Introduction. Since the appearance of the immune deficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) at the beginning of 1980s, humanity started to understand elementary processes, underlying biology of HIV that enabled to develop safe and efficient treatment methods. Currently HIV therapy includes combined treatment regimen that allows combined drug interaction.

Objective. To study the features of pharmacokinetics and pharmacodynamics, and also drug interaction of specific product groups, affecting human immunodeficiency virus.

Materials and methods. Analytical review is based on analysis of literary sources of scientific database (PubMed, Cochrane Library, Сyberleninka) that contains information about peculiarities of pharmacokinetic and pharmacodynamic antiretroviral products’ interaction (ARVP) when used by HIV-infected patients for the period 1995–2022. 

Results and discussion. The current study enabled to summarize the research results, devoted to the issue of combined ARVP use by HIV-infected patients, and also to identify variants of irrational ARVP combination, caused by increased risk of toxicity with their simultaneous application.

Conclusion. Studying the characteristics of each medical product, used in HIV infection therapy, allows to choose optimal pharmacotherapy regimens, taking into account individual patient characteristics, and also to predict and prevent the risk of adverse reactions in the future.

Objective. To study the epidemiological, medical, social and clinical factors that affect the manifestations and treatment of diseases — infections caused by the immunodeficiency virus (HIV) and the new coronavirus (SARS-CoV-2), which underlie the formation of a personalized approach to the management and treatment of people living with HIV (PLHIV).

Materials and methods. Epidemiological analysis of morbidity and mortality from COVID-19 in the Leningrad region for 2021–2022 was carried out. The research team conducted a questionnaire and analysis of medical documentation of 122 HIVpositive patients registered at the Leningrad Regional Center for the Prevention and Control of AIDS and Infectious Diseases who suffered a novel coronavirus infection (COVID-19) in the period from 2020 to 2022. An assessment was made of the psychological and social characteristics of patients affecting adherence to antiretroviral therapy (ART), the clinical picture of the course of HIV infection, including in combination with COVID-19. The fact of SARS-CoV-2 disease was confirmed by polymerase chain reaction (PCR) smears from the mouth and nasopharynx. Additionally, a group of 59 PLHIV hospitalized in hospitals in St. Petersburg and the Leningrad region with a severe form of COVID-19 was isolated for analysis.

Results and discussion. Number of COVID-19 cases in 2020–2021 in the Leningrad region amounted to 15.553 people, of which 1.553 had a history of HIV infection (13.5% of patients registered at the dispensary). The mortality rate among PLHIV who underwent COVID-19 was 5.1%. An equal ratio of women and men was observed among 122 surveyed patients, the average age of respondents was 41 years. When assessing the social status of the respondents, it was found that 25.4% had higher education, 56.5% had specialized secondary education. 72.9% had a permanent job. 61.4% of respondents considered themselves to be in the category of material well-being of «average level», 24.6% — to «below average». The sexual route of HIV infection was established in 50.8% of patients, injectable was 29.5%, in other cases it was not unknown. The average level of CD4 lymphocytes in the blood was 544 cl/mcl, most patients (90.2%) had an undetectable indicator of HIV viral load (VL). The average duration of the disease with the new coronavirus in HIV patients was 15.6 days. At the same time, 108 (88.5%) people noted a mild course of COVID-19 and did not need hospitalization. Coverage of COVID-19 vaccination among the surveyed PLHIV was 40.9%. According to data from 59 case histories of PLHIV hospitalized as a result of the severe course of COVID-19, 55 people died, a pathoanatomic autopsy was performed in 26 cases. The autopsy revealed the following complications and concomitant diseases: miliary tuberculosis (7.7%), purulent endocarditis (11.5%), sepsis (19.2%). Improvement in the dynamics was observed only in 4 PLHIV, whose further fate is unknown.

Conclusion. The study showed that the incidence of SARS-CoV-2 among PLHIV in the Leningrad region is comparable to the general population, however, the total mortality among HIV-infected patients is higher than in the region and across the country. As a result of the analysis, we came to the conclusion that HIV infection and COVID-19 are independent in terms of co-infection at the outpatient stage. The exception is severe and aggravated comorbid cases, which required a more detailed assessment of the condition, the involvement of a larger number of specialists, as well as laboratory and instrumental research methods. The results obtained determined the need for a comprehensive interdisciplinary approach to patients with HIV infection, taking into account their personal needs. Medical personnel providing care to PLHIV should take into account not only the clinical picture of the disease, but also the psychosocial status of the patient, in order to improve the outcomes of COVID-19 and HIV infection.

Objective. To develop prognostic criteria for the chronic course of cytomegalovirus infection by studying disorders of the regulation of the immune response in children of the first year of life against the background of hypoxic-ischemic CNS damage.

Materials and methods. 108 newborns with cytomegalovirus infection occurring against the background of perinatal hypoxicischemic lesions of the central unequal system were examined. All observed patients at 1 and 3 months of life conducted an immunological examination, including the determination of T and B-lymphocytes. Determination of the population and subpopulation composition of peripheral blood lymphocytes, activation markers was carried out by the method of one- and twoparameter phenotyping using reagents from Immunotex (France), FITC (fluorescein isothiocynate) — labeled with CD3⁺, CD4⁺, CD8⁺, CD20⁺ and PE (phycoerythrin) — labeled CD28⁺, CD40⁺. The results were recorded on a BECKMAN COULTER EPICSXL-II flow cytometer (USA) using standard protocols. The observation groups consisted of 78 children (72.2%) with an acute course of the disease (Group 1) and 30 children (27.3%) with a chronic course (Group 2).

Results. Of the totality of the studied parameters of the cellular and humoral parts of the immune system, statistically significant for the prognosis of the chronic course of cytomegalovirus infection in children of the first year of life against the background of hypoxic-ischemic CNS damage were found: CD8, CD40, CD3⁺CD28⁺, CD20⁺CD40⁺. Using the PolyAnalist 3.5 Pro CNS package, systems of inequalities were obtained and a formula for predicting the chronic course of cytomegalovirus infection in children in the first year against the background of perinatal hypoxic-ischemic CNS damage was calculated.

Conclusion. A statistically significant relationship was found between the prognosis of the chronic course of cytomegalovirus infection against the background of perinatal hypoxic-ischemic CNS damage and the level of CD20, CD4, costimulatory molecules CD3⁺CD28^–, CD20⁺CD40⁺. The proposed diagnostic rules can be considered screening markers for the prognosis of the chronic course of cytomegalovirus infection against the background of perinatal hypoxic-ischemic CNS damage in newborns, which makes it possible to start specific therapy in a timely manner.

Objective. To establish a probable source of infection using phylogenetic analysis in the investigation of cases of HIV infection. 

Materials and methods. HIV genome sequencing was carried out using the kit ViroSeq (Celera). The phylogenetic tree was constructed using the maximum likelihood method in the Mega 6 program. As a comparison group, 40 samples of HIV-infected patients from the Krasnoyarsk region were used, as well as 25 nucleotide sequences of various HIV subtypes taken from the international GenBank database. The reliability of the resulting tree was evaluated in bootstrap analysis, a branch rotation test for a thousand random constructions.

Results and discussion. The paper presents five cases of epidemiological investigations with a probable nosocomial and occupational mechanism of HIV infection transmission in the Krasnoyarsk region. In 2013, a study was conducted on the infection of three persons treated in the same hospital with an HIV-infected patient. A close genetic relationship of HIV was shown in newly identified individuals, the probable source could not be examined due to death. Second epidemiological investigation in 2013. The association of cases of infection between a newly diagnosed woman with HIV infection and a patient with a previously established HIV status is shown. Both persons were simultaneously in the same medical institution. To determine the direction of transmission of the virus, a test for the duration of infection was used. In 2014, after receiving medical care in four medical organizations, the patient was confirmed to be HIV positive. In all hospitals there were persons with a confirmed diagnosis of HIV infection. Three of them have been examined. The absence of a phylogenetic relationship was confirmed, the fourth died, the material could not be obtained from him. In 2015, a nurse was injured while caring for an HIV-positive patient. Phylogenetic analysis showed a high degree of genetic relationship between these cases of infection. In 2016, after a car accident, two patients were hospitalized in the intensive care unit. After some time, both were diagnosed with HIV infection. Four HIV-infected patients were in intensive care at the same time. Phylogenetic analysis was carried out in two newly identified individuals and one putative source. The association of infections in newly identified patients was shown, the alleged source could not be established.

Conclusion. The use of molecular genetic methods in epidemiological investigations significantly improves the quality and accuracy of deciphering epidemic chains of HIV infection. 

Introduction. The HIV epidemic situation in the Russian Federation remains tense. Low coverage of antiretroviral therapy (ART) contributes to the disease progression in some PLHIV. Many authors point to a high prevalence of different secondary disease combinations.

Objective. Studying the structure of secondary disease combinations in inpatients and identifying features of immunological and virological indicators.

Materials and methods. There was retrospective analysis of 1440 cases of HIV-infected admission in ICU SBHI «ICH № 2» DZM in 2018–2020. The number of CD4+ cells were estimated in 1185 patients, viral load (VL) is defined in 1173 patients.

Statistical analysis is held, using program StatTech v. 2.6.2 (developer — LLC «Statech», Russia).

Results. 18,5% of patients had 1 secondary disease, 75,9% were diagnosed a combination of 2 and more various lesions. 275 different combinations of secondary diseases are recorded: from 50 combinations of 2 secondary lesions to 4 combinations of 7 nosological units. Ме VL in patients with no secondary diseases — 13 303 copies/ml, with 1 secondary disease it increased 3,2 times (42 926) (p<0,001). Similar changes are detected with 3, 5 and 6 diseases. Ме number of CD4+ lymphosytes in the absence of a secondary pathology — 223 cells/mcl. As the number of secondary diseases increases from 1 to 4, we observe consistent reduction in the number of CD4+ lymphosytes; in a combined secondary pathology Ме CD4+ cells did not exceed 100 cells; with 4 and more secondary diseases this figure did not exceed 20 cells in mcl. Correlation analysis of CD4+ cells and the number of combined secondary diseases revealed the presence of moderate connection tightness on the Chaddock scale (r_xy=0,356, p<0,001). The depth of immunodeficiency also affects the outcome of the disease: (M±SD) CD4+ cells in the group of the dead were 101±153 (95% DI: 91–112), in the group of survivors — 198±226 (95% DI:172–224; p<0,001).

Conclusion. Combined secondary disease among patients of ICU infectious hospital were diagnosed in 75.9% patients. There were differences by VL level which increased with the growth of combined lesion number; more significant correlation was found between the amount of CD4+ cells and the number of secondary diseases. The obtained results are confirmed by reduced likelihood of a favorable outcome of the disease with increasing number of combined secondary diseases.

Objective. To identify risk factors of adverse outcome in patients with HIV infection and cytopenia.

Materials and methods. The analyzed group included 30 patients with HIV and two-line cytopenia and pancytopenia. The patients were on inpatient treatment in the Budget Healthcare Institution «CTBD №4», BHCI «Regional Clinical Hospital», Omsk. Results and discussion. Hematopoiesis was found in 14 patients (46,66%), while dyseritropoiesis was noted in 4 patients (13,33%), dysgranulocytopoiesis in 3 patients (10%), cellular rejuvenation of granulocyte series in 2 patients (6,67%), mononuclear cells (involutive forms of megakaryocytes) in 5 patients (13,33%). As HIV progresses the patients experience increasing number and severity of hematological abnormalities in hemograms and myelograms. Early correction of hematopoietic disorders allows to improve the quality of these patients’ life. Myelodysplasia emergence in myelogram in patients with or without ARV therapy statistically differed only in a megakaryocytic germ. The death risk scale of patients with HIV and cytopenia is developed, on the basis of clinical data, obtained results of bone marrow research, based on regression equations.

Introduction. Identification of pharmacogenetic effects on antiretroviral therapy (ART) has become an important milestone to reach in the advancement of personalised treatment for HIV-positive patients. The therapy schemes are accompanied by multiple side effects. Therapy effectiveness and adverse reactions can be dictated by individual genetic predisposition factors, which should be taken into account for an optimal prescription. Some genetic markers (HLA-B*57:01 and UGT1A1*28), were already proven to improve discontinuation rates, and efforts are allocated to expand the range of clinically-relevant genetic tests.

Objective. In this review, an updated summary of genetic polymorphisms and their effects defining patients’ tolerability to ART is presented. The aim of this research is to assess single nucleotide polymorphisms (SNPs) present in the genes that encode proteins involved in ART metabolism and transport. This review will be used to develop a PCR-based testing methodology for the detection and confirmation of risk alleles in the Caucasian population.

Materials and methods. Data from 46 original research papers and reviews was analysed. Allele frequencies of the most relevant polymorphisms were checked against the data for European population.

Results. As an outcome of this review, a few most promising SNPs were selected for future research. Firstly, ABCC4 rs1751034 and rs3742106 and ABCC10 rs9349256 and rs2125739 were associated with an increased risk of renal impairment, higher plasma concentration, and toxicity when treated with tenofovir. Parallel analysis of ABCC4 and ABCC10 SNP effects on renal impairment together with CYP24A1 rs2248359 that was recently reported as a potential renal toxicity marker might be more informative. Secondly, CYP2B6 rs3745274 that was associated with an increased efavirenz plasma concentration, and increased risk of liver and CNS toxicity should be evaluated. SNPs in CYP2B6, CYP2A6 (rs28399433), and CYP3A4 (rs4646437) should be evaluated in parallel since possession of all three variants might put patients at a much higher risk.

Conclusion. Identified alleles could become new markers used in drug prescription protocols if significant effect in Caucasian population will be found. The most relevant SNPs should be tested in in supporting future studies to evaluate the significance for patients with HIV in Russia.

Introduction. One of the main factors affecting TB burden is HIV progression and, in turn, PLWH predominantly die of TB.

The study purpose was to identify high risk regions of HIV, HIV/TB coinfection in NWFD of Russia between years of 2007 to 2018.

Materials and methods. K-means method was applied to identify HIV, HIV/TB incidence, prevalence and mortality rates, as well as share of heterosexual HIV transmission route clusters in 10 regions of NWFD. The need data were extracted from relevant forms of federal statistical observation between 2007 to 2018. NAO was excluded from cluster analysis due to absence of HIV/TB coinfection cases in study period. For holistic understanding of HIV/TB coinfection trends, TB incidence, prevalence and mortality rates were estimated too without including them in cluster analysis.

Results. Along with significant reduce in TB cases there was increase in HIV case data in most regions, especially in Arkhangelsk oblast where HIV incidence raised by 617.8% in period analyzed. Meanwhile Kaliningrad oblast became the only region where HIV incidence (–21.5%) and mortality (–65.6%), also HIV/TB incidence (–55.0%) is failed in 2007–2018. Heterosexual HIV transmission risk was high in almost all regions, especially in NAO (100.0%), Pskov (89.2%), Novgorod (78.8%) oblasts. K-means method detected the highest HIV spread in Arkhangelsk oblast (first cluster), lowest — in Kaliningrad, Leningrad, Murmansk oblasts and St. Petersburg (third cluster). Other regions with intermediate HIV case data formed second cluster. HIV/TB coinfection most rapidly spreads in Arkhangelsk, Pskov and Novgorod oblasts (first cluster), most slowly — in Kaliningrad, Leningrad oblasts and in St. Petersburg (third cluster). In other regions, spread of HIV/TB coinfection has average rate, forming second intermediate cluster.

Conclusion. Along with significant improvement in TB epidemic, spread of HIV and HIV/TB coinfection in regions of NWFD considered as uneven. In regions with high concentration of HIV cases, HIV and HIV/TB coinfection rates are slowed down. Conversely, highest rates of HIV cases, as well as of HIV/TB coinfection case data, are observed in regions with low HIV accumulation, indicating the need to strengthen TB measures in PLWH in regions with a low spread of HIV. 

Introduction. 44 cases of HIV-infection among the homeless were registered in Saint Petersburg in 2021. At the same time, it is known that the case reporting and medical treatment in Russia are limited by the lack of required document minimum among a large number of them — passport and compulsory medical insurance policy. The cohort of the homeless is heterogeneous and in many countries the predominant risk factors of HIV infection and prevalence are different. So far, the studies of HIV spread among the homeless in Russia are rare.

Objective. Assess the prevalence of HIV infection among the homeless in Saint Petersburg.

Materials and methods. Cross-sectional study was carried out among the homeless in «places of attraction»: heating points, overnight shelters, care services from May, 24^th to October, 1^st 2021 and involved 199 participants. There was questionnaire and rapid HIV antibody testing in capillary blood by the set «Wondfo HIV 1,2». The study was completed anonymously.

Results. When examining HIV infection was detected in 9 out of 199 participants — 4.5% (CI 95% [1.61%, 7.39%]), thus, HIV prevalence among the homeless is on average higher than in Saint Petersburg (0.81%) and the country (0.78%). The factors, associated with HIV infection, are the use of injection drugs: odds ratio of prevalence in the adjusted model adjusted prevalence ratio (APR)=4.3 (p<0.05, CI 95% [1.1, 17.5]) and incarceration: APR=9.4 (CI 95% [1.1, 82.2]).

Conclusion. The results obtained and the factors, defined in the study of risk factors for infection, allow to determine the main directions of HIV prevention among the homeless and to highlight the need for attributing the cohort of the homeless to the «key» population group along with others.

Objective. To detect patient’s complaints on admission to the hospital, statistically important with adverse outcome in tuberculosis with HIV infection, most sensitivity and specificity.

Materials and methods. 363 patients were examined with tuberculosis and HIV infection. The first group included 59 (16,3%) patients with adverse disease outcome, the second group contained 304 patients (83,7%) with favorable outcome. Methods: clinical, laboratory, microbiological, statistical: analysis of pairwise contingency tables by Pearson’s criterion, Mann-Whitney test on quantitative characteristics, logistic regression.

Results and discussion. The highest odds ratio of sensitivity and specificity among HIV and tuberculosis patient’s complaints, highly probable on risk of adverse outcome (р<0,0001), has fever — 26,8, 93,2% and 66,1%, loose stools — 25,4, 40,7% and 97,4%, weight loss — 18,8, 72,9% and 87,5%, loss of appetite — 17,0, 69,5% and 88,2%, shortness of breath — 15,6, 79,7% and 79,9%, weakness — 8,7, 91,5% and 44,7%, headache — 7,4, 49,2% and 88,5% accordingly. Thus, in the absence of other complaints the risk of adverse outcome in a patient with HIV and tuberculosis, compared to a patient with no such complaints increases for fever 26,8 times, for loose stools — 25,4 times, for weight loss — 18,8 times, for loss of appetite — 17,0 times, for shortness of breath —15,6 times, for weakness — 8,7 times, for headache — 7,4 times.

Objective. Description of clinical forms of chronic HCV infection in the observed patients, clarifications of options and causes of virological failures of primary interferon-free therapy (DAAT/1) and the results of repeated interferon-free treatment (DAAT/2).

Materials and methods. 8 patients with chronic RNA HCV viremia (subtypes 1b+/–1a and 3а/3ab) were prospectively observed who suffered a virological failure of primary interferon-free therapy with original inhibitors in the form of relapse of RNA HCV viremia and aviremic low-level replication RNA HCV in PBMCs (peripheral mononuclears), but then achieved HCV eradication with a repeated course of interferon-free therapy.

Results. Two variants of virological failures of primary interferon-free therapy were noted — relapse of RNA HCV viremia and aviremic low-level replication of RNA HCV in PBMCs. A number of unfavorable prognosis signs (individual clinical and laboratory syndromes and laboratory parameters) were revealed, which were observed in most patients who did not achieve HCV eradication using primary interferon-free therapy with antiviral drugs: HCV-associated syndromes of low-grade systemic inflammation (LGSI), benign lymphoproliferation and autoantibody production, a high level viral load of HCV RNA viral load in blood plasma, HBV-coinfection without HBsAg and cirrhosis of the liver in the outcome of chronic hepatitis C. The target result of repeated interferon-free therapy, confirmed by the sustainable virological response after 12 weeks after the end of the treatment (SVR12), was achieved in all «losers» of primary interferon-free therapy.

Conclusion. The unfavorable prognostic signs identified in the majority of «losers» of primary interferon-free therapy in the form of individual clinical and laboratory syndromes and laboratory parameters may be associated with potential virological inefficiency of therapy. Based on logistic regression analysis, the value of each of the identified features for predicting different outcomes of primary interferon-free therapy in a large group of patients with HCV is shown. Pangenotypic combinations of GLE/PIB+SOF+/–RBV and VEL/SOF+RBV inhibitors have shown their high antiviral efficacy in the treatment of relapse of RNA HCV viremia and aviremic low-level replication of RNA HCV in peripheral mononuclears for all the patients for whom primary interferon-free therapy was unsuccessful.