Background: Use of ART as the only effective way to control HIV infection results in HIV drug resistance. NGS became the common method for identifying drug-resistant variants and reducing analysis costs. The aim of the study was to develop the NGS based protocol for identifying resistance mutations and cell tropism of HIV-1 in adult patients with and without treatment experience in Russia in 2024–2025. Methods: Plasma samples from adult HIV-infected patients from Russia were analyzed. Consensus nucleotide sequences of pol and env genes were obtained using Illumina NextSeq NGS. HIV-1 drug resistance analysis was conducted using Stanford University HIVdb database. CXCR4 cell tropism was predicted using empirical rule classifier. Results: The protocol for NGS of HIV-1 pol and env genes was developed. The most common HIV-1 surveillance mutations were in the reverse transcriptase. In treatment-experienced patients, high levels of resistance were observed to NNRTIs and NRTIs, and in treatment-naive— to NNRTIs. Low levels of resistance were observed to protease and integrase inhibitors. CXCR4 cell tropism was extremely rare. Conclusion: NGS allows for the simultaneous processing of large data sets during epidemiological studies. The introduction of NGS based protocols allows performing ART efficiency and tropism monitoring at scale.

The use of antiretroviral therapy (ART) as the only effective way to control human immunodeficiency virus (HIV) infection results in HIV drug resistance. Next-generation sequencing (NGS) has become a common method for identifying drug-resistant variants and reducing analysis costs. The aim of this study was to develop an NGS-based protocol for identifying resistance mutations and cell tropism of HIV-1 in adult patients with and without treatment experience in Russia in 2024–2025. Plasma samples from adult HIV-infected patients from Russia were analyzed. Consensus nucleotide sequences of pol and env genes were obtained using NGS. HIV-1 drug resistance analysis was conducted using the Stanford University HIVdb database. CXCR4 cell tropism was predicted using an empirical rule classifier. A protocol for NGS of HIV-1 pol and env genes was developed. The most common HIV-1 surveillance mutations were in the reverse transcriptase. High levels of resistance were observed to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs) in treatment-experienced patients and to NNRTIs in treatment-naïve patients. Low levels of resistance were observed to protease and integrase strand transfer inhibitors (INSTIs). CXCR4 cell tropism was extremely rare. NGS allows for the simultaneous processing of large data sets during epidemiological studies. The introduction of NGS-based protocols allows for performing ART efficiency and tropism monitoring at scale.

BackgroundStress and financial concerns due to the COVID-19 pandemic are well documented, with mixed evidence regarding their relationship with substance use. This mixed-methods study describes the prevalence of pandemic-related stress and financial worry, and their association with changes in substance use among people with HIV with a history of injection drug use in Russia.MethodsWe conducted a secondary analysis of survey and qualitative data collected from two trials between May 2020 and July 2021. We used multivariable logistic regression to assess associations between pandemic-related stress and financial worry, and reported changes in illicit opioids (primary), cigarettes (secondary), and alcohol (exploratory) use. The outcome was defined as any change (increase, decrease, or stopping) in substance use. A thematic analysis of semi-structured interviews explored experiences of stress and substance use during the pandemic.Results and conclusionsAmong 132 survey participants, 52% reported high pandemic financial worry and 31% reported high pandemic stress. Overall, 22% reported changes in opioid use (20% decrease, 2% increase), 21% in cigarette smoking (18% decrease, 3% increase), and 15% in alcohol use (9% decrease, 6% increase). High stress was associated with reporting any change in opioid use due to the pandemic (AOR 2.98; 95%CI: 1.20, 7.40; p = 0.02). Financial worry showed a similar but imprecise association (AOR 2.45; 95%CI: 0.96, 6.21; p = 0.06). No associations were observed for cigarette or alcohol use. Qualitative findings indicated that pandemic-related stressors and disruptions in drug access may have been linked to substance use patterns for some participants, although changes in use were not a dominant theme. Most participants did not report changes in substance use; among those who did, changes were primarily decreases. Pandemic-related stress was associated with opioid use change, though direction varied. These findings suggest that stress-related responses are context-specific and may not uniformly lead to increased substance use among PWH.

Viral infections remain a global public health challenge. Stimulating the innate immune system is a potent therapeutic strategy that promotes pathogen clearance, directly impacting disease severity and clinical outcomes. Interferons and interferon-stimulated genes (ISGs) are critical components of this antiviral defense system. Neomycin, an aminoglycoside antibiotic, can induce ISG expression and help establish an antiviral state. In this study, we demonstrated that neomycin induces the production of pro-inflammatory cytokines (IL1β, TNFα, IL6, GM-CSF, and IFN-γ) in peripheral mononuclear blood cells (PBMCs) and activates key antiviral ISGs, including MxA, OAS1, and IRF7. The protein expression profiles elicited by neomycin were comparable to those induced by poly(I:C). Intranasal delivery of neomycin to CBA and BALB/c mice induced various ISGs in both the respiratory tract and splenic tissues. Prophylactic administration of neomycin significantly inhibited influenza B virus replication in the lung and nasal turbinates of CBA mice in a sublethal infection model. Overall, our data suggest that neomycin, when used prophylactically alone or combined with other antiviral strategies, shows considerable potential for the attenuation of influenza B virus infections.

Background: Patients with end-stage renal disease (ESRD) on hemodialysis are at increased risk for severe influenza, and underlying immune dysfunction may limit vaccine-induced protection. Methods: This observational open-label study evaluated immune responses in 93 hemodialysis patients vaccinated with seasonal inactivated influenza vaccine (IIV) during the 2019–2020 (n = 22) and 2023–2024 (n = 71) seasons. Immune responses were comprehensively assessed using hemagglutination inhibition and microneutralization assays to measure antibody levels, together with flow cytometry analysis of key immune cell populations, including plasmablasts, T-follicular helper cells (Tfh), and effector memory T cells (Tem). Results: During the 2019–2020 season, antibody responses in hemodialysis patients were comparable to those in healthy volunteers in both younger (18–60 years) and older (over 60) age groups. By day 7 post-vaccination, there was a pronounced increase in activated Tfh1 cells, coinciding with a surge in plasmablasts and a rise in antigen-specific B cells. This was accompanied by a T-cell response mediated by IFNγ-producing and polyfunctional CD4+ Tem cells. In the 2023–2024 season, revaccination was associated with higher baseline antibody levels but did not alter subsequent response kinetics to A/H1N1pdm, A/H3N2, and B/Yamagata antigens. In contrast, responses to B/Victoria were higher in revaccinated patients throughout the entire observation period. Conclusions: Our findings confirm that standard-dose IIV vaccination is beneficial for hemodialysis patients, inducing robust and adequate humoral and T-cell immune responses.

Background:HIV-1 infection and hazardous levels of alcohol consumption have been independently linked to gut dysbiosis affecting beneficial butyrate-producing bacteria. However, sex-based differences in the composition and function of gut microbiome of People With HIV (PWH) with a history of heavy alcohol drinking remain undetermined, which is the focus of this study. Methods:Cross-sectional study examining structural and functional features of the gut microbiome in PWH between men and women with a history of hazardous alcohol drinking recruited at St. Petersburg, Russia. 16S rDNA sequencing information was used for metataxonomic, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt2) and Linear Discriminant Analysis Effect Size (LEfSe) analyses. Group-wise comparisons were done using Mann-Whitney U-test. Further, linear and logistic regression models were used to evaluate the association between sex and measures of gut microbial dysbiosis and Firmicutes/Bacteroidota (F/B) ratio, respectively. Data were adjusted for confounding covariates particularly, HIV-viral load, Anti-retroviral Therapy (ART) and alcohol usage. Results:Metataxonomic analysis demonstrated that women depicted significantly higher microbial diversity (Operational Taxonomic Units, OTUs and Shannon Index), higher percent relative abundance (%RA) of Firmicutes, lower %RA of Bacteroidota and higher F/B ratio. Importantly, logistic regression revealed that women had twice the odds of having F/B ratio > 1. Notably, women demonstrated significantly higher %RA of butyrate-producing bacterial families, i.e., Lachnospiraceae, Oscillospiraceae, Rikenellaceae and Marinifilaceae and genera. Correspondingly, significantly greater expression of bacterial genes involved in butyrate synthesis in women was demonstrated by PICRUSt2 analysis. Additionally, women depicted lower %RA of pathobiont, Prevotellaceae particularly, Prevotella_9 genus. Conclusion:Overall, we observed significant sex-based differences in the relative abundances of beneficial bacterial communities such as butyrate producers and potential pathogenic Prevotella community in the gut microbiome of PWH with a history of heavy alcohol consumption. The observed sex-based differences are clinically relevant and could inform therapeutic strategies with evidence-based probiotics.

Relevance. The study COVID-19 is due to its continued circulation in SARS-CoV-2 in the world and the beginning of an increase cases in Russia this season. Aims. To compare the trends of the COVID-19 epidemic process in terms of morbidity and mortality in epidemic and inter-epidemic periods among the Russian population. Materials and methods. The analysis of the incidence and mortality of COVID-19 in Russia, megacities and 54 cities was carried out according to the стопкоронавирус. рф and the computer database of the Influenza Research Institute. Results. In Russia, 9 epidemics of COVID-19 and 4 inter-epidemic periods have been egistered in 5 years, the first in the summer of 2022, then in 2023, 2024 and in 2025 (from January to May). There are similar trends in reducing morbidity and mortality in epidemics and inter–epidemic periods: at the same time, the dynamics of epidemics shows an increase in morbidity in the first 5 waves, and from the sixth – a decrease, and an increase in mortality with a peak in the fourth wave, and in the fifth – a decrease in mortality to a minimum in the ninth wave. In the dynamics of epidemics in St. Petersburg, 54 cities and the Russian Federation as a whole, the coefficients of the trend of increasing morbidity were lower (k=215, k=119.3, k=87.3) than the decrease in morbidity (k = -250, k = -134.8, k = -108.5). The coefficients of the trend lines of increased mortality from COVID-19 were greater (from k = 20 to k = 162) than the decrease (from k = -15.3 to k = -29), and in interepidemic periods, morbidity (from k=-5 to k=-10.5) and mortality (from k = -1.6 to k = -19.8). The first interepidemic period was shorter and higher in morbidity and mortality than the subsequent ones. The incidence rates, as well as the coefficients of the trend lines of increased incidence, were higher in the North-Western, Far Eastern, Siberian and Ural Federal Districts than in Central, Volga, Southern, and North Caucasian. During periods of epidemics, there was a tendency for the proportion of children to increase among those who became ill, especially 7–14 years old (k = 1), and among those who died – people over 65 years old (k = 1.6), and in inter-epidemic periods, the proportion of people aged 15 –64 years (k = 2) and children 0 –2 years (k = 1.5), and among the deceased – the proportion of people aged 15–64 years (k = 2.5). Conclusions. The predominant development of the COVID-19 epidemics in the autumn-winter seasons (6 versus 3), the high intensity of the epidemics of the autumn-winter season in terms of duration and incidence over the entire period and at its peak, and the presence of 4 inter-epidemic periods (3 of them in summer) indicate the seasonal nature of the COVID-19.

Aim of the study: to assess quantitative and qualitative indicators of HIV drug resistance to antiretroviral drugs in patients with virological failure of first-line ART. Materials and methods . Clinical and laboratory parameters and results of HIV molecular genetic testing were analyzed in 964 patients with virological failure of antiretroviral therapy (ART) in 2018–2022 at the St. Petersburg AIDS Center. Fragments of the pol gene encoding HIV enzymes were examined by PCR and Sanger sequencing. Identification of HIV drug resistance mutations to antiretroviral therapy was performed using the Stanford University HIVDB algorithm Version 9.4.1. The dynamics of HIV resistance prevalence among ART recipients were assessed by comparing the results of two studies: a retrospective study (2006–2011) and a current study (2018–2022) in St. Petersburg. Results and discussion . Virological failure was associated with the development of HIV resistance mutations in 76.5% of patients. HIV resistance mutations were found in the majority of cases (93.9%) in patients receiving first-line ART. Regimens consisting of 2 nucleoside reverse transcriptase inhibitors (NRTI) + non-nucleoside reverse transcriptase inhibitors (NNRTI) combination were more frequently used (72.1%), the proportion of first-generation NNRTI class drugs was 58,7%. According to the results of HIV resistance testing, resistance to the NRTI (90.6%) and NNRTI (78.3%) classes was more common than to protease inhibitors (PI) (3.8%) and integrase strand transfer inhibitors (INSTI) (0.9%). HIV resistance to two drug classes was found in 74,2% of patients, most frequently to the NRTI+NNRTI classes (71.3%). Multidrug resistance to three drug classes (NRTI+NNRTI+PI) was rarely detected, only in 1.3% of patients. Analysis of HIV resistance to antiretroviral drugs in patients over time showed an increase in resistance to NRTIs (from 79.8% to 90.6%) and NNRTIs (from 60.4% to 78.3%), comparing the periods 2006–2011 and 2018–2022. There was also a decrease in the number of patients with resistance to PIs (from 19.9% to 3.8%). Conclusion . Our study shows that acquired HIV drug resistance was the leading cause of virological ineffectiveness of antiretroviral therapy between 2018 and 2022. Importantly, the majority of HIV drug resistance was observed in patients receiving first-line therapy. These findings highlight the need to modernize first-line ART regimens, including the wider introduction into clinical practice of drugs with a high genetic barrier to resistance. These include modern integrase inhibitors or protease inhibitors. The choice of ART regimen should be based on the patient’s previous drug history and HIV resistance indicators. When selecting a new regimen plan for patients with multidrug-resistant HIV, it is essential to use at least two or three medications (typically from different classes) that do not have any resistance mutations.

Background: Influenza viruses with truncated NS1 proteins show promise as viral vectors and candidates for mucosal universal influenza vaccines. These mutant NS1 viruses, which lack the N-terminal half of the NS1 protein (124 a.a.), are unable to antagonise the innate immune response. This creates a self-adjuvant effect enhancing heterologous protection by inducing a robust CD8+ T-cell response together with immunoregulatory mechanisms. However, the effects of NS1 modifications on T-follicular helper (Tfh) and B-cell responses remain less understood. Methods: C57bl/6 mice were immunised intranasally with 10 μL of either an influenza virus containing a truncated NS1 protein (PR8/NS124), a cold-adapted influenza virus with a full-length NS1 (caPR8/NSfull), or a wild-type virus (PR8/NSfull). Immune responses were assessed on days 8 and 28 post-immunisation by flow cytometry, ELISA, and HAI assay. Results: In this study, we demonstrate that intranasal immunisation with PR8/NS124 significantly increases tissue-resident CD4+ and CD8+ T cells in the lungs and activates Tfh cells in regional lymph nodes as early as day 8 post-immunisation. These effects are not observed in mice immunised with caPR8/NSfull or PR8/NSfull. Notably, PR8/NS124 immunisation also leads to the development of inducible bronchus-associated lymphoid tissue (iBALT) in the lungs by day 28, characterised by the presence of antigen-specific Tfh cells and GL7+Fas+ germinal centre B cells. Conclusions: Our findings further underscore the potential of NS1-truncated influenza viruses to drive robust mucosal immune responses and enhance vaccine efficacy.

Introduction. Human metapneumovirus (hMPV) holds significant epidemiological importance, being a dominant cause of lower respiratory tract infections in children under two years of age and individuals over 65. Multiple infections with hMPV throughout a person’s life are possible due to the antigenic and genetic variability of the virus. However, the genetic variability of hMPV circulating in Russia remains unexplored. Aim of the study. The aim of this study was to test a protocol for whole-genome sequencing of hMPV to assess the genetic diversity of metapneumoviruses circulating in certain regions of Russia. Materials and methods. Nasopharyngeal swabs were collected from patients of different ages with acute respiratory viral infections (ARVI) tested positive for hMPV using polymerase chain reaction (PCR). From some of the samples, viral isolates were obtained in cell culture. Whole-genome sequencing was performed on both swabs and isolates using the MiSeq Illumina platform, followed by phylogenetic analysis. Results. For the first time in Russia, whole-genome sequencing of 44 hMPV strains circulating from 2017 to 2024 was conducted. Their genetic group affiliation was described, with the A2b2 clade shown to dominate. It was confirmed that the greatest variability among genes encoding viral surface proteins was observed in the G gene, while changes in the F gene were minimal during the studied period. Conclusion. The study provides insights into the genetic diversity of hMPV strains circulating in various regions of the Russian Federation. Understanding the genetic variability of hMPV is crucial for comprehending viral evolution, transmission dynamics, and mechanisms of immune evasion, which influence the development of vaccines and antiviral drugs.

Background:Influenza is a significant public health challenge, characterized by severe disease progression and considerable societal burden. Patients at high risk of influenza-related complications require special attention in routine clinical practice. Objectives:This study aimed to compare the effects of antiviral treatments for influenza on the incidence of bacterial complications, adverse events, and disease duration in high-risk outpatients. Design:Multicenter, non-interventional, observational cohort study. Methods:The study was conducted during the 2023-2024 influenza epidemic season and included 1867 high-risk outpatients treated with oseltamivir, umifenovir, kagocel, or imidazolyl ethanamide pentanedioic acid. Results:Bacterial complications occurred in 18.87% (n = 335) of high-risk patients, with 17.41% (n = 309) requiring antibacterial therapy. The hospitalization rate was 1.24% (n = 22), and the average disease duration was 8 days. The incidence of bacterial complications varied among treatment groups: oseltamivir (18.96%, n = 102), umifenovir (12.17%%, n = 51), kagocel (22.00%%, n = 110), and imidazolyl ethanamide pentanedioic acid (22.64%%, n = 72). Adverse events were reported in 4.76% (n = 84) of patients, most commonly gastrointestinal disorders (91.67%, n = 77), followed by allergic reactions (8.33%, n = 7). The incidence of adverse events was significantly higher in the oseltamivir group compared to other treatments. Conclusion:The etiotropic agents oseltamivir and umifenovir demonstrated comparable efficacy in managing influenza in high-risk patients, as reflected by their impact on bacterial complication rates and disease duration. Both drugs may be recommended for the treatment of high-risk influenza patients.

Introduction. Optimal adherence to antiretroviral therapy (ART) is a key factor in achieving an undetectable HIV viral load (HIV VL). Among people with opioid use disorder (OUD), it is insufficient to suppress viremia. Treatment of OUD helps to increase the adherence and effectiveness of ART and HIV outcomes. The objective was to evaluate the adherence to ART in patients with HIV and OUD treated with naltrexone in oral or implantable formulations, and to compare the data obtained using the Adherence Assessment Questionnaire (AAQ), Electronic Monitoring of Treatment (EMT), and dynamic of HIV VL. Methods and materials . 200 patients with HIV infection (IV A-IV B) with OUD who completed a course of detoxification were divided into two groups (100 in each), where they received oral (ON) or implantable (IN) naltrexone treatment for 48 weeks simultaneously with ART. Outcomes of ART adherence: 1) adherence index (AI) (based on AAQ data); 2) EMT – the ratio of the number of actual openings to the number of openings to be made («correct openings»); 3) dynamic of the HIV VL level. Results. ART adherence to AI and EMT is significantly higher in patients who completed treatment with naltrexone compared with those who discontinued the treatment earlier (92.4±15.17 vs. 89.32±21.33, p<0.001 and 73.3±22.0 % vs. 65.10±32.1 %, p=0.038, respectively). A significant correlation was found between AI and EMT (r=0.78, p=0.0001); and moderate for each method with the difference in HIV VL in dynamic (AI, r=0.306, p=0.0002; EMT, r=0.305, p=0.0002). Conclusion. The stabilization of OUD remission helps to increase the ART adherence and improve the HIV outcomes. The results demonstrate the consistency of the objective and subjective methods for assessing ART adherence in patients with HIV and OUD.

The aim: to describe the duration of SARS-CoV-2 virus shedding in patients with HIV infection and to identify factors associated with prolonged viral shedding. Materials and methods: in a prospective study, the clinical and laboratory characteristics of COVID-19 and HIV infection and the duration of SARS-CoV-2 virus shedding were compared in 170 patients, titers of virus neutralizing antibodies to SARSCoV-2 were identified in 68 patients; pathogen genotyping was performed in 36 patients. Statistical analysis was carried out using the IBM SPSS Statistics package. Results and discussion: there were no significant differences in the duration of SARS-CoV-2 virus shedding in patients with varying severity grade of COVID-19; a negative relationship between the titer of virus neutralizing antibodies to SARS-CoV-2 and viral shedding duration was revealed. In 35.9% of patients (61 persons), the persistence of the virus lasted for more than 21 days, this group was characterized by an unfavorable course of HIV infection in the absence of ART, significantly lower CD4 cell values and a higher HIV viral load in the blood. Virus shedding was shown to be significantly longer in patients with B.1.1 strain versus other SARS-CoV-2 gene variants. Mutations in the Spike protein gene that increase the infectious ability of the pathogen and reduce its sensitivity to neutralizing antibodies were found in 4 patients. Conclusion: the severity of COVID-19 did not affect the duration of SARS-CoV-2 virus shedding in patients with HIV infection. Long-term persistence of the virus was discovered in patients with severe immunodeficiency (CD4<200 cl/μl) in the absence of ART. Patients with prolonged viral shedding pose an epidemiological risk in regard to developing new mutational variants of the pathogen.

Background/Objectives: Intranasal vaccination enhances protection against respiratory viruses by providing stimuli to the immune system at the primary site of infection, promoting a balanced and effective response. Influenza vectors with truncated NS1 are a promising vaccine approach that ensures a pronounced local CD8+ T-cellular immune response. Here, we describe the protective and immunomodulating properties of an influenza vector FluVec-N carrying the C-terminal fragment of the SARS-CoV-2 nucleoprotein within a truncated NS1 open reading frame. Methods: We generated several FluVec-N recombinant vectors by reverse genetics and confirmed the vector’s genetic stability, antigen expression in vitro, attenuation, and immunogenicity in a mouse model. We tested the protective potential of FluVec-N intranasal immunization in naïve mice and seropositive Th2-prone mice, primed with aluminium-adjuvanted inactivated SARS-CoV-2. Immune response in immunized and challenged mice was analyzed through serological methods and flow cytometry. Results: Double intranasal immunization of naïve mice with FluVec-N reduced weight loss and viral load in the lungs following infection with the SARS-CoV-2 beta variant. Mice primed with alum-adjuvanted inactivated coronavirus experienced substantial early weight loss and eosinophilia in the lungs during infection, demonstrating signs of enhanced disease. A single intranasal boost immunization with FluVec-N prevented the disease enhancement in primed mice by modulating the local immune response. Protection was associated with the formation of specific IgA and the early activation of virus-specific effector and resident CD8+ lymphocytes in mouse lungs. Conclusions: Our study supports the potential of immunization with influenza vector vaccines to prevent respiratory diseases and associated immunopathology.

OBJECTIVE:Many persons with opioid use disorders (OUDs) have HIV disease and experience clinically significant stress after they enroll in abstinence-based treatment and undergo medically assisted withdrawal. We examined whether opioid withdrawal affects virologic control, inflammatory markers, cognition, and mood in persons with an OUD and HIV, and explored whether measures of withdrawal stress, such as activation of the HPA axis, contribute to alterations in immune function, cognition, and mood. METHOD AND PARTICIPANTS:Study participants were 53 persons with HIV who were admitted for OUD treatment at the City Addiction Hospital in Saint Petersburg, Russian Federation. Participants were examined at admission, at the anticipated peak of withdrawal 3 to 7 days after the last day of a clonidine-based withdrawal process lasting 7 to 14 days, and 3 to 4 weeks after completing withdrawal. At these times, participants received medical exams and were evaluated for symptoms of withdrawal, as well as cognition and mood. Viral load, plasma cortisol, DHEA sulfate ester (DHEA-S), interleukin-6 (IL-6), and soluble CD14 (sCD14) were determined. Multivariable models examined the relationships between markers of HPA activation and the other parameters over time. RESULTS:HPA activation as indexed by cortisol/DHEA-S ratio increased during withdrawal, as did markers of immune activation, IL-6 and sCD14. There were no significant associations between viral load and indicators of HPA activation. In longitudinal analyses, higher cortisol/DHEA sulfate was related to worse cognition overall, and more mood disturbance. Increase in IL-6 was associated with worse cognitive performance on a learning task. There were no significant associations with sCD14. CONCLUSIONS:Worsening of cognition and measures of mood disturbance during withdrawal were associated with activation of the HPA axis and some measures of inflammation. Whether repeated episodes of opioid withdrawal have a cumulative impact on long-term HIV outcomes and neurocognition is a topic for further investigation.

BackgroundAlthough COVID-19 is primarily an acute disease, there are cases of persistent infection, primarily in immunocompromised patients. It is hypothesized that at least some variants of concern (VOCs) have arisen in such persistent cases, with the virus “spilling over” into the general population after accumulating intra-host mutations. Additionally, a growing body of evidence hints at the gastrointestinal (GI) tract as a reservoir of long-term infection, at least in some cases.ResultsWe report the genomic analysis of a highly divergent SARS-CoV-2 sample obtained in October 2022 from an HIV+ patient with presumably long-term COVID-19 infection. Phylogenetic analysis indicates that the sample is characterized by a gain of 89 mutations since divergence from its nearest sequenced neighbor, which had been collected in September 2020 and belongs to the B.1.1 lineage, largely extinct by 2022. Of these mutations, 33 were nonsynonymous and occurred in the Spike protein. Of these, 17 are lineage-defining in some VOCs or are at sites where another mutation is lineage-defining in a VOC, and/or have been shown to be involved in antibody evasion, and/or have been detected in other cases of persistent COVID-19; these include some “usual suspects,” such as Spike:L452R, E484Q, K417T, Y453F, and N460K. Molecular clock analysis indicates that mutations in this lineage accumulated at an increased rate compared with the ancestral B.1.1 strain. This increase is driven by the accumulation of non-synonymous mutations, with an average dN/dS value of 2.2, indicating strong positive selection during within-patient evolution. Additionally, the presence of mutations that are rare in the general population samples but common in samples from wastewater suggests that the virus had persisted for at least some time in the GI tract.ConclusionsOur analysis adds to the growing body of evidence that the evolution of SARS-CoV-2 in chronically infected patients can be a major source of novel epidemiologically important variants and points to the potential role of the GI tract in long-term infection.

The literature review is devoted to human herpes viruses 6 and 7 (HHV-6, HHV-7). The history of the study of exanthem subitum, the discovery of HHV-7, HHV-6 and its types, epidemiology, pathogenesis, stages of infection, clinical features, laboratory diagnosis and treatment are discussed. Despite some progress in the study of HHV-6 and HHV-7, many aspects of their pathogenesis, their relationship to human pathology, and issues of diagnosis and therapy remain unclear. This is manifested by both under-diagnosis of acute forms of the disease and overdiagnosis of latent infection as acute, which leads to irrational therapy of patients. Further research in this area is needed.

The purpose. To assess the prevalence of HIV-1 drug resistance and multidrug resistance to antiretroviral drugs in adult patients with and without treatment experience in Russia in 2024–2025. Materials and Methods. A total of 1888 plasma samples from adult HIV-infected patients from 21 regions of Russia were analyzed. The average age of the patients was 42,08 years; 60,86% were men and 39,14% were women. 77,65% of patients had information about treatment experience; 28,04% of these patients were treatment-naive and 71,96% were treatment-experienced. Consensus nucleotide sequences of the pol gene, encoding HIV-1 protease, reverse transcriptase, and integrase, were obtained using next-generation sequencing. HIV-1 drug resistance analysis was conducted using the Stanford University HIVdb database. Results. The most common HIV-1 surveillance mutations were substitutions in the reverse transcriptase – M184V and K103N. In treatment-experienced patients, high levels of HIV-1 resistance were observed to NNRTIs (efavirenz) and NRTIs (lamivudine, abacavir), and in treatment-naive patients – to NNRTIs (efavirenz, nevirapine, rilpivirine). Low levels of HIV-1 resistance were observed to protease and integrase inhibitors, including dolutegravir. The most common combinations of surveillance mutations in treatment-experienced patients were G190S + K101E, G190S + M184V, K65R + M184V, K103N + M184V and G190S + K65R + Y181C. The most common combination of HIV-1 multidrug resistance was NRTI + NNRTI resistance. Conclusion. Early detection of drug resistance mutations using next-generation sequencing (NGS) followed by quasispecies analysis can significantly change the approach to choosing first- and subsequent-line etiotropic treatment regimens and improve the clinical and cost-effectiveness of HIV-1 treatment.

Background: Cigarette smoking has been associated with liver fibrosis in the setting of hepatitis C virus (HCV) infection but has not been studied among people with HIV (PWH) who consume alcohol. Methods: This is a cross-sectional study of PWH with heavy drinking and daily smoking in St. Petersburg, Russia. The primary independent variable was past 30-day cigarettes per day (cpd), and the secondary independent variable was pack-years at study entry. Advanced liver fibrosis was defined as FIB-4 > 3.25. Analyses were adjusted for gender, body mass index (BMI), past 30-day number of heavy drinking days, HCV and CD4 count. Results: Participants (n = 400) were two-thirds male (67.3%), young (median age 38 years), lean (median BMI 22), HCV antibody positive (84.5%) and not severely immune suppressed (median CD4 count 351). The median number of past-month cpd was 20 (IQR: 15–25), and the median pack-years was 24 (IQR: 17–31.8). The prevalence of advanced liver fibrosis was 11.3% (45/400). In the adjusted logistic regression analyses, we did not observe a significant association between cpd [middle (10.1–20 cigarettes) vs. lowest (5–10 cigarettes) category (adjusted odds ratio [aOR] (95% confidence interval [CI]): 1.06 (0.40–2.83), highest (>20.0 cigarettes) vs. lowest category aOR (95% CI): 0.65 (0.21–1.99), global p-value = 0.62]. The secondary analysis with pack-years yielded similar results [middle (20.1–30 pack-years) vs. lowest category (≤20 pack-years) aOR (95% CI): 0.81 (0.33–1.99), highest category (>30 pack-years) vs. lowest category aOR (95% CI): 0.91 (0.38–2.19); global p-value = 0.58]. Conclusions: In this Russian cohort of PWH, we did not detect an association between recent cigarette use or mean pack-years and advanced liver fibrosis.