EDITORIAL
In this number, we begin publication of case series devoted to epidemiology, clinical picture, diagnosis, treatment, prevention, medical and social consequences of COVID-19. Taking into account the situation anxiety, infection scope and spread rate, involvement of the whole nation into the problem irrespective of gender, age, social affiliations along with comprehensive observing social and medical prevention measures, preemptive training and continuing education of medical specialists are essential considering that novel coronavirus is new not only viewed from its molecular biological features perspective but also from the perspective of possible difficulties of diagnosis and treatment, clinical features, high risk of development of critical con- ditions and complications, high mortality rate that has been shown by an example of China, USA, and European Countries.
In the first report, we tried to highlight the experience gained in the study of novel coronavirus nature, epidemiology, pathogenesis and clinical manifestations, give information from literature sources based on the experience of our colleagues in coping with serious disease and its consequences.
ANALYTICAL REVIEW
The review article is devoted to the state-of-the-art of eradication and functional cure of HIV infection. The issues related to the history of the discovery, characteristics and origin of the main HIV reservoirs, possible approaches to their elimination, exam- ples of the clinical cure of HIV infection and the principal directions of developing tools for targeted destruction of latently infect- ed HIV cell reservoirs are discussed shortly. The circle of methodological approaches for measuring the reservoirs volume is outlined; their advantages and disadvantages are characterized. The procedure for HIV eradication agents’ clinical trials, including the period of analytical interruption of antiretroviral therapy, is described.
LECTURE
General characteristic of hepatitis C virus (HCV) and features of the course of co-infection with human immunodeficiency virus (HIV) was presented. Epidemiologic aspects of these diseases were considered in key populations. Special focus was on pathogenetic components of pathogenic mechanisms in HIV-infected patients with chronic hepatitis C
(CHC).
ORIGINAL STUDIES
IThe aim of this study was to characterize HIV-1 genetic strains currently circulating in Altay Kray (Western Siberia) and to analyze the HIV resistance on this territory.
Materials and methods. Blood samples were collected, with informed consent, in 2017 from 82 HIV infected persons living in Altai Kray. Sequences of pol gene fragments coding protease and part of reverse transcriptase were obtained by in house system and Sanger sequencing. Genotyping, phylogenetic and recombinant analyses were carried out by HIVdbProgram: Sequence Analysis, COMET HIV-1, REGA HIV-1 Subtyping Tool (V 3.0), MEGA 5.05, RIP and jpHMM.
Results and discussion. The results of genotype analysis revealed that the circulating recombinant form CRF63_02A1 dominated in Altay Kray (61%), subtype А was identified in 33%, the remaining subtypes, such as B, G, URF, accounted for 6%. According to phylogenetic analysis results, CRF63_02A1 sequences formed the common branch with nucleotide sequences of strains found in other regions of Siberia and Far East. All of HIV-1 variants belonging to subtype A clustered together with nucleotide sequences of A6 dominating in Russia. RIP analysis allowed to identify three unique recombinant forms (URFs), formed by CRF63_02A1 and A6. Drug resistance mutations were identified in 8 of 21 ART patients (8/21, 38%). The prevalence of drug resistance mutations in naïve patients equaled to 5,1%.
Conclusion. Currently, the process of changing the dominant strain to CRF63_02A1 is ongoing in the Altai Kray, where 13 years ago the main variant was HIV sub-subtype A6 (IDU-A).
The Aim: to evaluate abundance and molecular-genetic characteristics of hepatitis С virus (HCV) among HIV-positive patients residing in the constituent entities of the Far Eastern Federal district.
Materials and methods. Detection of HCV serological markers (HCVsum) was performed via enzyme-linked immunosorbent assay among HIV-positive individuals (n=350) and apparently healthy people (first control group; n=368). In order to conduct comparative evaluation of age-sex composition and HBV-infection markers abundance a second control group of patients with diagnosis of chronic viral hepatitis (n=88) was selected. RNA-positive samples were subjected to molecular-genetic analysis: NS5B HCV genome part (241 bp and 350 bp) was examined.
Results and discussion. The odds ratio of being infected with HCV was over 47 times higher in HIV-population in comparison to apparently health people. HIV-HCV positive patient occurred to be younger rather than patient with diagnosis of chronic viral hepatitis C. It was revealed that in the HIV-HCV co-infected group male patients were prevalent compared to controls. The most prevalent HCV subgenotype was 3a. High prevalence of 3a HCV subgenotype among HIV-infected individuals was probably related to high abundance of intravenous drug use in the studied group. Analysis of the phylogenetic tree showed considerable clusterization of isolated part of gene sequences. This fact can be due to plural infection sources that presumably have no epidemiological connection.
Aim: to compare the incidence of recent cases of HIV infection in the population, recorded by the presence of p24 antigen and in thekit distinguish recent from longstanding infection.
Materials and methods. Evaluation of recent HIV infection was carried out through studies of two cohorts of patients: 1) persons with negative / undetermined result of an immune blot and p24 antigen; 2) individuals with positive immune blot who were additionally studied using a test system to determine the duration of infection. Randomly in 2011, 2013, 2014 and 2015, 22%, 17%, 44% and 6% of all newly identified patients with a positive immune blot, respectively, were examined. Statistical processing, correlation coefficient and confidence intervals were calculated using Student’s t-test.
Results. There is a close correlation between the detection rate of the p24 antigen of HIV and the frequency of occurrence of recent cases of infection registered among newly identified individuals with positive immune blot (the period of probable infection is less than 9 months). Correlation coefficient =0,91, p<0,05.
Conclusion. The established dependence allows one to estimate the recent cases of infection in the population by a calculated method using only the frequency of occurrence of the p24 antigen included in the standard diagnostic algorithm of HIV infection. A formula is proposed in accordance with which it is necessary to add 0,6±0,2 to the frequency of occurrence of the p24 antigen expressed per 1000 individuals covered by screening. With a probability of 95%, the true value of the frequency of occurrence of recent cases of infections in a population will be in the calculated confidence interval.
The Aim: to characterize the immune response to the influenza vaccine in patients with HIV infection with different degrees of immunosuppression.
Materials and methods. 171 HIV-infected adult patients with the different degrees of immunodeficiency and 50 HIV-uninfected persons (control group) were vaccinated against influenza. A single dose of trivalent polymer-subunit vaccine containing adjuvant was administered intramuscularly. The blood titer of antibodies to influenza virus antigens A/H1N1/California/, A/H3N2/Hong Kong/, B/Brisbane/ in the hemagglutination inhibition reaction was determined before vaccination and 21 and 180 days after. The average geometric titers of antibodies were compared between groups of HIV-infected patients with the different degrees of immunosuppression and the control group.
Results. Тhe mean geometric antibody titers increase among HIV-infected with different degrees of immunodeficiency was below 2,0 and the seroconversion rate was below 8,0% for all influenza virus antigens on 21 and 180 days after vaccination. At the same time, during follow-up period in patients with level less than 200 cells /μl of CD4+lymphocytes in blood, the seroconversion index was equal to 0%. The rate of seroprotection to all antigens before vaccination in HIVinfected patients with the different degrees of immunosuppression was above 90%. Naturally, during follow-up period, more than 95,0% of vaccinated patients determined the protective level of antibodies to antigen A /H1N1 and 100,0% of patients to antigen A/H3N2 and B, without reducing this index to the day-180 of observation. Persons from control group showed a sufficient level of seroconversion and seroprotection, corresponding to the criteria of immunogenicity for all antigens of the influenza virus. Conclusion: a single immunization of influenza vaccine does not cause a sufficient degree of serological response in patients with HIV infection, regardless of the severity of immunodeficiency. Seroprotection in case of its developing persists up to 180 day after vaccination.
Aim. Identification of the effectiveness of treatment of newly diagnosed tuberculosis depending on HIV status in the tuberculosis institution of the Federal Penitentiary Service.
Materials and methods: 468 patients with tuberculosis, with HIV infection — 262, without HIV infection — 206 prisoners. Age: from 18 to 62 years.
Results. With treatment in 50% of newly diagnosed patients with tubercu- losis, regardless of HIV status in the tuberculosis institution of the Federal Service for the Execution of Punishments, the termination of the bacteria by microscopy and sowing occurs simultaneously for 3 months. The closure of the cavity (s) of disintegration is achieved one month earlier in patients with HIV infection and is 4 months (statistically insignificant). Thus, in newly diagnosed tuberculosis patients in a tuberculosis institution of the Federal Penitentiary Service, the effectiveness of treatment does not depend on HIV status.
Aim. To evaluate the informativeness indicators of the new diagnostic method «ФП Тест» version 1.0 to determine the moderate/severe degree of hepatitis activity in patients with chronic HCV infection.
Materials and methods. The study included 304 patients with chronic HCV infection. 184 patients were randomly selected into the training sample, 120 patients into the test sample. As a standard method for diagnosing hepatitis activity, a puncture biopsy of the liver was performed in all patients with the calculation of the histological activity index according to the Knodell scale. Minimal/mild degree of hepatitis activity (HAI 0–8 score) was detected in 46,38% of patients, moderate/severe hepatitis activity (HAI 9–18 score) in 53,62% of patients.
Results. The accuracy of the method «ФП Тест» version 1.0 for the diagnosis of moderate/severe hepatitis activity was 79,17%, sensitivity — 78,46%, specificity — 80,00%. The values of the area under the ROC — curve for classifying patients depending on the presence or absence of moderate/severe hepatitis activity were: «ФП Тест» version 1.0 (AUC=0,84, cut-off value=0,52), determination of ALT level (AUC=0,74, cut-off value=61,40 U/L), determination of AST level (AUC=0,76, cut-off value=39,00 U/L).
Conclusion. The new diagnostic method «ФП Тест» is a simple, affordable and informative test to determine the moderate/severe degree of hepatitis activity in patients with chronic HCV infection.
Despite long period of propagation of HIV infection among injecting drug users (IDU) in Russian Federation there is still capacity for appearance of new cases. Based on results of integrated bio-behavioral study conducted in six cities of Russian Federation burden of HIV infection was estimated. Several approaches to calculate disability-adjusted life years (DALY) were used. Estimates of DALY depend mostly on mortality associated with HIV infection. It was shown, that estimates also change depending on changing age-dependent productivity and discount rate. Average loss was estimated at 15,1 DALY per one case of infection. Extrapolating these results on Russian Federation as a whole show that due to continuation of HIV spread among IDU every year 595 thousand DALYs are lost. Summary measures of public health should be used to prioritize investment in prevention.
The epidemic of HIV infection in the last decade has acquired new qualities — first of all, it is an epidemic of severe and comorbid forms of the disease with various pathways of infection, where most of the identified patients need antiretroviral therapy, and most patients die from secondary and concomitant diseases. Therefore, early diagnosis and effective treatment of both the underlying and concomitant diseases are relevant.
Materials and methods. Two clinical cases with fungal infections during a long course of HIV infection in the absence and against the ineffective antiretroviral therapy are presented.
Results. In the cases considered, one of the main reasons for the development of severe damage was late-detected HIV infection at the clinically expressed stages of the disease, which was due to social, psychological and medical (the complexity, and in some cases the inability to perform laboratory tests) fac- tors.
Conclusion. Fungal lesions during HIV infection are diverse in their etiology, forms of manifestation and severity of the clinical course. The development of optimal algorithms and approaches for medical and psychosocial support of such patients is necessary. The high mortality rate of patients with HIV infection in the first week of hospital stay is often evidence of non-adherence to dispensary observation and treatment, all the more so because amid low adherence to specific therapy and chemoprophylaxis, treatment of opportunistic diseases without antiretroviral therapy is ineffective (although the timely appointment of this therapy is considered a universal method for the prevention of secondary diseases). The treatment-diagnostic tactics in diagnostically unclear cases are discussed.
CLINICAL PRACTICE
Objectives. This work aims to provide retrospective analysis of socio-economic, demographic and clinical features of patients with HIV infection in 5 regions of Russian Federation with high prevalence of HIV infection (Krasnoyarsk, Tomsk, Irkutsk, Ulyanovsk Region, Samara Region).
Materials and methods. A study was a part of the project «Natural and Clinical Course of HIV Infection in the Russian Federation». The protocol of study included a retrospective analysis of the regional Centers for the Prevention and Control of AIDS registers and medical records of patients. Inclusion criteria was a verified diagnosis of HIV infection. Diagnosis should be made by 01/01/2015 at the latest.
Results. Demographic and socio-epidemiological parameters, clinical manifestations, immunological aspects and the status of antiretroviral therapy in the studied cohort were evaluated. The results of the analytical study allowed us to present a modern profile of the HIV-infected population.
Discussion. The analysis showed the prevalence of socially adapted people of working age (30–39 years), the predominance of the parenteral route of HIV infection associated with intravenous drug use in men and the activation of the sexual route of HIV infection in a cohort of women, and other features of HIV epidemiology. Results of analytical work reflect the situation of HIV infection in the Russian Federation, justifying the need for further research in this area and implementing effective prevention strategies into practice.
Aim: to carry out the comparative analysis of Russian kits for HIV-1 viral load (VL) measuring: AmpliSens HIV-monitor-FRT, AmpliSens HIV-monitor-Duo-FL, RealBest RNA HIV quantitative, HIV-GEN quantitative.
Materials and methods: we analyzed the collection of clinical blood plasma samples with VL 590–2,05×106 copies/ml, dilutions of HIV-1 2nd International Standard, as well as panels of subtypes and recombinant forms of HIV-1 group M. The convergence of the results was determined using the Spearman correlation analysis and the Bland-Altman method.
Results. A high level of convergence of VL measuring results in clinical samples (n=76) was determined for all compared kits with the value of approximation reliability R of at least 0,85. The maximum difference between the median values of VL results (0,48 log, ≈3-fold) was obtained for HIVMonitor-FRT and RealBest quantitative, which did not exceed the acceptable discordance rate in two kits comparing. All dilutions of the 2nd international HIV-1 standard were successfully determined by all kits with middle error 0,16–0,34 lg copies/ml. All kits successfully revealed the most of HIV-1 subtypes and recombinants studied with middle deviation 0,02–0,56 log copies/ml. HIV-GEN quantitative demonstrated the highest accuracy, but didn’t reveal ADG-recombinant.