Antiviral Therapy Regimens Research Articles

Modern etiotropic therapy of chronic viral hepatitis B

Chronic viral hepatitis B (CHB) is a significant global health problem. The biological characteristics of the hepatitis B virus, which causes this disease, significantly impede the achievement of complete virus elimination in most patients. In this regard, the rational choice of drugs and antiviral therapy regimens is crucial for increasing life expectancy and improving the quality of life in patients with CHB. The purpose of this literature review is to identify current approaches and trends in etiotropic therapy for CHB.Materials and methods. The review uses data published in domestic and foreign scientific journals, clinical guidelines, regulatory documents, and Internet resources.Results. Currently, the most effective means of etiotropic therapy for CHB are interferons (standard interferon alpha, pegylated interferons alpha-2a and alpha-2b), as well as first-line nucleoside/nucleotide analogs (entecavir, tenofovir) and second-line analogs (lamivudine, telbivudine, adefovir). The choice of a specific drug is determined by the patient's clinical condition, preferences, availability, and cost of treatment. Despite certain limitations of current etiotropic therapies for CHB, their use can significantly increase patients' life expectancy and improve their quality of life.

HIV-Associated Hypertension: Risks, Mechanisms, and Knowledge Gaps.

HIV type 1 (HIV-1) is the causative agent of AIDS. Since the start of the epidemic, HIV/AIDS has been responsible for ≈40 million deaths. Additionally, an estimated 39 million people are currently infected with the virus. HIV-1 primarily infects immune cells, such as CD4+ (cluster of differentiation 4+) T lymphocytes (T cells), and as a consequence, the number of CD4+ T cells progressively declines in people living with HIV. Within a span of ≈10 years, HIV-1 infection leads to the systemic failure of the immune system and progression to AIDS. Fortunately, potent antiviral therapy effectively controls HIV-1 infection and prevents AIDS-related deaths. The efficacy of the current antiviral therapy regimens has transformed the outcome of HIV/AIDS from a death sentence to a chronic disease with a prolonged lifespan of people living with HIV. However, antiviral therapy is not curative, is challenged by virus resistance, can be toxic, and, most importantly, requires lifelong adherence. Furthermore, the improved lifespan has resulted in an increased incidence of non-AIDS-related morbidities in people living with HIV including cardiovascular diseases, renal disease, liver disease, bone disease, cancer, and neurological conditions. In this review, we summarize the current state of knowledge of the cardiovascular comorbidities associated with HIV-1 infection, with a particular focus on hypertension. We also discuss the potential mechanisms known to drive HIV-1-associated hypertension and the knowledge gaps in our understanding of this comorbid condition. Finally, we suggest several directions of future research to better understand the factors, pathways, and mechanisms underlying HIV-1-associated hypertension in the post-antiviral therapy era.

Immune reconstitution and influencing factors in HIV infected men who have sex with men with access to antiviral therapy in Guangxi Zhuang Autonomous Region from 2005 to 2021

Objective: To analyze immune reconstitution and influencing factors in HIV infected men who have sex with men (MSM) with access to antiviral therapy (ART) in Guangxi Zhuang Autonomous Region (Guangxi) during 2005-2021. Methods: The data were collected from Chinese Disease Prevention and Control Information System. The study subjects were HIV infected MSM with access to the initial ART for ≥24 weeks in Guangxi from 2005 to 2021 and HIV RNA lower than the detection limit within 24 months. The proportion of infected MSM who had immune reconstitution after ART was calculated. Cox proportional hazard regression model was used to analyze the influencing factors of immune reconstitution. Software SPSS 24.0 was used for statistical analysis. Results: A total of 3 200 HIV infected MSM were enrolled, in whom 15.56 % (498/3 200) had no immune reconstitution, 14.78% (473/3 200) had moderate immune reconstitution, and the rate of complete immune reconstitution was 69.66% (2 229/3 200). The M (Q1, Q3) of ART time for immune reconstitution was 12 (5, 27) months. Multivariate Cox proportional risk regression model analysis results showed that compared with those with initial ART at age ≥30 years, WHO clinical stage Ⅲ/Ⅳ illness, baseline BMI <18.50 kg/m2 and baseline CD4+T lymphocyte (CD4) counts <200 cells/µl, HIV infected MSM with initial ART at age <30 years, WHO clinical stageⅠ/Ⅱ illness, baseline BMI≥24.00 kg/m2 and baseline CD4 counts ≥200 cells/µl were more likely to have complete immune reconstitution. Conclusions: In the HIV infected MSM in Guangxi, failures to achieve moderate and complete immune reconstitution were observed. Surveillance and ART regimen should be improved for key populations, such as those with older age and low baseline CD4 counts.

RESULTS OF ANTIFIBROTIC THERAPY IN PATIENTS WITH CHRONIC HEPATITIS B+C

Modern antiviral therapy regimens for patients with chronic viral hepatitis aim to achieve either long-term suppression of pathogen replication (e.g., nucleoside analogs in chronic hepatitis B) or complete elimination of the virus (such as direct-acting antiviral drugs in chronic hepatitis C). However, antiviral agents do not have a significant impact on the complete restoration of biochemical processes or the prevention of further progression of morphological changes in the liver. These limitations emphasize the ongoing need for new therapeutic strategies that target the processes of fibrogenesis.&#x0D; The aim of the work is to assess the possibility of the effect of the drug "Bicyclol" on fibrotic changes in patients with chronic hepatitis B+C using a non-invasive scale of the rate of fibrosis.&#x0D; Materials and methods&#x0D; An analysis of the dynamics of 62 patients with chronic hepatitis B and C (HCV+C) was conducted. All patients received long-term antiviral therapy consisting of pegylated interferon for 48 weeks. In the main group (Group I), patients with chronic hepatitis B and C were prescribed the drug "Bicyclol" after completing antiviral treatment with interferon. The control group (Group II) followed the principles of proper nutrition and took traditional hepatoprotectors. Based on the identified correlations, a non-invasive scale was proposed to assess the individual risk of liver fibrosis progression.&#x0D; Research results&#x0D; Against the background of the use of an antiviral treatment regimen, the normalization of cytolysis indicators was observed in most patients with CHB+C, but in some patients it was short-lived. Treatment with the drug "Bicyclol" contributed to a further decrease in cytolysis indicators, in the vast majority of patients with CHB+C, the activity of ALT and AST reached the upper limit of the norm. In patients with CHB+C who received only basic treatment without an antifibrotic component, a tendency to maintain an elevated level of transaminases was observed.&#x0D; Conclusions.&#x0D; Thus, the use of the hepatoprotector "Bicyclol" for 12 months ensures a decrease in cytolysis in the liver, is accompanied by a decrease in the severity of fibrosis, and in some patients - its reverse development. The use of the proposed prognostic scale makes it possible to assess the need for early appointment of antifibrotic therapy.

Curcuma Longa Induces the Transcription Factor FOXP3 to Downregulate Human Chemokine CCR5 Expression and Inhibit HIV-1 Infection.

HIV mutations occur frequently despite the substantial success of combination antiretroviral therapy, which significantly impairs HIV progression. Failure to develop specific vaccines, the occurrence of drug-resistant strains, and the high incidence of adverse effects due to combination antiviral therapy regimens call for novel and safer antivirals. Natural products are an important source of new anti-infective agents. For instance, curcumin inhibits HIV and inflammation in cell culture assays. Curcumin, the principal constituent of the dried rhizomes of Curcuma longa L. (turmeric), is known as a strong anti-oxidant and anti-inflammatory agent with different pharmacological effects. This work aims to assess curcumin's inhibitory effects on HIV in vitro and to explore the underpinning mechanism, focusing on CCR5 and the transcription factor forkhead box protein P3 (FOXP3). First, curcumin and the RT inhibitor zidovudine (AZT) were evaluated for their inhibitory properties. HIV-1 pseudovirus infectivity was determined by green fluorescence and luciferase activity measurements in HEK293T cells. AZT was used as a positive control that inhibited HIV-1 pseudoviruses dose-dependently, with IC50 values in the nanomolar range. Then, a molecular docking analysis was carried out to assess the binding affinities of curcumin for CCR5 and HIV-1 RNase H/RT. The anti-HIV activity assay showed that curcumin inhibited HIV-1 infection, and the molecular docking analysis revealed equilibrium dissociation constants of [Formula: see text]9.8[Formula: see text]kcal/mol and [Formula: see text]9.3[Formula: see text]kcal/mol between curcumin and CCR5 and HIV-1 RNase H/RT, respectively. To examine curcumin's anti-HIV effect and its mechanism in vitro, cell cytotoxicity, transcriptome sequencing, and CCR5 and FOXP3 amounts were assessed at different concentrations of curcumin. In addition, human CCR5 promoter deletion constructs and the FOXP3 expression plasmid pRP-FOXP3 (with an EGFP tag) were generated. Whether FOXP3 DNA binding to the CCR5 promoter was blunted by curcumin was examined using transfection assays employing truncated CCR5 gene promoter constructs, a luciferase reporter assay, and a chromatin immunoprecipitation (ChIP) assay. Furthermore, micromolar concentrations of curcumin inactivated the nuclear transcription factor FOXP3, which resulted in decreased expression of CCR5 in Jurkat cells. Moreover, curcumin inhibited PI3K-AKT activation and its downstream target FOXP3. These findings provide mechanistic evidence encouraging further assessment of curcumin as a dietary agent used to reduce the virulence of CCR5-tropic HIV-1. Curcumin-mediated FOXP3 degradation was also reflected in its functions, namely, CCR5 promoter transactivation and HIV-1 virion production. Furthermore, curcumin inhibition of CCR5 and HIV-1 might constitute a potential therapeutic strategy for reducing HIV progression.

Comorbidity and multimorbidity in patients with chronic hepatitis C

The aim of the study was to analyze comorbidity in patients who underwent a course of antiviral therapy for chronic hepatitis C with direct antiviral drugs.Materials and methods: 288 patients diagnosed with chronic hepatitis C with stages of liver fibrosis from F1 to F4 according to the METAVIR scale, various genotypes, who underwent antiviral therapy with direct antiviral drugs in the period from 2018 to 2021, were under observation, with an analysis of comorbid and multimorbid diseases.Results of the study: most often in these patients, regardless of gender and antiviral therapy regimen, lesions of the gastrointestinal tract were registered in the form of various inflammatory diseases, as well as non-alcoholic fatty liver disease. In second place in terms of frequency of occurrence, diseases of the endocrine system were diagnosed, primarily due to the development of metabolic syndrome, as well as damage to the thyroid gland, as an extrahepatic manifestation of chronic HCV infection. Slightly less marked diseases of the cardiovascular system. A relationship was found between the number of comorbid diseases and the body mass index, with an increase in which the stage of liver fibrosis progresses.Conclusions: The frequency of comorbidity and multimorbidity in patients with chronic HCV infection is significantly higher than in uninfected patients. Patients with chronic hepatitis C with advanced stages of liver fibrosis (F3 and F4 according to the MEVIR scale) with overweight and obesity of varying severity are characterized by the highest incidence of comorbidities. A variety of extrahepatic manifestations of chronic hepatitis C determine the polymorbid profile of the patient.

Distribution of Epstein-Barr Virus and Human Herpesvirus 8 Co-Infections among Human Immunodeficiency Virus -1 Positive Patients

Background and Aims: Among Human Immunodeficiency Virus (HIV)-infected individuals, Epstein-Barr virus (EBV) and Human Herpesvirus (HHV)-8 could cause significant illness as opportunistic infections. The purpose of the present study was to evaluate the prevalence of EBV andHHV-8 in saliva specimens obtained from HIV-1 infected Iranian individuals under the Highly Active Antiviral Therapy (HAART) regimen compared with naïve patients.&#x0D; Materials and Methods: A cross-sectional study was conducted on 103 HIV-1 positive patients who attended the hospitals affiliated with the Iran University of Medical Sciences, in Tehran, Iran, from 2018 to 2019. Enzyme-linked immunosorbent assay (ELISA) test was performed to evaluate HHV-8 and EBV antibodies. A conventional polymerase chain reaction (PCR) was carried out on saliva samples to detect EBV infection and a nested-PCR assay for HHV-8 infection. SPSS (version 20) was used for statistical analysis.&#x0D; Results: Patients' mean age ± SD was 43.9 ± 16 (range 18-82 years), and from among 103 participants, 59 (57.3%) were male. The results of PCR showed that HHV-8 infection was found in 19 (18.4%), and EBV infection was found in 61 (59.2%) participants. Also, HHV-8 antibody was detected in 73 (70.9%), and EBV antibody in 97 (94.2%) patients. A significant association was observed between patients under treatment with HAART and HHV-8 DNA or EBV DNA infection in saliva.&#x0D; Conclusions: HIV-infected patients demonstrated a remarkable rate of EBV and HHV-8 in saliva, which could have a great role in the shedding of viruses. Also, they may contribute to the establishment of further opportunistic infections and devastating complications.

КЛИНИЧЕСКОЕ ТЕЧЕНИЕ И ВЫБОР ПРОТИВОВИРУСНОЙ ТЕРАПИИ ХРОНИЧЕСКОГО ГЕПАТИТА В С УЧЕТОМ МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИХ СВОЙСТВ ВОЗБУДИТЕЛЯ

Background. The clinical course of chronic hepatitis B (CHB) as well as the efficacy of its antiviral therapy depend on the genetic properties of the virus. Objective. To study the clinical and laboratory parameters of patients with CHB and their dependence on the molecular genetic properties of HBV in order to optimize the choice of antiviral therapy regimen. Material and methods. The study included 231 patients with CHB. Routine hematological and biochemical tests, serum HBV DNA level, liver fibrosis stage were measured. Phylogenetic analysis of HBV was carried out in 90 patients. Results. HBV DNA level above 2000 IU/ml was found in 68.8% of patients. Phylogenetic analysis revealed the circulation in Gomel region of HBV genotypes D (76.7%) and A (22.2%), genotype C being detected as well. Patients with genotype D had higher levels of aminotransferases and gamma-glutamiltransferase as well as higher liver fibrosis indices (p&lt;0.05) as compared to those with genotype A; no differences in viral load were found. Antiviral treatment is indicated in 66.7% of patients with genotype D, and only in 35% of those with genotype A (p=0.01). Nucleos(t)ide analogues are optimal as initial antiviral therapy for 86.8% of patients with indications for treatment. Conclusions. The determination of HBV viral load and genotype is important for predicting liver disease severity and choosing the optimal antiviral therapy regimen.

Влияние рекомбинантного интерферона α-2b на цитокинпродуцирующую активность клеток иммунной системы у детей с COVID-19

The clinical efficacy of recombinant IFN-α2b in therapy for COVID-19 in children is the basis for studying the parameters of the cytokine production activity of immune system cells and will allow to optimize antiviral therapy regimens. Objective. To study the effect of recombinant IFN-α2b on serum IFN-α and IFN-γ concentrations and their synthesis by immune system cells in children with COVID-19. Materials and methods. Peripheral blood samples from 100 patients aged 1 to 17 years (1–7 years – 50 people, 8–17 years – 50 people) with a moderate course of COVID-19 were examined. Patients in the study group received recombinant IFN-α2b as Вклюpart of complex therapy. Patients in the comparison group received antiviral therapy with Arbidol®. Multiplex analysis was used to determine serum IFN-α and IFN-γ concentrations and the level of their synthesis by immune system cells. The enzyme-linked immunosorbent assay (ELISA) was used to determine serum concentrations of antibodies to IFN-α. Results. Combination therapy with recombinant IFN-α2b in children of both age groups led to an increase in serum IFN-α concentrations compared to baseline values prior to treatment, in children in the control group and patients with COVID-19 after treatment with Arbidol. There were no significant changes in serum IFN-α and IFN-γ concentrations and their synthesis in intact and PHA-stimulated cells in children of both age groups during treatment with Arbidol. Serum concentrations of antibodies to IFN-α during treatment with recombinant IFN-α2b did not depend on the age of children and remained within the reference range. Conclusion. A significant increase in serum IFN-α concentrations and restoration of its synthesis level induced by PHA to reference values indicate that the use of recombinant interferon medications with their antiviral and immunomodulatory effects should become an integral part of COVID-19 therapy. Key words: children, COVID-19, recombinant interferon IFN-α2b, serum IFN-α concentrations, IFN-α synthesis levels

The Effectiveness and Safety of Convalescent Plasma as a Therapy for COVID-19 Patients: A Literature Review

COVID-19 is a new disease caused by SARS-CoV-2 with an increasing number of cases. until now, no specificvaccine or antiviral therapy regimen has yet been found. A therapy that has been known for approximately acentury ago called convalescent plasma therapy has been discussed again as an effective and safe therapy forCOVID-19 patients. Conduct a literature review of scientific studies related to the effectiveness and safetyof convalescent plasma as a therapy for COVID-19 patients. Convalescent plasma has proven to be effectivebecause it can improve the clinical condition felt by patient, prevent the entry of viruses into cells and inhibitthe virus replication. This therapy is also proven to have no harmful effects, so it is safe to be performed bypaying attention to certain things such as conditions that must be fulfilled by the donors.

Anemia and thrombocytopenia in people living with HIV/AIDS: a narrative literature review.

Hematologic changes are frequent complications in people living with HIV/AIDS (PLWHA). Anemia and thrombocytopenia are the most frequent multifactorial hematologic abnormalities and are associated with a low quality of life and high death rates. This study aims to describe the prevalence of anemia and thrombocytopenia in PLWHA and to identify the main clinical characteristics that aggravate these conditions in studies published in the last 10 y. A comprehensive search was performed on the PUBMED database, using the terms ‘HIV infection and anemia’ and ‘HIV infection and thrombocytopenia’. Additional searches were made in the reference lists of articles covering the theme. The selected studies reported an overall prevalence of anemia from 7.2% to 84% and of thrombocytopenia from 4.5% to 26.2%. The prevalence of thrombocytopenia and anemia were aggravated by a CD4+ T lymphocyte count of <200 cells/μL, increased viral load and coinfections or opportunistic infections. Antiviral therapy (ART) shows a beneficial effect, reducing the frequencies of thrombocytopenia and anemia, except in a zidovudine-based ART regimen, which worsens the anemic condition. Because anemia and thrombocytopenia are treatable comorbidities associated with increased mortality among PLWHA, physicians should monitor these risk factors in order to establish better interventions and reduce morbidity and mortality in PLWHA.

The level of expression of miR-196a in patients with chronic viral hepatitis C with the first genotype of HCV according to previous experience of antiviral therapy.

The authors present the study of the level of expression of miR-196a in 74 patients with chronic viral hepatitis C with the 1st genotype of HCV, based on previous experience in patients with antiviral therapy regimens containing interferon. The patients were divided into two groups, depending on the previous experience of antiviral therapy with circuits containing interferon – 21 patients who failed after antiviral therapy regimens containing interferon (group 1) and the comparison group (group 2) – 53 naive patients. To study the level of expression of miR-196a (miR-196a), a two-stage study according to the manufacturer's protocol was used. First, total RNA was isolated from the plasma by the method of phenol-chloroform extraction. Futher reverse transcription was performed using a kit for reverse transcription of miR TaqMan® (Applied Biosystems, USA), specific loop primers to achieve mature miRNA, snRNA U6 (as an endogenous control gene), and 10 ng of total RNA. Real-time quantitative PCR was performed using TaqMan® miRNA analysis. In order to optimize the prediction of response to antiviral therapy and the use of optimal treatment regimens for problem patients with treatment failure regimens containing interferon, analysis using ROC curves was used. The average level of expression of miR-196a in patients with chronic hepatitis C was evaluated. In the 1st group of patients it was 0.011 (IQR: 0.002; 0.310) and in the comparison group – 0.346 (IQR: 0.054; 1.239) at p=0.012 by U criterion. The conducted ROC analysis showed that the studied miR-196a could differentiate patients with chronic viral hepatitis C with HCV genotype 1, depending on previous experience of antiviral therapy, namely, patients with treatment failure regimens containing interferons and naive. AUC=0.688 (95% CI 0.570-0.791; p=0.017), J=0.40, Se=57.14%, Sp=83.02%. It gives additional opportunities for correction of therapeutic tactics. Therefore, the level of expression of miR-196a (&lt;-1,75) may be an additional biomarker in the pathogenesis of HCV-infection, which can then be used in the monitoring and treatment of patients. Low expression of miR-196a may be the basis for prescribing more effective direct-acting antiviral therapy to patients and will allow personalizing therapeutic tactics in patients with chronic viral hepatitis C.

Interim Guidelines on Antiviral Therapy for COVID-19.

Since the first case was reported in Wuhan, Hubei Province, China on December 12, 2019, Coronavirus disease 2019 (COVID-19) has spread widely to other countries since January 2020. As of April 16, 2020, 10635 confirmed cases have been reported, with 230 deaths in Korea. COVID-19 patients may be asymptomatic or show various clinical manifestations, including acute symptoms such as fever, fatigue, sore throat; pneumonia presenting as acute respiratory distress syndrome; and multiple organ failure. As COVID-19 has such varied clinical manifestations and case fatality rates, no standard antiviral therapy regimen has been established other than supportive therapy. In the present guideline, we aim to introduce potentially helpful antiviral and other drug therapies based on in vivo and in vitro research and clinical experiences from many countries.

Nosocomial respiratory viral infections: state of the problems

We scanned the PubMed search database for literature on the incidence of nosocomial respiratory viral infections (NRVI) published over a ten-year period. Necessity to apply the standard case definition and the laboratory panel based on the multiplex polymerase chain reaction in frequency assessment was established. In general, predominance of rhinoviruses in the etiological structure was detected. Rationale was given for introduction of nonspecific epidemic prevention activities against a broad spectrum of other respiratory pathogens including high-priority respiratory syncytial viruses, metapneumoviruses, adenoviruses, influenza and parainfluenza viruses and coronaviruses. Bocaviruses and mimiviruses were designated as rare species. The biological diversity of the pathogens causing NRVI calls for active promotion of molecular genetics techniques in the work of the laboratory services of health facilities to perform quality etiological diagnosis, design relevant antiviral therapy regimens and effective prevention programs whose implementation will lead to significant reduction in the spread risk of these infections and the treatment costs.

Chronic hepatitis C: modern condition of the problem

Chronic hepatitis C (CHC) is one of the common chronic viral infections. Current advances in the treatment of chronic hepatitis C have allowed WHO to develop a Global health sector strategy on viral hepatitis for 2016-2021 with the purpose of its elimination by 2030. Antiviral drugs of new generations have therapeutic efficacy of more than 98% and wide indications for use. At the same time, there are special groups of patients in whom the choice of antiviral therapy regimen is limited and its effectiveness differs from the general population of patients with chronic hepatitis C. This review provides data on the epidemiology, pathogenesis, clinical manifestations of CHC, and current approaches to the treatment of the disease. Particular attention is paid to patients with extrahepatic manifestations of chronic HCV infection.

Mother-to-child transmission of hepatitis B virus after amniocentesis: A retrospective matched cohort study.

The objective of this study is to determine whether amniocentesis increases the risk of mother-to-child transmission (MTCT) of hepatitis B virus (HBV) and evaluate risk factors for MTCT. One hundred forty-three hepatitis B surface antigen (HBsAg)-positive women with amniocentesis were enrolled into the amniocentesis group. Six hundred five nonamniocentesis cases were matched with amniocentesis cases based on maternal viral loads, antiviral therapy regimens, and delivery dates. MTCT of HBV was defined as HBsAg and/or DNA positivity in infants from birth to age 7 to 12 months. Mother-to-child transmission rate was significantly higher in HBsAg-positive women with amniocentesis than in those without amniocentesis (2.80% vs 0.50%; relative risk [RR], 5.64; 95% CI, 1.28-24.93). In the amniocentesis group, maternal HBV DNA more than or equal to 7.0 log10 IU/mL and hepatitis B e-antigen (HBeAg) positivity were associated with higher MTCT rates than maternal HBV DNA less than 7.0 log10 IU/mL (10.81% vs 0%, p = .004) and HBeAg negativity (8.16% vs 0%, p = .013), and antiviral therapy reduced MTCT rate from 14.3% to 0% (p = .554) when maternal HBV DNA was more than or equal to 7.0 log10 IU/mL. Amniocentesis increases the risk of MTCT in women with hepatitis B, and maternal HBV DNA more than or equal to 7.0 log10 IU/mL and HBeAg positivity are risk factors for MTCT. Antiviral therapy may be effective to prevent MTCT after amniocentesis in highly viremic mothers.

Restoration of HCV-Specific Immune Responses with Antiviral Therapy: A Case for DAA Treatment in Acute HCV Infection.

Worldwide, 71 million individuals are chronically infected with Hepatitis C Virus (HCV). Chronic HCV infection can lead to potentially fatal outcomes including liver cirrhosis and hepatocellular carcinoma. HCV-specific immune responses play a major role in viral control and may explain why approximately 20% of infections are spontaneously cleared before the establishment of chronicity. Chronic infection, associated with prolonged antigen exposure, leads to immune exhaustion of HCV-specific T cells. These exhausted T cells are unable to control the viral infection. Before the introduction of direct acting antivirals (DAAs), interferon (IFN)-based therapies demonstrated successful clearance of viral infection in approximately 50% of treated patients. New effective and well-tolerated DAAs lead to a sustained virological response (SVR) in more than 95% of patients regardless of viral genotype. Researchers have investigated whether treatment, and the subsequent elimination of HCV antigen, can reverse this HCV-induced exhausted phenotype. Here we review literature exploring the restoration of HCV-specific immune responses following antiviral therapy, both IFN and DAA-based regimens. IFN treatment during acute HCV infection results in greater immune restoration than IFN treatment of chronically infected patients. Immune restoration data following DAA treatment in chronically HCV infected patients shows varied results but suggests that DAA treatment may lead to partial restoration that could be improved with earlier administration. Future research should investigate immune restoration following DAA therapies administered during acute HCV infection.

Basic principles of management of patients with genital herpes

Background. Genital herpes is a chronic recurrent sexually transmitted viral disease. Recurrent genital herpes is a serious medical and psychosocial issue which significantly worsens patients’ quality of life. Such a course of the disease is a stressful and psycho-traumatic factor limiting patients’ social life. In addition, in about 10% of cases, relapses of genital herpes cause depression, acute psychosis and suicidal tendencies. Herpesvirus infection occupies a leading position among perinatal TORCH infections. Herpes infection exerts an unfavorable and often fatal effects on pregnancy and childbirth and it is of a relevant issue up today since its role in causing fetal and newborn disorders does not tend to decrease. Current an increase in genital herpes relapse rate dictates need for further research. Study of various etiotropic antiviral therapy regimens effectiveness is necessary for the further elaboration of optimal treatment regimens and preparation for pregnancy. Aim. To search for adequate etiotropic antiviral therapy regimens aimed at reducing genital herpes relapse rate. Materials and methods. To write this review domestic and foreign publications were searched in Russian and international search systems (PubMed, eLIBRARY, etc.) for the last 2-10 years. The review includes articles from peer-reviewed literature. Results. The review describes features of genital herpes clinical course, its diagnosis, differentiated diagnosis and complications. Various treatment regimens are presented. The effectiveness of etiotropic therapy with various drugs was estimated. Conclusions. Episodic use of valaciclovir for recurrent genital herpes allows to reduce significantly a current relapse severity and duration as well as to provide psychological support to patients.

Comparative clinical and economic evaluation of two alternative antiviral therapy regimens for influenza patients

Comparative clinical and economic evaluation of two alternative antiviral therapy regimens for influenza patients

Treatment of Hepatitis C Infection with Direct-Acting Antiviral Agents in Liver-Transplant Patients: A Systematic Review and Meta-Analysis

Context: Recurrence of hepatitis C virus (HCV) infection after liver transplantation (LT) can be prevented, using antiviral therapy and new treatment regimens. Combination of protease, NS5A, and NS5B inhibitors, with or without pegylated-interferon and ribavirin (PEG-IFN/RBV), results in significantly high rates of sustained virologic response (SVR) among post-LT patients with HCV infection. In this study, we aimed to assess the efficacy of direct-acting antiviral (DAA) regimens in post-LT patients with HCV infection. Evidence Acquisition: We conducted a systematic search in electronic databases to detect eligible studies on DAA treatments after LT. We evaluated English-language studies, including clinical trials and cohort studies, which used antiviral DAA regimens (with or without PEG-IFN/RBV) and reported SVR rates at 12 weeks after the end of treatment (SVR12). After data extraction, the pooled SVRs were calculated, using STATA version 11. Results: A total of 35 studies with various HCV genotypes were included in our analysis. Due to the small sample size and lack of suitable data on HCV genotypes 2 - 6, the meta-analysis was only conducted among patients with HCV genotype 1; the results of other studies were also obtained. SVR12 rates ranged from 91% to 97% in patients with 12- or 24-week sofosbuvir (SOF)/simeprevir (SMV) ± RBV, SOF/ledipasvir (LDV) ± RBV, and SOF/daclatasvir (DCV) ± RBV regimens. The minimum SVR12 rate was found in patients receiving SMV plus PEG-IFN/RBV (59%; 95% Confidence Interval, 49 - 68). Conclusions: Administration of new HCV DAA regimens can prevent post-LT HCV infection. The combination of SOF/DCV and SOF/LDV, with or without RBV, for 12 or 24 weeks can produce high rates of SVR12 in post-LT HCV patients in different settings.