The lecture, based on international and our own scientific and clinical experience, examines aspects of epidemiology, features of clinical manifestations, diagnostics, and treatment of HIV infection in children. It covers complex issues related to the study of adverse events associated with the use of antiretroviral drugs, disorders of various organs and systems directly or indirectly related to the effects of HIV, drugs, and comorbid pathological processes. It presents materials related to the problem of cardiovascular diseases, the risk of which in children increases with age, the duration of HIV infection, and the duration of antiretroviral therapy. It emphasizes the importance of metabolic disorders (impaired lipid and glucose metabolism), the role of endothelial cell damage and dysfunction of the vascular endothelium of the heart and brain in the early development of cardiovascular diseases in children, and proposes an algorithm for providing assistance to children with HIV infection and dyslipidemia during antiretroviral therapy. The lecture is intended for a wide range of specialists, residents, and students of medical universities.

The aim: to assess the prevalence and genetic diversity of high-risk human papillomavirus (hrHPV) in intraepithelial lesions of the cervix of varying severity in women (using the Gomel region as an example).

Materials and methods. Cytological examination and testing for HPV were carried out from 2018 to 2021 using the Abbott RealTime hrHPV kit for high-risk HPV on the Abbott m2000sp device. This test separately detects HPV 16, HPV 18 and a pool of 12 additional hrHPV types, further genotyping was carried out using the AmpliSens hR HPV genotype-FL reagent kit (Russia). Material — scrapings from the cervical canal. 11 146 women from the Gomel region were examined.

Results. According to the results of the studies, high-grade dysplasia (HSIL) was noted in 1.0% of cases, low-grade dysplasia (LSIL) — in 1.3% and atypical squamous cells of unknown significance (ASC-US) — in 1.8% of samples. A significant relationship between HPV and cervical dysplasia of varying degrees was established. In severe cervical dysplasia, HPV type 16 was identified in 69.2% of cases (p=0.027). In mild cases, type 45 was detected in 18% (p=0.001) and type 56 in 22.0% (p=0.010). The proportion of HPV 18 (18.5%) was significantly higher in the group of women with a normal cytogram (p < 0.001). No statistically significant differences in the frequency of occurrence of other HPV genotypes were found. In women of the Gomel region, with varying degrees of dysplasia, the dominance of HPV of the phylogenetic group a9 was noted, while in the group of women with HSIL, their share was maximum — 82.4%. HPV-associated dysplasia of the cervix was detected in 51% of women of reproductive age (p < 0.001).

Conclusion. The relationship between high-risk carcinogenic HPV and the development and progression of cervical intraepithelial dysplasia of the cervix has been demonstrated. It has been established that the genetic landscape of dominant HPV variants differs in women with different degrees of cervical dysplasia. Among women with cervical dysplasia, the dominance of HPV of the phylogenetic group a9 was noted, which was maximally represented in the group with HSIL. HPV screening and liquid cytology are important components of the program for early detection of neoplastic processes aimed at preventing cervical diseases caused by HPV.

Aim of the study: to assess quantitative and qualitative indicators of HIV drug resistance to antiretroviral drugs in patients with virological failure of first-line ART.

Materials and methods. Clinical and laboratory parameters and results of HIV molecular genetic testing were analyzed in 964 patients with virological failure of antiretroviral therapy (ART) in 2018–2022 at the St. Petersburg AIDS Center.

Fragments of the pol gene encoding HIV enzymes were examined by PCR and Sanger sequencing. Identification of HIV drug resistance mutations to antiretroviral therapy was performed using the Stanford University HIVDB algorithm Version 9.4.1. The dynamics of HIV resistance prevalence among ART recipients were assessed by comparing the results of two studies: a retrospective study (2006–2011) and a current study (2018–2022) in St. Petersburg.

Results and discussion. Virological failure was associated with the development of HIV resistance mutations in 76.5% of patients. HIV resistance mutations were found in the majority of cases (93.9%) in patients receiving first-line ART. Regimens consisting of 2 nucleoside reverse transcriptase inhibitors (NRTI) + non-nucleoside reverse transcriptase inhibitors (NNRTI) combination were more frequently used (72.1%), the proportion of first-generation NNRTI class drugs was 58,7%.

According to the results of HIV resistance testing, resistance to the NRTI (90.6%) and NNRTI (78.3%) classes was more common than to protease inhibitors (PI) (3.8%) and integrase strand transfer inhibitors (INSTI) (0.9%). HIV resistance to two drug classes was found in 74,2% of patients, most frequently to the NRTI+NNRTI classes (71.3%). Multidrug resistance to three drug classes (NRTI+NNRTI+PI) was rarely detected, only in 1.3% of patients.

Analysis of HIV resistance to antiretroviral drugs in patients over time showed an increase in resistance to NRTIs (from 79.8% to 90.6%) and NNRTIs (from 60.4% to 78.3%), comparing the periods 2006–2011 and 2018–2022. There was also a decrease in the number of patients with resistance to PIs (from 19.9% to 3.8%).

Conclusion. Our study shows that acquired HIV drug resistance was the leading cause of virological ineffectiveness of antiretroviral therapy between 2018 and 2022. Importantly, the majority of HIV drug resistance was observed in patients receiving first-line therapy.

These findings highlight the need to modernize first-line ART regimens, including the wider introduction into clinical practice of drugs with a high genetic barrier to resistance. These include modern integrase inhibitors or protease inhibitors. The choice of ART regimen should be based on the patient’s previous drug history and HIV resistance indicators. When selecting a new regimen plan for patients with multidrug-resistant HIV, it is essential to use at least two or three medications (typically from different classes) that do not have any resistance mutations.

The aim. To determine the HIV-1 drug resistance profile in patients with virological failure to elsulfavirine-containing antiretroviral therapy in a real-world clinical setting.

Materials and methods. The study group consisted of HIV-1 nucleotide sequences (pol gene fragments encoding protease and part of reverse transcriptase) from 179 HIV-infected patients with virological failure of elsulfavirine-containing antiretroviral therapy and who had not previously received other non-nucleoside reverse transcriptase inhibitors. Resistance mutations were identified and HIV-1 drug resistance was determined using the HIVdb database (v. 9.8).

Results and discussion. HIV-1 mutations associated with viral resistance to non-nucleoside reverse transcriptase inhibitors were detected in 88.3% of patients with virological failure of elsulfavirine-containing antiretroviral therapy. Previously described HIV-1 resistance profiles to elsulfavirine were detected in only 5.1% of the studied patients. A total of 29 mutations were detected, the most common being V106I (46.9%), E138K (38.5%), H221Y (34.6%), E138Q (20.7%), F227C (12.3%), Y181C (11.7%), K101E (11.2%), and E138A (10.6%). A total of 87 different HIV-1 mutation patterns were detected, with combinations of two or more mutations predominating (70.9%). The main patterns detected included combinations of mutations V106I/M, E138K/Q/G, and H221Y±K101E, F227C, G190S, and M230L. High levels of HIV-1 resistance in the studied patients were most frequently detected to rilpivirine (60.9%), which limits its successful use in patients taking elsulfavirine, and least frequently to doravirine (22.9%) and etravirine (9.5%), which allows them to be considered as options for switching.

Conclusion. This study identified the main mutations associated with elsulfavirine-containing therapy failure, potential pathways for the development of HIV-1 resistance to the drug, and HIV-1 cross-drug resistance to other drugs in class. However, most of the patterns identified in this study have not been previously described, indicating the need to update data on the HIV1 resistance profile to elsulfavirine.

The aim of this study was to examine the genotypic and allelic distribution of certain polymorphic variants of the IFNAR1 gene in HIV-positive patients and evaluate their association with HIV infection.

Materials and methods. The study material consisted of whole blood samples obtained from HIV-infected individuals with virological failure of antiretroviral therapy (n=378) and apparently healthy individuals (n=319). We performed sequencing of all exons of the IFNAR1 gene with partial coverage of flanking intronic sequences, including analysis of the promoter region and a substantial intronic segment in the pre-promoter region, followed by analysis of the obtained nucleotide sequences.

Results and discussion. We demonstrated statistically significant associations with HIV infection for three polymorphic variants of the IFNAR1 gene: rs2843710 (–654 C/G), rs2257167 (exon 4, 18339G>C: Val168Leu), and rs2856973 (intron 10, 28767 A>T). The genotype distribution of all studied polymorphic variants in the analyzed groups conformed to HardyWeinberg equilibrium. Significant differences in genotype distribution were shown between HIV-infected individuals and the control group: rs2843710 — х²=9.624 at p=0.0081; rs2257167 — х²=8.623 at p=0.0134; rs2856973 — х²=10.447 at p=0.0054. The homozygous C/C genotype and minor C allele of rs2257167 locus were associated with predisposition to HIV infection, while the G/G (rs2843710) and T/T (rs2856973) genotypes along with their corresponding G and T alleles demonstrated a pronounced protective effect.

Conclusion. This study reveals an association between IFNAR1 gene polymorphisms and a predisposition to HIV infection, demonstrating their significant, albeit non-exclusive, role in the disease development.

The aim. To evaluate the prevalence of secondary latent HCV infection, as well as the dynamics of hepatic fibrosis and extrahepatic manifestations in patients who achieved HCV RNA aviremia after a course of primary interferon-free therapy.

Material and methods. A retro- and prospective single-center exploratory study was conducted with the participation of 125 patients with chronic HCV infection who underwent in-depth examination and received treatment at a non-governmental medical clinic in St. Petersburg in the period from 2015 to 2024. Changes in clinical and laboratory markers of liver fibrosis and extrahepatic manifestations were evaluated in dynamics. HCV eradication was achieved in the absence of HCV RNA in blood plasma and peripheral blood mononuclear cells (PBMCs).

Results and discussion. The study showed a significant effect of HCV eradication on the regression of fibrotic and dystrophic changes in the liver (63.4% of patients had regression of liver fibrosis; p < 0.05), as well as normalization of biochemical parameters and markers of HCV-associated LGSI syndrome (Low Grade Systemic Inflammation). After HCV eradication, 32% of patients retained the laboratory phenomenon of asymptomatic mixed cryoglobulinemia or a symptom complex of cryoglobulinemic vasculitis. The prevalence of secondary latent HCV infection after a course of treatment with direct antiviral drugs (DAAs) was 4.8%, and its outcomes were recurrence of viremia, spontaneous clearance of HCV RNA, and persistence of HCV RNA in PBMCs. The absence of regression of liver fibrosis, extrahepatic manifestations, and normal liver function can be considered potential predictors of the transformation of the viremic form of chronic HCV infection into a secondary latent HCV infection.

Conclusion. Thus, in patients with chronic HCV infection, along with the systemic positive effect of the course of primary interferon-free therapy and the achievement of HCV RNA aviremia, in some cases (4.8%) there is a lack of immunological (incomplete immunological response) and virological response. The results obtained in patients in the near and long-term follow-up periods are of certain clinical and epidemiological interest, indicate the expediency of optimizing outpatient follow-up to assess the risks and likelihood of developing secondary latent HCV infection after a course of interferon-free therapy, and the need for further multicenter studies.

The aim of the study. To determine the diagnostic significance of recombinant tuberculosis allergen and T-SPOT for the diagnosis of tuberculosis in patients with HIV infection.

Materials and methods. In 25 patients (72.0% (18/25) male and 28.0% (7/25) female), who had verified tuberculosis in combination with HIV infection, an immunological study was performed using the recombinant tuberculosis allergen and the TSPOT test. The statistical modeling method was simple logistic regression, calculating the likelihood ratio for intervals of the number of CD4 lymphocytes.

Results and discussion. From the CD4 lymphocyte level of 200 cells/ml, the probability curve of a positive test result with the recombinant tuberculosis allergen increases sharply and, starting from the CD4 lymphocyte level of 600 cells/ml (the minimum threshold of a healthy person), takes on a probability close to 1.0 (100%). For the T-SPOT immunological test, the probability curve of a positive test result is more than 50% at a CD4 lymphocyte level of less than 200 cells/mll, approximately 100 cells/mll, and at a CD4 lymphocyte level slightly above 200 cells/ml, the probability curve approaches 1.0 (100%).

Conclusion. In diagnostically difficult cases in a patient with HIV infection, it is preferable to use an immunological test with T-SPOT to detect tuberculosis when the number of CD4 lymphocytes decreases to less than 200 cells/ml.

The aim: was to investigate the dynamics of the IFN-γ/IL-10 ratio during the intensive phase of chemotherapy in patients with pulmonary tuberculosis.

Materials and methods. The study group is represented by 100 patients suffering from pulmonary tuberculosis (newly diagnosed pulmonary tuberculosis — 60 people, chronic pulmonary tuberculosis — 40 people). Serum cytokine concentrations were determined by enzyme-linked immunosorbent assay.

Results and discussion. It was found that in the case of the «effective» intensive phase of chemotherapy in patients with pulmonary tuberculosis, the ratio IFN-γ/IL-10 tended to increase from 0.183±0,01 to 0.233±0,02, and in the case of the «ineffective» phase of chemotherapy, this ratio tended to decrease from 0.3±0,015 to 0.2±0,011.

Conclusion. The ratio of IFN-γ/IL-10 during the intensive phase of chemotherapy in patients with pulmonary tuberculosis can be used as an additional marker of the effectiveness of chemotherapy in patients with pulmonary tuberculosis.

The aim of the study is to analyze the impact of combined pathology of HIV and tuberculosis on the effectiveness of tuberculosis treatment and assess direct budgetary costs for the treatment of patients with combined infection of HIV and tuberculosis in the Republic of Karelia.

Materials and methods. A retrospective analysis of the results of tuberculosis (TB) treatment was conducted among 228 newly diagnosed patients with HIV and TB co-infection in the Republic of Karelia from 2001 to 2022. The results of tuberculosis chemotherapy were analyzed as a comparison group, among 228 newly diagnosed HIV-negative tuberculosis patients.

Results and discussion. Significantly lower rates of chemotherapy effectiveness in patients with HIV and TB co-infection (52.2%) than in HIV-negative TB patients (64%) (p < 0.05) were associated with significantly higher mortality (25.4%) than in the group with TB and HIV-negative status (15%) (p < 0.05) and a higher rate of treatment interruptions (15.8% and 13.2%). Additional reasons for high mortality in the group with HIV and TB co-infection were the causes of death from HIV infection in 29 (50%) of 58 people, as a result of its late diagnosis and low adherence to antiretroviral therapy (ART). The highest budget costs in combination with low treatment effectiveness, high mortality, and frequent interruptions from treatment were observed in the group of patients with co-infection of HIV and tuberculosis with MDR MBT (multi-drug-resistant MBT) and pre-XDR (multi-drug-resistant MBT and drug resistance to ofloxacin) — up to 1,404.2 thousand rubles per 1 effectively cured person in 2023 prices. The costs of ART ranged from 17.1 to 57.1 thousand rubles, which was from 3.9 to 5.4% in the structure of costs for the treatment of patients with HIV and tuberculosis. In the structure of costs, a significant place was occupied by costs associated with a long stay of patients in hospital from 105.4 to 127.5 bed-days, which was from 234.3 to 283.4 thousand rubles per 1 patient, which was largely due to the lack of rapid molecular genetic methods for determining drug resistance to the main anti-tuberculosis drugs, delays in the correction of effective chemotherapy, and shortcomings in the organization of chemotherapy at the place of residence.

Conclusion. The reserves for reducing budget costs, reducing mortality and increasing the effectiveness of treatment of patients with co-infection of HIV and tuberculosis are measures to improve the detection and monitoring of patients with HIV, increasing their adherence to ART, the introduction of rapid molecular genetic methods for determining drug resistance of MBT in tuberculosis patients and improving the organization of chemotherapy for TB patients at their place of residence.

The aim of the study was to investigate the characteristics of treatment adherence, the unmet needs in the socio-economic domain, and to determine the presence of an association between these factors during the intensive phase of chemotherapy in patients with tuberculosis exhibiting preserved drug sensitivity of the pathogen.

Materials and methods. The study involved patients aged 26 to 67 years (N=130, M_age=42.9 years, SD=9.6) with a newly established diagnosis of drug-sensitive respiratory tuberculosis at the start of the intensive phase of treatment. Psychodiagnostic methods included the «Compliance Level» technique by R. V. Kadyrov, O. B. Asriyan, and S. A. Kovalchuk; the «Level of Social Frustration» scales (USF-1, USF-2). Data analysis comprised descriptive statistics (frequency analysis) and correlational analysis (methods of paired and partial correlations). Data processing — IBM SPSS Statistics version 27.

Results and discussion. A diffuse type, oriented towards mechanistic adherence to the physician’s prescriptions, characterizes patients’ attitudes toward the illness. It was established that treatment adherence in patients with drug-sensitive respiratory tuberculosis during the intensive phase of chemotherapy is closely associated with the level of dissatisfaction in the socio-economic domain of life.

Conclusions. The complex of frustrations and barriers identified during the study exerts a direct negative impact on patients’ adherence to treatment, which in turn underscores the necessity for social and clinical-psychological support for patients from the very first day of anti-tuberculosis chemotherapy. Which, in turn, will make the tuberculosis treatment process less psychologically traumatic for the patient, reduce the level of dissatisfaction, and strengthen treatment adherence.

The aim of this study was to investigate risk factors that influence the epidemic effectiveness of antiretroviral therapy.

Materials and methods. Data on incidence, prevalence, mortality, the number of new HIV infections, the number of deaths from HIV-infected individuals, the number of people living with HIV (PLHIV), the number of patients receiving antiretroviral therapy (ART), and viral load (VL) and immune status (IS) testing results were analyzed.

Results and discussion. Antiretroviral therapy has been used in the Vologda Oblast for 19 years and, in 2023, covers 82.1% of the total number of people living with HIV and 86.1% of patients registered for dispensary care. Based on an analysis conducted in the region between 2005 and 2023, the number of people living with HIV increased by 4.1 times, while the number of patients registered for follow-up care increased by 5.5 times. All patients were eligible for treatment monitoring, and 94.8% were tested for viral load. During this period, a positive impact of antiretroviral therapy on the HIV epidemic has been observed, as evidenced by a decrease in the number of new cases and the number of patients not registered for follow-up care. It is also worth noting the increase in the proportion of patients in the clinical manifestation stage, which increased from 25% to 50%. The effectiveness of ART is negatively impacted by factors including incomplete ART coverage among PLHIV under clinical observation (86.1%), a long period of therapy initiation from diagnosis (averaging 358 days), non-adherence to therapy among PLHIV (33.1%), and the achievement of an undetectable viral load in only 80.8% of PLHIV.

Conclusion. An analysis of the development of HIV infection in the Vologda Oblast demonstrates a positive impact of the widespread use of antiretroviral therapy on the incidence rate, with stabilization noted. Currently, the epidemic can be classified as developing severe and comorbid forms of HIV. No reduction in HIV-related mortality has been observed with the use of antiretroviral therapy. Even with full treatment coverage, comprehensive organizational and preventive programs are necessary to impact the epidemic.

The aim. To study and analyze the main causes of death of patients with HIV infection who died in the hospital of the St. Petersburg AIDS and Infectious Diseases Center, taking into account the stage of the disease and the duration of the disease, opportunistic and other comorbid pathology, and the use of antiretroviral therapy (ART).

Materials and methods. For the period from 2016 to 2023, an analysis of hospitalizations of patients in the AIDS Center hospital and an analysis of fatal outcomes was conducted based on hospital records, statistical reports, pathological protocols, and protocols of commissions for the study of fatal outcomes. A retrospective analysis of 397 medical histories of deceased patients was conducted.

Results and discussion. During the analyzed period, 397 patients died, of whom 74% were treated in the intensive care unit, 4% were died within the first 24 hours of stay; 17% of patients were sent to the palliative care unit; 86% died in the progressive stages of HIV infection, in 73% opportunistic diseases (OD) played a major role in fatal outcomes, concomitant pathology was recorded in 98%. Among patients who died in stage 4V (Clinical classification of HIV infection, Russia, 2006) due to the development of opportunistic diseases, the average CD4 lymphocyte count was 75.9 cells/μl, the amount of HIV RNA in the blood was 6811 33.18 cop/ml. More than a third of deceased patients had several competing diseases that served as the cause of death. In the structure of causes leading to death, the leading role was played by central nervous system (CNS) lesions of various origins (46.8%); pneumonia — 32.5%, including pneumocystis pneumonia — 11.3%, mycobacteriosis — 7%, oncohematological diseases — 19.6%, chronic viral hepatitis in the stage of decompensated liver cirrhosis — 22.7%.

Conclusion. The development of adverse outcomes in HIV-infected patients is influenced by a number of factors: progression of HIV infection (stage 4V, low immune status, high viral load), development of severe generalized opportunistic diseases, especially several competing forms, concomitant pathology, non-adherence to dispensary observation and treatment, absence/late onset, irregularity, interruption of antiretroviral therapy and drugs for the prevention of opportunistic infections, unfavorable social status.

The incidence rate of tuberculosis in the Russian Federation in 2022 was 31.3 per 100 thousand people. At the same time, in some regions this figure exceeds the average for the Russian Federation by 2 times or more. Analysis of the epidemiological situation of HIV infection shows a relationship between the prevalence of HIV infection in the regions and the incidence rate of tuberculosis, the proportion of HIV-infected patients among newly diagnosed cases of tuberculosis and HIV-infected patients among patients who died during the year with a diagnosis of tuberculosis.

The aim. To study the contingent of patients with tuberculosis combined with HIV infection in a region with a high prevalence of HIV infection, to determine the causes of death of patients with tuberculosis combined with HIV infection within a year after its detection and posthumous diagnosis, to determine the correctness of the criteria for assessing anti-tuberculosis care in conditions of high prevalence of HIV infection.

Materials and methods. In a region with a high prevalence of HIV infection, all cases of tuberculosis combined with HIV infection were studied from February to October 2023 (148). A separate analysis of data on deceased patients was conducted (the main and immediate cause of death, the presence of other secondary HIV infections were studied). Results and discussion. The contingent of patients with tuberculosis combined with HIV infection in the region in all main categories remains the same as in previous years in the Russian Federation (except for age). In all cases, the cause of death of patients with tuberculosis, both posthumously and within a year after its detection, was very rapid progression in the late stages of HIV infection. In 19.0% of cases, tuberculosis could not be considered the cause of death, since, despite the presence of generalized tuberculosis, other secondary diseases were simultaneously present, equally influencing the outcome.

Conclusion. Considering all of the above and taking into account that in the Russian Federation more than a quarter of tuberculosis patients have HIV infection, the criteria for assessing the work of the TB service with HIV patients should be defined separately. A separate reporting form should be created to analyze statistical data on cases of tuberculosis combined with HIV infection.