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HIV Infection and Immunosuppressive Disorders

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Vol 16, No 2 (2024)
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https://doi.org/10.22328/2077-9828-2024-16-2

EDITORIAL

7-22 343
Abstract

The aim. This study aimed to review literature on the topic of «Low-level viremia (LLV) in HIV infection» to systematically organize data under various themes, including «definitions», «mechanisms», «causes», «risks», «clinical implications», «prevention», and «management».

Materials and methods. A comprehensive search of literature data was conducted to gather information on LLV in HIV infection. The collected data were categorized into themes based on the aforementioned topics.

Results and discussion. The study involved the systematic organization of data on low viremia, including its sources and potential mechanisms. Detailed discussions were held on questions surrounding HIV sanctuaries, clonal expansion, and their role in LLV formation. Additionally, the contribution of factors such as adherence, drug resistance, and drug interactions to LLV incidence was assessed. Furthermore, an algorithm of actions to prevent and address LLV, based on expert opinions, was developed.

Conclusion. The LLV phenomenon is under active investigation, with an evolving understanding of its sources and formation mechanisms. Based on this knowledge, future recommendations for practitioners are anticipated, aimed at achieving effective virological responses in all HIV-infected patients.

LECTURE

23-39 202
Abstract

The lecture outlines modern ideas about the etiology, features of the epidemic process, mechanisms of damage to the human body, clinical manifestations, diagnosis, treatment and prevention of infection caused by the Nipah virus. Particular attention is paid to the characteristics of individual outbreaks of the infectious process in various geographical regions of the world, early and long-term psychopathological, neurological and cognitive consequences due to human infection with the Nipah virus. The risk factors for the emergence and rapid spread of infection with a very high mortality rate, reaching 100%, are emphasized, which determines the high pandemic potential and hidden threats to human society. Recommendations are outlined for the prevention of transmission of infection caused by the Nipah virus at all levels: from animals to humans, from humans to humans, in medical institutions, which, in the absence of effective vaccine prevention and specific antiviral treatment, are the basis for containing the spread of the infectious process. In this regard, measures taken and planned to provide patients and contact persons with adequate medical and psychological care, features of the development and implementation of effective anti-epidemic, clinical diagnostic algorithms, timely and high-quality social and hygienic monitoring of environmental objects against the backdrop of increasing biological threats from outside, and within the country will minimize the risks of biological threats. The lecture is intended for doctors of various specialties, including infectious disease specialists, epidemiologists, general practitioners, neurologists, psychiatrists, laboratory diagnosticians, radiologists etc.

ORIGINAL STUDIES

40-50 189
Abstract

The aim of the study: to compare the genetic diversity of the Vpu protein in HIV-1 in the people living with HIV (PLWH) with different stages of the disease.

Materials and methods. An analysis was carried out of 259 clinical samples of whole blood from HIV-infected patients with no experience of taking antiretroviral therapy, who were observed at the Center for the Prevention and Control of AIDS and Infectious Diseases, Moscow, Russia. The analysis included the following stages: extraction of proviral DNA, amplification of the region of the virus genome containing the vpu gene, sequencing of amplification products, genotyping, comparison of conservation and amino acid substitutions in the Vpu protein sequences in PLWH with different stages of the disease.

Results and discussion. In 255 out of 259 (98.4%) clinical samples, a sub-subtype A6 virus variant was identified. The consensus sequence of the Vpu sub-subtype A6 protein was obtained, which contained 81 amino acids. No significant differences in the conservation of Vpu protein sequences were found between HIV-1 variants obtained from patients with different stages of the disease. Amino acid substitution P3A was significantly more common in PLWH with the second stage of HIV infection.

Conclusion. The results obtained highlight the issue of the influence of non-structural proteins of HIV-1 on the course of the disease and indicate directions for possible research in the future.

51-59 179
Abstract

The aim of this study was to evaluate TREC and KREC levels in HIV-infected individuals.

Materials and methods. The study material was whole blood samples obtained from HIV-infected individuals with less than one year of infection (n=50) and long-term patients with high viral load and virological failure of ART (n=50). The obtained data were analyzed in comparison with the norm values established earlier for adults of different age groups. Multicolour flow cytometry was used to phenotype peripheral blood cells of HIV-infected individuals. To assess the levels of TREC and KREC molecules with all total DNA samples, quantitative multiplex Real-time PCR was performed using the reagent kit

«TREC/KREC-AMP PS» (Saint-Petersburg Pasteur Institute, St. Petersburg), according to the manufacturer’s instructions. Results and discussion. A reliable direct correlation TREC levels in peripheral blood with the number of CD45+CD3+CD19– T-cells (r=0.77, p<0.0001), KREC levels with the number of CD45+CD3–CD19+ B-cells (r=0.79, p<0.0001) was determined. A significant decrease in the levels of TREC and KREC molecules in HIV-infected individuals with high viral load and virological failure of antiretroviral therapy was shown (AUC=0.99, Se=0.99, Sp=0.99 for TREC and for KREC).

Conclusion. Assessment TREC and KREC molecule levels in peripheral blood can be used to detect abnormalities in the functioning Tand B-cell immunity to monitor the ART effectiveness in HIV-infected individuals.

60-68 174
Abstract

The aim. To study the features of the clinical course of a new coronavirus infection in patients infected with HIV.

Materials and methods. The study included patients with HIV infection who received inpatient care for a new coronavirus infection (n=118). The diagnosis of U07.1 was made by detecting SARS-CoV-2 RNA. The diagnosis of U07.2 was made on the basis of epidemiological and clinical data in the presence of antibodies to SARS-CoV-2 in the blood.

Results and discussion. The overall cohort of patients was dominated by women (55,9%), the average age of all co-infected patients was 37,5±2,78 years. The study was dominated by patients with a long history of HIV infection (66,1%), 43,2% received antiretroviral therapy (ART). The new coronavirus infection had a moderate course in 75,4% of patients. Severe form was recorded in 16,9% of patients. The mortality rate was 12,7%. The clinical picture of the new coronavirus infection upon admission was very variable due to comorbid pathology. The most frequently recorded symptoms upon admission were: increased body temperature (100%); weakness and increased fatigue (94,8%); cough (83,9%); shortness of breath (75,4%). Less frequently recorded: rhinorrhea (54,2%); sore throat (44,1%); gastrointestinal syndrome (21,2%); cerebral syndrome (17,8%); edematous-ascitic syndrome (13,5%); hepatolienal syndrome (13,5%); exanthema syndrome (10,2%). In 28,7% of patients, the number of CD4 lymphocytes was less than 200 cells/ml. The average level of CD4 lymphocytes was 321,3±43,6 cells/ml. The work revealed that as the degree of immunosuppression increased, there was a sharp increase in cases of severe forms of the new coronavirus infection, as well as an increase in deaths. The average HIV RNA level was 578 161,9±103 457,4 copecks/ml. A high HIV viral load (more than 100 000 cop/ml) was observed in 41,5% of cases, and only in this group of patients were severe forms of the new coronavirus infection recorded and, as a consequence, death. All observed patients had comorbid pathology in the form of opportunistic infections and/or concomitant diseases. The most frequently recorded opportunistic infections were: candidiasis (77,9%), cerebral toxoplasmosis (17,8%), Pneumocystis pneumonia (16,1%), tuberculosis (14,4%), central nervous system damage caused by the Epstein-Barr virus (10,2%), cytomegalovirus infection (6,78%), HIV-associated anemia (3,39%), cervical cancer (1,69%). Often opportunistic infections had a polyetiological cause. Of the concomitant diseases, bacterial pneumonia (66,9%), chronic viral hepatitis (40,7%), cardiovascular diseases (26,3%), diseases of the gastrointestinal tract (21,2%), and nervous system were most often recorded (5,93%), urinary system (5,08%) and cancer (5,03%). In 89,8% of coinfected patients, prolonged release of SARS-CoV-2 was observed, which affected the duration of antiviral therapy and the length of hospitalization.

Conclusion. The new coronavirus infection and HIV infection are the intersection of two epidemics with the subsequent mutually aggravating effect of pathogens on each other. Among the co-infected patients, young people of working age, reproductive age (30–49 years) with a long history of HIV infection (66,1%) and not taking ART (56,3%) predominated. The new coronavirus infection in HIV-infected patients more often occurred in a moderate form (75,4%), pneumonia was recorded in 83,1%. A severe form of the new coronavirus infection was recorded in 16,9% of patients. The work shows that as the degree of immunosuppression increased, there was a sharp increase in the frequency of severe forms of the new coronavirus infection. In the general cohort of patients, comorbid pathology was recorded in the form of opportunistic infections and/or concomitant diseases. Often opportunistic infections had a polyetiological cause. Multimorbidity aggravated the condition of patients and largely increased the risk of an unfavorable outcome. Mortality in the group of coinfected patients was 12,7%.

69-77 146
Abstract

The aim of the study was to identify the indicators that are most significant for predicting the features of the course of COVID-19 in hospitalized patients.

Materials and methods. 250 case histories of patients aged 18 to 86 years with COVID-19 hospitalized in the hospital of the city of Nukus, Republic of Uzbekistan, redesigned to provide care to patients with COVID-19 from July 1, 2020 to March 2022, were analyzed. Patients who had a wave–like course of the disease with the development of complications, an increase in the volume of lung damage, were included in the main group (62 patients, 3 of whom were extremely severe). The patients who had stable positive dynamics (188 people) formed a comparison group.

Results and discussion. Among patients over 65 years of age, 36% had a complicated course, in the 45–65 age group — 29% (p>0.05), and among patients under 45 years of age — 13% (p<0.05). The main group was dominated by men (79%). Among hospitalized villagers, an increase in the severity of the condition was noted in 30% of cases, and among patients from the city of Nukus, such patients were 20% (p<0.05). The highest values of D-dimer, interleukin-6 and C-reactive protein were in both groups, significant differences between the groups were revealed in the levels of D-dimer and interleukin-6. Significant differences between the groups were found in the levels of D-dimer, interleukin-6, ferritin, ALT, AST, and urea.

Conclusion. COVID-19 has become one of the most studied diseases to date, but aspects of the course of this disease in certain population groups are still not sufficiently investigated. The complicated, progressive course of COVID-19, according to the results of our study, was recorded in all age groups of the adult population, more often in men from rural areas aged over 45 years with chronic diseases. The main prognostic markers of the complicated and progressive course of COVID-19 should be considered high levels of D-dimer, interleukin-6 and ferritin.

78-84 162
Abstract

The aim. To study the association of polymorphic variants of the GSTM1 (E/D) and TNF-s (308G>A (rs1800629) genes with the formation of decay cavity sizes in patients with pulmonary tuberculosis.

Material and methods. The study group is represented by 335 patients suffering from pulmonary tuberculosis (212 people were diagnosed with pulmonary tuberculosis for the first time; 123 people with chronic pulmonary tuberculosis) aged 18 to 65  years; receiving an intensive phase of chemotherapy. To conduct molecular genetic studies; 335 people had whole blood taken from a vein into a test tube with EDTA. Genomic DNA was isolated using Arrow Blood DNA 500 reagent kits from whole blood (at the NorDiag Arrow station). After; the polymerase chain reaction was staged in real time using sets of reagents for genotyping SNPs: GSTM1 (E/D) and TNF-s (–308G>A (rs1800629).

Results and discussion. In patients with pulmonary tuberculosis; the genotype DD of the gene GSTM1 (E/D) and the genotype GG of the gene TNF-s –308G>A (rs1800629) is most often associated with the formation of the size of decay cavities.

Conclusion. It is advisable to introduce genotyping of the GSTM1 and TNF-s genes into the practice of a phthisiologist in order to predict the probability of the formation of the size of decay cavities in patients with pulmonary tuberculosis.

 

85-93 148
Abstract

In this study, a comprehensive instrumental assessment of the autonomic status of tuberculosis patients and those with concomitant HIV infection at the beginning and during treatment was conducted, revealing the structure of dysfunction through heart rate variability analysis. Correcting the identified disorders will enhance the effectiveness of treatment through a comprehensive individualized approach.

The aim of the study: to assess the autonomic status of patients with tuberculosis and concomitant HIV infection during the course of treatment using spectral analysis of heart rate variability and to determine its clinical significance.

Materials and methods. The study involved 195 participants. They were divided into two groups: a control group of 70 healthy individuals and an observation group of 125 newly diagnosed patients with infiltrative and disseminated pulmonary tuberculosis, further divided into two subgroups. The first subgroup included 64 patients with pulmonary tuberculosis, and the second subgroup included 61 patients with tuberculosis combined with HIV infection. The structure of the autonomic nervous system was studied using the computer complex «Varicard 2.51» for processing variocardiograms and analyzing heart rate variability (Registration certificate for medical device dated 10.12.2007 No. FSR 2007/01390). All patients were examined under identical conditions. Calculations were performed using SPSS Statistics v. 23.

Results and discussion. The data on the assessment of the state and dynamics of the total power spectrum of RR intervals (TP) in the control group and in patients with tuberculosis and concomitant HIV infection in subgroups 1 and 2 of the observation group during treatment are presented. When comparing the frequency of TP above the «normal zone» in the control group and subgroup 1 of the observation group (t1= 3.30; p1<0.01; t2=1.70; p2>0.05), in the control group and subgroup 2 of the observation group (t1=3.51; p1<0.01; t2=2.64; p2<0.01), statistically significant differences were found in subgroup 1 before treatment and in subgroup 2 before and after treatment. The significant decrease in TP levels above the «normal zone» in patients of subgroups 1 and 2 before treatment indicated significant mobilization of the body’s regulatory system reserves needed to maintain vital functions. By the end of the hospital treatment stage, TP levels had not recovered in patients of subgroup 2, marking more pronounced regulatory disturbances in patients with pulmonary tuberculosis combined with HIV infection.

Conclusion. The assessment of the state of regulatory systems and the body’s reserves based on heart rate variability indicators showed that in healthy individuals, these systems were at levels ensuring the body’s normal homeostatic balance with the regulatory systems functioning normally without excessive stress and high resource mobilization. In patients with pulmonary tuberculosis, the state of regulatory systems was at a lower level, especially in patients with concomitant HIV infection.

94-99 145
Abstract

Opportunistic infections account for more than 90% of all deaths associated with immunosuppression resulting from exposure to the human immunodeficiency virus  (HIV). Fatal opportunistic infections  include Pneumocystis pneumonia, cryptococcosis, cytomegalovirus infection, and viral hepatitis B and/or C. HIV-infected pregnant women have a high incidence of cytomegalovirus infection, which increases the risk of transplacental transmission of HIV from mother to fetus. In addition, an important factor in perinatal transmission of HIV is a genital infection caused by herpes simplex virus type 2 detected during pregnancy in HIV-infected women. Also, at present, there is no doubt about the possibility of damage to placental cells by the SARS-CoV-2 virus and its transplacental transmission.

The aim of this study was to study the morphological features of the placenta in the presence of opportunistic infections caused by viruses of the herpes family (herpes simplex viruses types 1/2, cytomegalovirus, Epstein-Barr virus), as well as SARS-CoV2 in HIV-infected pregnant women.

Materials and methods. A study was conducted of 21 placentas with various pregnancy outcomes in HIV-infected women, including 12 placentas obtained as a result of term birth, 1 placenta from premature birth at 29 weeks, and 8 observations of failed miscarriages (non-developing pregnancy).

Results and discussion. Viral lesions were represented by the action of HIV with giant cell metamorphosis of trophoblast cells and placental macrophages, as well as infiltration by immunocompetent cells and fibrosis of the villous stroma. In addition, groups of immature villi were identified, the edematous stroma of which contained an increased number of large cells with light nuclei. In HIV-infected pregnant women with immunosuppression, the outcome of pregnancy in 8 cases was a miscarriage with a morphologically detected and immunohistochemically confirmed infection caused by herpes simplex virus types 1/2 (3 observations), cytomegalovirus (2 observations), and SARS-CoV-2 (3 observations), in 1 case the outcome of pregnancy was premature birth with morphologically identified and immunohistochemically confirmed infection caused by the Epstein-Barr virus.

Conclusion. The placentas of HIV-infected pregnant women are characterized by impaired villous maturation with stromal fibrosis, which is the morphological substrate of chronic placental insufficiency with varying degrees of compensation. If HIVinfected pregnant women have opportunistic infections caused by viruses of the herpes family (herpes simplex viruses types 1/2, cytomegalovirus, Epstein-Barr virus), as well as SARS-CoV-2, pronounced involutive-dystrophic changes are observed in the placentas — perivillous deposition fibrinoid, petrification, which increases the likelihood of an unfavorable pregnancy outcome in the form of miscarriage or premature birth.

100-105 497
Abstract

Despite advances in antiretroviral therapy (ART), diarrhea is common among people living with HIV (PLHIV) and negatively impacts quality of life. Although diarrheal diseases caused by opportunistic infections have decreased in the ART era, the overall prevalence of diarrhea remains unchanged, estimated at 28% to 60% of PLHIV.

The aim of the study: to conduct a comparative assessment of the clinical efficacy of enterosorbents in the treatment of diarrheal syndrome in children with HIV infection.

Materials and methods. The study material included 80 HIV-infected children who experienced acute infectious diarrhea aged 5 to 14 years. The main group included 40 children who received enterosgel, 2 times 1 tablespoon included in the traditional treatment regimen, and the control group included 40 children who received the drug lactofiltrum against the background of traditional therapy, 1 tablet 3 times a day. The duration of treatment was 10 days.

Results and discussion. During the treatment of acute diarrhea in children with HIV infection with Enterosgel, a significant decrease in the daily amount and in the duration of diarrhea was observed, which leads to a noticeable loss of signs of dehydration (P<0.05). Elimination of acute diarrhea in children with HIV infection may also have eliminated the underlying intoxication syndrome due to the underlying and burning disease, which may lead to a reduction in health care costs and socioeconomic burden.

Conclusion. During the treatment of acute diarrhea in children with HIV infection with Enterosgel, a decrease in the daily amount and in the duration of diarrhea is reliably observed, which leads to a significant disappearance of signs of dehydration (р<0.05).

EPIDEMIOLOGY

106-117 279
Abstract

The aim of the study: to assess the genetic diversity of HIV-1 variants circulating in St. Petersburg.

Materials and methods. The study included 289 patients with virological ART failure in 2022 in the St. Petersburg AIDS Center. Fragments of the pol gene encoding integrase, reverse transcriptase and protease were analyzed by polymerase chain reaction and Sanger sequencing. Phylogenetic tree created by the Neighbor-joining method with 1000 repeats of nucleotide sequences, bootstrap values >70. To assess the circulation of HIV genovariants in dynamics in St. Petersburg, sequences and clinical and laboratory parameters obtained from 544 patients since 2018. The total sample included 833 samples (289 were collected in 2022), compared with the results of a study from 1104 HIV-infected patients in 2006–2011.

Results and discussion. Monovariants of HIV dominated in the examined patients (95.1%, 275 people), subtype A6 — 88.2% (255 people); subtype B — 5.9% (17 people); C — 0.3% (1 person); G — 0.7% (2 people), the proportion of recombinant forms — 4.9% (14 people). In the sample collection, the proportion of new HIV cases of non-A subtype was 13.3% in 2006–2011, and 11.1% in 2018–2022. A significant increase in the incidence of recombinant forms of HIV-1 was revealed from 1.6% to 3.5% (c2=6.111; p=0.014). In the group (2018–2022), the recombinant form of CRF63_02A6 was more common (15/29 people).

Conclusion. Phylogenetic analyses makes it possible to determine HIV subtypes, but also to establish the potential geographical origin of the virus, to identify transmission clusters taking into account the socio-demographic indicators of HIV-infected patients. Molecular epidemiological monitoring can be used to develop and implement programs to counter the spread of HIV among the population. The dominant genetic variant of HIV circulating in St. Petersburg is sub-subtype A6, as it was 10 years ago. The proportion of new cases of infection with non-A subtype of HIV remains stable, with a downward trend. The increase in the frequency of detection of recombinant forms of HIV-1 is probably related to the migration processes of the population.

LEGAL ISSUES

118-127 235
Abstract

In Russia, cases of HIV transmission related to medical care are registered annually, including cases related to hemotransfusion. A clinical case of an artificial coinfection with human immunodeficiency and hepatitis C viruses in the course of medical care, as well as its clinical, social, legal and economic consequences, is presented. This clinical case is noteworthy for its relevance from both the perspective of examining the clinical course and treatment of illnesses, as well as analyzing the medical and legal implications of a iatrogenically acquired infection. The recurrence of such incidents of infection with significant social diseases in the 1990s and 2000s necessitated a serious reorganization of the national blood transfusion system and blood components. At present, with strict adherence to legal requirements in place, the risk of infection has been minimized.



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ISSN 2077-9828 (Print)