Preview

HIV Infection and Immunosuppressive Disorders

Advanced search
Vol 16, No 4 (2024)
View or download the full issue PDF (Russian)
https://doi.org/10.22328/2077-9828-2024-16-4

JUBILEE

EDITORIAL ARTICLE BASED ON THE RESULTS OF THE STUDY

7-16 186
Abstract

Aim of the study: to investigate the role of proinflammatory markers and some immune cells in neural and cognitive disorders in long COVID patients.

Materials and methods. The study included 81 patients diagnosed with long COVID, the presence of which was determined by the persistence of a complex of multidirectional symptoms for more than 12 weeks that developed during or after COVID-19. Flow cytometry was used to assess lymphocyte subsets. The main lymphocyte subpopulations were analyzed: T cells, cytotoxic T cells, B cells, NK and NKT cells in blood plasma via multiplex xMAP analysis. Also concentrations of GM-CSF, IL-1, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12, IL-13, IL-17, MCP-1, MIP-1b, TNF were measured. The content of proinflammatory cytokines and some immune system cells was characterized in respondents with long COVID. A comparative analysis of data was conducted with individuals without a history of COVID-19, as well as between patients with different numbers of SARS-CoV-2 cases.

Results and discussion. The study identified characteristic features of long COVID that affect both the nervous and immune systems.

Analysis of the blood cells revealed absolute and relative lymphopenia due to a decrease in NK cells. We also noticed an increased number of NKT cells in patients who suffered multiple COVID-19, when compared to those who only were infected with SARS-CoV-2 once. Cytokine analysis revealed increase in concentrations of IL-5, IL-8, IL-13, IL-17 and CCL2/MCP1 in blood plasma of long COVID patients.

Conclusion. The data provides additional support to the theory of immune dysregulation in neurological symptoms of long COVID.

ANALYTICAL REVIEW

17-27 226
Abstract

Over the past 30 years, the amount of sequencing data has increased significantly, including for human immunodeficiency virus type 1 (HIV-1). Significant developments have also occurred in the field of bioinformatics. Because of this, first in science and then in practical healthcare, a new field has emerged — genomic surveillance. Currently, the possibilities of using bioinformatics methods are practically not described in Russian regulatory documents. This review outlines the main applications of genomic surveillance of HIV infection: analysis of HIV-1 drug resistance, investigation of HIV transmission, study of the characteristics of HIV occurrence and spread, assessment of the effectiveness of HIV prevention interventions, retrospective and operational analysis of the dynamics and structure of morbidity, and forecasting the development of the epidemic process. The review presents successful examples of domestic and international research, and makes proposals for the introduction of bioinformatics methods into the Russian system of epidemiological surveillance of HIV infection.

ORIGINAL STUDIES

28-44 103
Abstract

The aim of the study was to search for candidate genes interacting with HIV attachment receptors (CCR5, CXCR4, CCR2, CD4) and potentially involved in disease pathogenesis, based on complex in silico network algorithms.

Materials and methods. A number of web applications were used to analyse genetic and protein-protein networks, the algorithms and databases of which are complementary. The CD4 receptor and chemokine co-receptor genes CCR5, CXCR4 and CCR2 were used as background/baseline genes in all cases, as their protein products play a key role in the process of virus attachment to the cell. The data were analysed, including a two-stage ranking of the identified candidate genes according to their interaction with background genes and their presence in the results of network analysis of different web resources.

Results and discussion. According to the results, candidate genes were identified using three web resources: HumanNet — 451 candidate genes, GeneMania — 86, STRING — 61. Based on the results of crossing the three web resources, the total number of candidate genes associated with background genes was 511. The total number of genes with a rank above 4 points was 68. Of these, 31 genes (45.6%) encoding C-C/C-X-C family chemokine ligands, 12 genes (17.6%) encoding C-C/C-XC receptors, 8 genes (11.8%) encoding receptors of other types, and 17 genes (25%) encoding proteins of other types. The following receptors and proteins that are not members of the C-C/C/C-X-C families of the indicated groups have been identified: ARRB2, TLR2, ADRA1A, ARRB1, FPR1, FPR3, GNAI1, PF4, PIK3CG, PPIA, S1PR3, GNA11, GNAI2, GNG2, PTPRC, ADRA1B, ADRB1, AFP, CD164, DBN1, GNB1, ITCH, RNF113A, SLC1A1, USP14.

Conclusion. Most of the identified candidate genes interacting with HIV attachment receptors and potentially involved in the pathogenesis of the disease were those encoding chemokine receptors and their C-C/C-X-C family ligands, the role of which in the progression of HIV infection is known or under active investigation. At the same time, genes whose products have never been considered as possible participants in the pathogenesis of the disease were identified, but the results suggest that they may play a role in the regulation of virus entry and/or in the modulation of the immune response of the organism. Further bioinformatic and experimental studies of the functions and polymorphic variants of these genes will help to improve the understanding of the genetic basis of HIV pathogenesis and identify new directions for therapeutic approaches.

45-54 96
Abstract

Aim of the study. Comparative analysis of clinical manifestations and laboratory indicators of acute HIV infection in patients detected in different epidemic periods with a 10-year difference (2008–2013 and 2018–2022).

Materials and methods. An analysis of 142 inpatient records of patients detected in the acute stage of HIV infection in the period from 2008–2013 in the ‘Botkin Clinical Infectious Diseases Hospital’ (‘Botkin Hospital’) and 110 outpatient records of patients detected in the “Centre for the Prevention and Control of AIDS and Infectious Diseases” (“Centre for the Prevention and Control of AIDS and Infectious Diseases”) was conducted., in whom acute stage of HIV infection was detected from 2018– 2022 in “Botkin Hospital”. We evaluated clinical and laboratory results of patients in different years of infection.

Results and discussion. Over the ten years of the HIV epidemic in the city of St. Petersburg, new trends in the clinical picture of the acute stage of HIV infection can be found. Over the period 2018–2022, the overall intoxication syndrome severity decreased: fever was more often febrile (72%), lasting from 3–5 days, myalgia — 20%, arthralgia — 15%, mouth mucosal aphthae were found in 7% of patients, skin rashes were observed only in 34%, and lymphadenopathy — 30%. Gastrointestinal disorders were also noted in 28%. Of the secondary and opportunistic infections, OPC prevailed in 83%, oesophageal mycosis in 17%, and serous meningitis in 17%. The median CD4-lymphocyte count was 24–573 kL/μL.

Conclusion. the data obtained show that the acute stage of HIV infection has become easier, with a decrease in the intensity and duration of the febrile period, less frequent skin manifestations, secondary diseases, and higher CD4 lymphocyte counts. As a result, diagnosis of the acute phase of HIV infection is difficult for primary care physicians. In any person presenting with signs or symptoms of a viral infection (influenza, infectious mononucleosis, rubella, enteroviruses, etc.), acute HIV infection must be included in the differential diagnosis.

55-65 123
Abstract

Aim of the study. To analyse the incidence and pattern of emotional suffering and internalised stigma, as well as their impact on adherence to antiretroviral therapy (ART) in young patients living with perinatal HIV infection.

Materials and methods. We studied 105 patients with perinatal HIV infection (53 men (50.4%) and 52 women (49.6%)), describing their medical, social and laboratory characteristics such as CD4-lymphocyte count (cells/μL) and HIV RNA detection (copies/mL) in blood at the moment of their transition to adult follow-up and 3 years afterwards. We performed an in-depth crosssectional psychological and psychometric study of 41 patients aged 18–25 (23 men (56%) and 18 women (44%)) with perinatal HIV infection monitored since childhood at the dispensary department of the AIDS Centre. The following methods were used: the HADS scale (Hospital Anxiety and Depression Scale, 1983), the “Major Stigma Factor Test” (2015) with questions adapted for HIV disease and the Morisky-Green Medication Adherence Scale. A survey of 105 patients with HIV PPI was conducted: 53 men (50.4%), 52 women (49.6%), their social status and the course of HIV infection were characterized (the number of CD4 lymphocytes (cells/μL) and HIV RNA in blood plasma (copies/mL) retrospectively at the age of 18 on the moment of transition to an adult dispensary and in dynamics (~ 3 years later). Then 41 patients aged 18–25 years (23 (56%) men, 18 (44%) women) were selected from the main group using a continuous method and an in-depth cross-sectional psychological and psychometric examination was conducted using the HADS scale (Hospital Anxiety and Depression Scale, 1983); “A test to identify the leading factor of stigmatization” (2015) [with modification of questions for HIV infection; adherence assessment scales (Morisky-Green)].

Results and discussion. The incidence of stigma/internalised stigma was more frequent in men than in women and was associated with long-term ART intake. All other stigma/internalised stigma factors (individual, family/friends, social) were not statistically significant. Depressive states were more often found in women than in men. Our ART adherence analysis did not yield statistical differences. The average age of patients at the time of the study was 20.9±1.5 years. The duration of the disease is comparable to the age of the study group which is due to infection. The average age of HIV infection detection was 2.5±4.2 years. In 79% of patients ART was started at the age of 7.2±4.5 years. According to the results of the patient survey, 5.8% of respondents created their own family (including with the birth of 1 child), and only one in five (20%) reported having a job, 8.6% had a disability. The existing dependence on nicotine, as well as the experience of alcohol and drug consumption (recreational use) were noted in 12.3%, 4.7 and 2.8% of patients, respectively.

Conclusion. This study showed correlations between decreased adherence to ART, emotional suffering and internalised stigma in patients with perinatal HIV infection. Psychocorrection and psychopharmacological treatment may prove effective for stabilising patients’ mental state, reducing internalised stigma factor and consequently increasing adherence to treatment. In light of the high frequency of depressive disorders associated with stigma/internalised stigma in young people with perinatal HIV infection, it is advisable to put available effective diagnostic methods and tools (scales, questionnaires) in the daily clinical practice of infectious disease physicians and paediatricians for early detection of mental disorders.

66-72 87
Abstract

Antiretroviral therapy is a treatment that involves the regular use of a combination of antiviral drugs. During pregnancy, women with human immunodeficiency virus (HIV) do not stop antiretroviral treatment, as this is necessary to reduce the risk of HIV transmission from the mother to the fetus. However, the body of a pregnant woman can affect the way the antiretroviral medications work, called their pharmacokinetics and pharmacodynamics. This can increase the risk of adverse drug reactions (ADR) from the medications.

The aim of the study was investigated of the frequency of ADR of antiretroviral therapies based on analysis of spontaneous reports of ADR among pregnant women who were registered in the ARCADe regional database (Adverse Reactions in Crimea, Autonomous Database). 

Materials and methods. The study included 64 spontaneous ADR reports registered in the electronic database of spontaneous ARCADE messages in the Republic of Crimea between January 1, 2012 and December 31, 2021. These reports were collected from pregnant women who were taking ARP.

Results and discussion. The most common types of ADR have been reported when using combined antiretroviral medications and nucleoside reverse transcriptase inhibitor drugs. The combination of lamivudine and zidovudine drugs was the most frequent cause of adverse effects among pregnant women on antiretroviral therapy. Hematopoietic disorders and dyspepsia were the most prevalent clinical manifestations of the ADR. Almost 85% of identified ADR required medication adjustment, although only 5% were classified as severe manifestations of the events.

Conclusion. Long-term antiretroviral drug use requires regular monitoring of ADR, particularly during pregnancy, to provide timely care and maintain high levels of patient adherence to an effective antiretroviral treatment regimen. Despite the high incidence of anemia, skin, and dyspeptic problems, the proportion of serious ADR was found to be relatively low, which justifies the use of antiretroviral therapy during pregnancy. This justifies the continued use of antiretroviral therapy during pregnancy, as it has undeniable benefits in preventing transmission of HIV from mother to child, suppressing viral replication, and reducing mortality in infants.

73-80 120
Abstract

Military personnel constitute a separate cohort of the population with characteristic features of the spread and course of HIV infection associated with military life, the nature and physiology of military labor. At the same time, it is assumed that more than 2.2% of the male population of mobilization age in Russia are HIV affected.

The aim: analysis and generalization of the experience of the infectious diseases clinic of the Military Medical Academy in prescribing antiretroviral therapy.

Material and methods included all case histories of patients who were hospitalized in the clinic from March 2022 to September 2024 with a diagnosis of HIV infection (n=107). At the second stage of the study, cases requiring antiretroviral therapy were selected (n=42).

Results and discussion. 88% of patients were in the stage of secondary diseases of HIV infection. Severe immunodeficiency according to the classification of immune disorders of the World Health Organization was determined in 83,3%. The average CD4+ lymphocyte level was 151±49 cells/μl (11.3±2.9%). The most frequently prescribed antiretroviral therapy regimen was a combination of lamivudine, tenofovir and dolutegravir.

Conclusion. A distinctive feature of military medical organizations is the inclusion of infectious disease departments as structural units, which distinguishes them from civilian multidisciplinary hospitals in terms of patient’ integrated management. It has become possible to simultaneously provide medical care to polymorbid patients by a multidisciplinary team in the conditions of a single medical organization. The experience of departmental medicine can be useful in providing high-quality medical care to the civilian population.

81-89 100
Abstract

The aim. To identify the medical and social features of respiratory tuberculosis in newly diagnosed patients in combination with HIV infection.

Materials and methods. For the analysis, information was used on 1,234 newly diagnosed patients with verified respiratory tuberculosis with or without HIV infection during two follow-up periods (from January 2017 to March 2019 and from November 2019 to December 2021).

Objectives of the study. To conduct a dynamic analysis of clinical and epidemiological data of patients with newly diagnosed respiratory tuberculosis and HIV infection; to determine the level of multiple drug resistance of MBT to anti-tuberculosis drugs.

Results and discussion. A newly diagnosed patient with HIV-associated tuberculosis living in an area with a high prevalence of HIV (Tomsk region) is mainly an urban resident, a young man aged 18–40 years, with an HIV infection history of 3 or more years, not registered for HIV in a quarter of cases, and with severe immunodeficiency in 60% of cases. During the observation period, the proportion of patients with a CD4 lymphocyte level below 200 cells/ml increases (53.3% and 60.9%, respectively, p=0.07), and as a pathogenetic result of severe immunodeficiency, the proportion of patients with disseminated pulmonary tuberculosis increases proportionally (49.8% and 63.8%, respectively, p=0.001); primary multiple drug resistance of the pathogen reaches a frequency of occurrence of 43.1% in TB/HIV, and 23.8% in patients without HIV infection (p<0.001).

Conclusion. First identified tuberculosis in HIV-infected patients in the region with high prevalence of HIV (Tomsk region) is characterised by an advanced severe course with a high frequency of MDR MBT without dynamic improvement.

90-98 117
Abstract

The aim: to determine the main risk factors and their impact on the development of tuberculous enterocolitis (TEC) in Moscow. Materials and methods. Risk factors for the development of intestinal tuberculosis were studied in 217 adult patients with a combination of respiratory tuberculosis and intestinal tuberculosis compared with 22 663 adult patients with respiratory tuberculosis without tuberculosis intestines registered in 2016–2023.

Results and discussion. As a result of the calculations, the main risk factors for the development of tuberculous enterocolitis were immunosuppressive therapy (aOR 12.05; 95% CI 6.71–20.69), diabetes mellitus (aOR 9.06; 95% CI 4.45–16.81) and HIV infection (aOR 7.55; 95% CI 5,40–10,67). In our study, we were able to identify the main risk factors affecting the development of tuberculous enterocolitis and adapt the results obtained to the diagnostic search scheme in patients with generalized tuberculosis: the examination algorithm for such patients must necessarily include performing an abdominal CT scan with double contrast enhancement and colonoscopy with biopsy.

Conclusion. Taking into account predictors of tuberculous enterocolitis and including them in clinical diagnostic algorithms can help in early diagnosis of the disease and avoid the appearance of its complicated forms.

99-106 110
Abstract

The aim: to describe the duration of SARS-CoV-2 virus shedding in patients with HIV infection and to identify factors associated with prolonged viral shedding.

Materials and methods: in a prospective study, the clinical and laboratory characteristics of COVID-19 and HIV infection and the duration of SARS-CoV-2 virus shedding were compared in 170 patients, titers of virus neutralizing antibodies to SARSCoV-2 were identified in 68 patients; pathogen genotyping was performed in 36 patients. Statistical analysis was carried out using the IBM SPSS Statistics package.

Results and discussion: there were no significant differences in the duration of SARS-CoV-2 virus shedding in patients with varying severity grade of COVID-19; a negative relationship between the titer of virus neutralizing antibodies to SARS-CoV-2 and viral shedding duration was revealed. In 35.9% of patients (61 persons), the persistence of the virus lasted for more than 21 days, this group was characterized by an unfavorable course of HIV infection in the absence of ART, significantly lower CD4 cell values and a higher HIV viral load in the blood. Virus shedding was shown to be significantly longer in patients with B.1.1 strain versus other SARS-CoV-2 gene variants. Mutations in the Spike protein gene that increase the infectious ability of the pathogen and reduce its sensitivity to neutralizing antibodies were found in 4 patients.

Conclusion: the severity of COVID-19 did not affect the duration of SARS-CoV-2 virus shedding in patients with HIV infection. Long-term persistence of the virus was discovered in patients with severe immunodeficiency (CD4<200 cl/μl) in the absence of ART. Patients with prolonged viral shedding pose an epidemiological risk in regard to developing new mutational variants of the pathogen.

EPIDEMIOLOGY

107-116 154
Abstract

Aim: to assess the epidemiological manifestations of HIV infection on the territory of the Siberian Federal District of the Russian Federation.

Materials and methods. The study was conducted in 10 territories of the Siberian Federal District over a fourteen-year period of HIV infection surveillance (2009–2022). The material for the study was information from federal statistical observation forms No. 2, No. 61, No. 4, as well as departmental observation «Information on measures for the prevention of HIV infection, hepatitis B and C, identification and treatment of patients with HIV infection.» A traditional descriptive evaluative observational epidemiological study algorithm was used.

Results and discussion. In the Siberian Federal District, the long-term average incidence of HIV infection was 101.2 per 100 thousand population (95% CI 101.0–101.4), which is 2 times higher than the Russian average of 48.3 (95% CI 48.3–48.4). The incidence of morbidity among children decreased from 9.6 cases to 4.3 cases per 100 thousand children (Tdecr.=–4.0%, p=0.009). There was an increase in the proportion of the female population among the sick from 35.5% in 2009. up to 46.5% in 2022. The incidence of women in the age group of 15–17 years was 3.7 times higher than the incidence of men, in the age group of 18–24 years it was 1.8 times. The highest incidence rate was observed in three subjects of the Siberian Federal District — Kemerovo, Irkutsk, and Novosibirsk regions. 50.6% of patients had a subclinical stage, 49.1% — stages of secondary diseases. In the Siberian Federal District, during the studied period, the coverage of the population with HIV testing increased by 1.7 times and amounted to 32.4% of the population; the coverage of antiretroviral therapy for HIV-infected patients who were under dispensary observation increased to 90.1%; it decreased by more than 2 times number of cases of treatment interruption.

Conclusion. Despite the observed trend towards a decrease in the incidence rate of the population, the relevance of the problem of HIV infection for the health care of the region remains, which requires the introduction of additional measures aimed at stabilizing the epidemiological situation.

117-127 95
Abstract

The aim of the study was to determine characteristics of COVID-19 epidemic process in the Volga federal district in 2020–2023.

Materials and methods. Analysis of the COVID-19 epidemic process progress was carried out from March 30, 2020 to December 31, 2023. We used information from the website «report.gsen.ru», materials from the national platform for the aggregation of SARS-CoV-2 genome data — VGARus, the official website of Rospotrebnadzor, the information portal Stopcoronavirus rf, data from the official World Health Organization (WHO) website, weekly reports submitted by the Rospotrebnadzor of the subjects of the Volga Federal District.

Results and discussion. The average district incidence rate of a new coronavirus infection was 1280.70/0000 in 2020, 3863.00/0000 in 2021, 7352.20/0000 in 2022, 1398.30/0000 in 2023. In the period from 2020 to 2023, the prevalence of persons aged 30–49 years and 50–64 years in the structure of COVID-19 cases was recorded. The largest proportion of severe cases was recorded in 2022 and 2023 (58.8% and 57.9%, respectively), the smallest — in 2020 (37.6%). The average district mortality and lethality rates were — 20.60/0000 and 1.6% in 2020, 150.80/0000 and 3.9% in 2022, 46.90/0000 and 0.6% in 2022, 3.00/0000 and 0.2% in 2023 respectively.

Conclusion. In the period 2020–2023, the COVID-19 incidence rate in general in the Volga Federal District varied, there was an increase in the proportion of mild severe cases, as well as a decrease in mortality and lethality rates, which is associated with a change in circulatingSARS-CoV-2 genovariants, the formation of population immunity, and the organization of a comprehensive system of anti-epidemic measures.



Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2077-9828 (Print)