile of specialised medical care. Then, after assessing the representativeness of the sample, the prevalence of HIV infection among the adult Moscow city population was estimates. Continuous variables between groups were compared using Student’s t-test. Categorical variables between groups were compared using appropriate criteria (the Fisher’s exact test with Bonferroni multiplicity correction and the Pearson’s chi-squared test). A p-value <0.05 was considered statistically significant.
Results and discussion. The prevalence of HIV infection in the hospitalised population was 0.39% (95% CI: 0.37–0.41%). The highest HIV prevalence (p<0.01) was found in the profiles: Toxicology, Psychosomatics, Purulent surgery, Therapy and Intensive care. The lowest prevalence was noted for the profiles of Oncology, Gynecology and Cardiology. Among all patients in multidisciplinary hospitals with detected HIV infection, the largest proportion was accounted for by residents of Moscow — 51.96%; among newly diagnosed HIV infected patients — by non-resident citizens (43.24%). The estimated number of adult people living with HIV (PLWH) in Moscow was 42 271.
Conclusions. Thus, 96% adult of PLWH in Moscow are aware of their HIV status, which marks the effective work of the health care system on HIV infection in Moscow.
The аim. To study the incidence of tuberculosis and the formation of its structure among the elderly in Russia, the Central Federal District and the Yaroslavl Region, in dynamics for 2014–2023.
Materials and methods. Data from the Federal statistical observation form No. 8 and Rosstat data on the population of Russia, for 2014–2023. The Statistica 15.0 software and spreadsheets in Excel 2019 format were used for the analysis. The differences were recognized as significant at a value of p<0.05.
Results and discussion. Despite the decrease in the incidence of TB in 2014–2023 in Russia, the Central Federal District and the Yaroslavl Region, the proportion of patients aged 65 years and older in the structure of newly diagnosed TB patients increased 1.5–1.9 times during this time. Respiratory TB prevailed among patients of this age group, and the proportion of extrapulmonary forms of TB in Russia and the Central Federal District did not exceed 6–7%, and in the Yaroslavl region in 2020, 2022, 2023, not a single patient with extrapulmonary forms of TB was identified. This situation indicates a decrease in alertness among doctors of various specialties regarding the detection and diagnosis of extrapulmonary forms of TB among the elderly. The detection of common forms of TB with bacterial excretion in half of patients aged 65 years and older, both in Russia, the Central Federal District and the Yaroslavl region, indicates serious shortcomings in the organization of screening among the older age groups of the population. The late diagnosis of TB and the high epidemic risk of TB spread among the elderly are also indicated by the increase in the proportion of postmortem TB cases, which increased by an average of 1.5 times in Russia and the Central Federal District from 2014 to 2023, and ranged from 0 to 14.8% in the Yaroslavl Region.
Conclusion. Currently, in Russia, the Central Federal District and the Yaroslavl region, there is a shift in the epidemic process towards older age groups, which indicates the increasing importance of the cohort of elderly patients in the formation of the TB incidence rate. In this regard, there is an urgent need to improve organizational approaches to the organization of screening aimed at early detection of TB among older age groups of the population.
ОРГАНИЗАЦИЯ МЕДИЦИНСКОЙ ПОМОЩИ
Chronic hepatitis C (HCV-infection) continues to be a serious medical, social and economic problem worldwide, which requires improved approaches to its diagnosis, treatment and prevention.
The aim of the study: to create prognostic models of the epidemic situation of chronic hepatitis C in the Arkhangelsk region and their pharmacoeconomic assessment to select the optimal strategy for providing medical care to HCV-infected patients.
Materials and methods. To build prognostic models of the development of the epidemiological situation of chronic hepatitis C, a mathematical model, that was developed and described by Razavi H. et al. was used.
Results and discussion. According to calculations of the mathematical model, while maintaining existing approaches to the diagnosis and treatment of chronic hepatitis C, the number of infected people in the Arkhangelsk region will continue to grow and will reach up to 27,080 people by 2030. With timely measures to expand the availability of antiviral therapy for the population, it is possible to achieve WHO-recommended targets by 2030 to reduce the number of new infections by 90% and deaths from HCV-infection by 65%.
Conclusion. We have shown that the WHO strategy is the most appropriate scenario for providing medical care to patients with chronic hepatitis C, as it significantly reduces the burden of this disease in the Arkhangelsk region.
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