The aim . To study clinical, epidemiological and laboratory indicators of treatment efficacy of viral hepatitis C in HIV-infected patients in the Novgorod region. Materials and methods . The data of primary medical records of HIV-infected patients living in the territory of the Novgorod region with viral hepatitis C co-infection were used for the analysis. The study group included 142 patients receiving hepatitis C treatment from 2014 to 2023. The time of the start of receiving hepatitis C antiviral therapy and duration of treatment, the time of onset of sustained virological response, the hepatitis C antiviral therapy regimen used, the presence and stage of liver fibrosis, the dynamics of biochemical and immunological indices, as well as the antiretroviral therapy regimen used during the period of hepatitis C virus treatment were studied. Quartile methods and methods of statistical significance assessment were used for statistical processing. Results and discussion . Of the subjects, 61% (87 people) were males and 39% (55 people) were females. The most frequent genotype of hepatitis C virus in Novgorod region during the period under study was genotype 1b (40.1% of cases) and 3a (30.3% of cases). Patients with fibrosis degree F3 (24%) and F4 (18%) prevailed in the study group. The distribution of fibrosis degrees F0–F2 was uniform (11–15%). In the studied group of patients, the time interval between the detection of antibodies to hepatitis C (ELISA) and the immediate initiation of antiviral therapy averaged from 1 to 10 years. Sustained virological response by 12 weeks from the start of antiviral therapy was achieved in 94% of cases. There were 4 cases (3%) of ineffectiveness of antiviral therapy of viral hepatitis C. In patients after the start of treatment after one month there was a significant decrease in ALT and AST enzymes (from median values of 70.5 and 51.9, respectively, to median values of 28.8 and 30.0, respectively) with preservation of these values until the end of antiviral therapy and control time (after 12 weeks and 24 weeks, respectively). Conclusions . The most frequent hepatitis C genotypes in HIV-infected patients in Novgorod region are 1b and 3a. At the time of treatment initiation, the majority of those studied already had fibrosis stage F3 or F4 (according to METAVIR). The used schemes of viral hepatitis treatment showed high efficiency with achievement of stable virological response at the 12th week of therapy (in 4 studied cases virological ineffectiveness was noted with subsequent replacement of several PVT schemes) and stabilisation of liver metabolic processes.

The aim . To clarify the effectiveness of treatment for newly diagnosed and relapsed tuberculosis combined with HIV infection in patients in places of imprisonment. Materials and methods . 327 patients (men) with tuberculosis and HIV infection stages 4B, 4C and 5: Group 1 — 72.2% (n=262) with newly diagnosed tuberculosis, Group 2 — 17.9% (n=65) with relapse. To analyze the effectiveness of treatment, χ 2 was calculated with Yates correction for continuity between the indicators of the groups by treatment quarters. Results and discussion . In the first 3 months of treatment, bacterial excretion by sputum microscopy ceased in 41.7% (48/115) and 33.3% (11/33), in the 12th month of treatment in 63.5% (73/115) and 57.6% (19/33); in the first 3 months of treatment, bacterial excretion by sputum culture ceased in 42.4% (72/170) and 42.0% (21/50), in the 12 th month of treatment in 67.6% (115/170) and 62.0% (31/50); In the first 3 months of treatment, closure of decay cavities occurs in 26.5% (31/117) and 26.7% (12/45), in the 12 th month of treatment in 64.1% (75/117) and 55.6% (25/45) of newly diagnosed tuberculosis, respectively. Conclusion . In patients with tuberculosis combined with HIV infection in an anti-tuberculosis institution of the penitentiary service of Russia, the effectiveness of treatment for newly diagnosed and relapsed disease is practically the same.

Sexually transmitted infections (STIs) are prevalent worldwide and pose a significant challenge to national healthcare systems. Human papillomavirus (HPV) annually causes over 600,000 cases and 350,000 deaths from cervical cancer (CC). Coinfections with HPV and other STIs often potentiate the development of dysplastic processes and CC. The role of STI and HPV coinfection in carcinogenesis and the impact of multiple HPV infections on the development of CC have been poorly studied. Aim of the study : to assess the prevalence and risks of carcinogenesis in various variants of coinfection with human papillomavirus and other sexually transmitted infection agents. Materials and methods . A total of 9,310 HPV-positive women with STIs and/or other diseases were examined. Detection of 14 HPV genotypes was performed using PCR. The diagnosis of cervical intraepithelial neoplasia (CIN) was established based on extended colposcopy and cytological examination. Methods: PCR, clinical, epidemiological, and statistical methods. Results and discussion . In case of coinfection with STIs, the prevalence of HPV genotypes 16, 18, and 45 had statistically significant differences (32.0%, 9.7%, and 11.4%, respectively, p<0.001). The prevalence of HPV type 16 was characterized by an asymmetric distribution between STIs, demonstrating maximum values for urogenital candidiasis, anogenital warts, and chlamydial infection (40.7–36.8%) and lower values for anogenital herpes and cytomegalovirus infection (28.3–26.8%, p=0.02). The prevalence of CIN in the group of patients with STIs (11.8%) significantly exceeded the indicator in all examined patients (5.0%, p<0.001). The combination of STIs with a single HPV type was the most common coinfection (92%). The presence of multiple HPV infections during coinfection with STIs in patients in the study group did not increase the risk or severity of CIN (p>0.05). Conclusion . The prevalence of HPV among patients with STIs (30.7%) was significantly higher than in the comparison group (p<0.001). In HPV and STI coinfections, a high prevalence of HPV type 16 (25–40.7%) and CIN of varying severity (3.7–16.7%) was observed. A potentially high risk of carcinogenesis cannot be excluded in cases of HPV coinfections with mycoureaplasmosis and anogenital herpes infection due to the significant prevalence of CIN (12.1–14.1%), comparable to the prevalence of CIN in chlamydial infection (16.7%, p>0.05). The obtained results are consistent with existing data on the negative impact of the association of HPV and chlamydial infection on the risk of neoplasia development and complement the existing knowledge base in terms of assessing the impact of HPV coinfections with mycoureaplasmosis, anogenital herpes, anogenital warts, as well as multiple HPV infections on the risk of carcinogenesis.

The aim of this study was a systematic in silico evaluation of the effect of natural missense mutations in PNOC on the stability and binding energy of its complexes with CCR5 and CXCR4 to identify variants with enhanced affinity, potentially suitable for inhibiting viral entry. Materials and methods . Three-dimensional structures of wild-type PNOC protein complexes with CCR5 and CXCR4 were built using molecular modeling methods with the AlphaFold algorithm. Based on these, mutant PNOC variants localized at the receptor contact sites were modeled using the FoldX program. To quantitatively assess the mutation effects, we calculated the change in the complex stability free energy (∆Stability) and the protein-protein interaction energy (∆Connection), analyzed the change in the number of atomic contacts (∆Contacts), and predicted the functional impact of the substitutions using the PolyPhen-2 algorithm. Results and discussion . The wild-type PNOC was shown to have a higher predicted affinity for CXCR4 compared to CCR5. For the PNOC-CCR5 complex, one candidate (E50K) was identified that fully met the strict selection criteria (decrease in both ∆Stability and ∆Connection, preserved number of contacts, «benign» status). For the PNOC-CXCR4 complex, a broader spectrum of significant mutations was revealed, among which four (F14L, S20N, R23K, V43M) met all the criteria. Mutations with selective action are of particular interest: E50K (improves binding to CCR5 but impairs it for CXCR4) and F14L (the only mutation that improves binding parameters for both receptors). Conclusion . For the first time, a systematic computational analysis of the impact of PNOC missense mutations on its interaction with HIV-1 co-receptors has been conducted. Specific amino acid substitutions (E50K for CCR5; F14L, Q22P, and others for CXCR4) that statistically significantly improve the binding energy and complex stability have been identified. These mutant PNOC forms represent promising candidates for further experimental validation of their ability to inhibit viral binding to the target cell and can be considered as a basis for developing new strategies for antiviral therapy.

The aim : to study the effectiveness of repeated chemotherapy courses after ineffective courses. Materials and methods . A retrospective documentary study of the general population (n=817) of all registered newly diagnosed cases of tuberculosis in the Kaluga region in 2019–2023 was conducted. Two groups of patients were compared: patients with an effective outcome of chemotherapy (group 1, n=560) and patients with an ineffective outcome of chemotherapy, for whom the repeated course was effective (group 2, n=72). Results and discussion . A high risk of registering an ineffective course of chemotherapy and prescribing a repeated course is noted in unemployed patients (52.8% versus 38%, p=0.0158) and homeless persons (11.1% versus 2.9%, p=0.003). Among patients with an ineffective chemotherapy course and a repeated effective one (group 2), bacterial excretion (91.7% versus 49.3%, p<0.001) and lung tissue decay (86.1% versus 37.5%, p<0.001) are significantly more common. At the same time, the presence of MDR and XDR pathogens, as well as the presence of HIV infection, do not have a significant impact on the registration of an ineffective chemotherapy course (p>0.05). Among patients with DS-TB and MDR-TB in the group with an effective chemotherapy course after an ineffective one (Group 2), bacterial excretion lasts longer (3 months versus 1 month and 2 months versus 10 months, respectively, p<0.001), which determines an increase in the duration of treatment (16 months versus 9 months and 36.80±15.75 versus 19.91±3.85 months, p<0.001). Conclusion . The obtained results show that the duration of bacterial excretion has a significant impact on the duration and effective outcome of TB chemotherapy in patients with both DS-TB and MDR-TB.

Aim of the study : To establish the incidence of opportunistic infections (OI) in patients with HIV/tuberculosis co-infection depending on the severity of immunosuppression and to evaluate the role of endoscopy in the diagnosis of concomitant diseases. Materials and methods : A retrospective analysis was performed of the inpatient medical records of 170 patients with HIV/tuberculosis co-infection in 2023 who underwent diagnostic bronchoscopy and esophagogastroduodenoscopy with sampling for the diagnosis of OI. Results : The spectrum and frequency of occurrence of concomitant OIs, except for tuberculosis, were as follows:esophageal candidiasis in 37 patients (21.8%), CMV infection in 24 patients (14.2%), Pneumocystis pneumonia in 6 patients (3.6%), mycobacteriosis in 4 patients (2.4%), Kaposi's sarcoma in 4 patients (2.4%), and CNS toxoplasmosis in 2 patients (1.2%). The sensitivity and specificity of endoscopic biopsy for the diagnosis of esophageal candidiasis was 100%; Pneumocystis pneumonia and pulmonary mycobacteriosis were verified in 100% of cases using bronchoalveolar lavage. A comparative analysis of the frequency of secondary infectious lesions depending on the form of pulmonary tuberculosis showed that patients with disseminated tuberculosis were more often diagnosed with esophageal candidiasis (36.1% of cases, p=0.005), while patients with disseminated tuberculosis and caseous pneumonia were significantly more likely to have manifest CMV infection (13.9% and 50%, respectively, p=0.006).An analysis of the incidence of concomitant diseases in patients with different numbers of CD4 lymphocytes in the blood showed a significant predominance of esophageal candidiasis (p<0.001) and manifest CMV infection (p=0.01) in patients with immunosuppression, while in patients with CNS toxoplasmosis, Kaposi's sarcoma, nontuberculous mycobacteria, Pneumocystis pneumonia and active CMV infection no differences in the frequency of detection were obtained (p>0.05). Conclusions : Thus, endoscopic diagnostic methods have great diagnostic value for identifying acute respiratory infections in patients with HIV/tuberculosis coinfection. Disseminated pulmonary tuberculosis was a significant predictor of the development of such acute respiratory infections as esophageal candidiasis, overt CMV infection, Pneumocystis pneumonia, and mycobacteriosis in patients with late-stage HIV infection.With a decreased CD4 count, the most common findings during examination were candidiasis and overt CMV infection.

The relevance of HIV infection is clear due to the steady increase in the number of people living with HIV (PLHIV). The aim: To present a clinical case of nephronephrosis in a patient with renal AA amyloidosis and HIV infection following COVID-19. Materials and methods . In this clinical case, a patient with HIV infection (CD4 lymphocyte count of 420 cells/mL) developed bilateral nephronephrosis with acute renal failure. Signs of acute kidney injury were observed: proximal and distal tubular epithelium with karyolysis, and the cytoplasm of some cells was coagulated. Results and discussion . A possible cause of acute kidney injury could be a previous COVID-19 infection one month prior to hospitalization. Although the patient had no previous complaints, traces of protein were present in a urinalysis. COVID-19 patients experience a cytokine storm, disrupting the function of all organs, including the kidneys. These disruptions often persist even after the symptoms of coronavirus infection resolve. Conclusion : COVID-19 infection should likely be considered an additional risk factor for kidney damage in HIV-infected patients.

The aim : to perform surveillance over HIV-1 drug resistance mutations among people living with HIV without history of antiretroviral therapy as well as among those receiving antiretroviral treatment and residing in different territories of the Far Eastern Federal district. Materials and methods . A total number of 420 patients diagnosed with HIV-infection and residing in 8 constituent entities of the Far Eastern Federal district were examined. «AmpliSense® HIV-Resist-Seq» kit was used to perform sequencing of the amplified fragments of HIV-1 pol-gene coding protease and a part of reverse transcriptase to detect drug resistance mutations. Stanford University HIVdb Program was employed to retrieve information on drug-resistance mutations. Results and discussion : sub-subtype A6, which is prevalent in Russia, was also dominant in the surveyed group of patients and was isolated in 282 cases (67.1%). A total number of 49 samples were typed as subtype B (11.7%), 12 samples as subtype C (2.9%), 4 samples as subtype G (1.0%). Subtype A7 (0.2%) was detected in one patient from the Republic of Sakha (Yakutia). Different recombinant forms of the virus were identified in 72 patients (17.1%). Percentage of recombinant forms derived from subtypes A and G totaled 80.6% (n=58). Surveillance drug resistance mutations were revealed in 108 out of 248 patients undergoing antiretroviral treatment (43.5%) and in 6 out of 172 treatment-naïve patients (3.5%). Drug resistance to non-nucleoside inhibitors of reverse transcriptase drugs was most common in both treatment naïve patients and those with a prior experience of antiretroviral therapy. Conclusion : regular surveillance of acquired drug resistance provides insight into the effectiveness of HIV prevention and treatment programs in the constituent entities of the Russian Federation and will allow the development of recommendations for treatment strategies.

Aim : to conduct a prospective analysis of the medical history and management tactics of a patient with meningoencephalitis on the background of HIV infection. Materials and methods . A patient with HIV infection who was hospitalized in the infectious diseases department of the Melitopol Regional Hospital was under dynamic supervision. The patient was managed in accordance with clinical symptoms (treatment of meningoencephalitis) and national clinical guidelines (treatment of patients with HIV infection). The results of the survey were discussed with the participation of related specialists. Result and its discussion . HIV infection in a patient who does not receive ART can occur with numerous complications. Despite the search for an infectious agent, a comprehensive examination of the patient failed to identify the causative agent of meningoencephalitis. The patient’s neurological symptoms could not be eliminated, but his general condition improved during treatment. Conclusion . Increasing adherence to ART therapy is a key task in the prevention of secondary complications in patients with HIV infection. It is necessary to expand the range of laboratory techniques that make it possible to identify the maximum possible number of potential pathogens of purulent-septic brain infections in daily clinical practice.

The aim of this study was to investigate risk factors that influence the epidemic effectiveness of antiretroviral therapy. Materials and methods . Data on incidence, prevalence, mortality, the number of new HIV infections, the number of deaths from HIV-infected individuals, the number of people living with HIV (PLHIV), the number of patients receiving antiretroviral therapy (ART), and viral load (VL) and immune status (IS) testing results were analyzed. Results and discussion . Antiretroviral therapy has been used in the Vologda Oblast for 19 years and, in 2023, covers 82.1% of the total number of people living with HIV and 86.1% of patients registered for dispensary care. Based on an analysis conducted in the region between 2005 and 2023, the number of people living with HIV increased by 4.1 times, while the number of patients registered for follow-up care increased by 5.5 times. All patients were eligible for treatment monitoring, and 94.8% were tested for viral load. During this period, a positive impact of antiretroviral therapy on the HIV epidemic has been observed, as evidenced by a decrease in the number of new cases and the number of patients not registered for follow-up care. It is also worth noting the increase in the proportion of patients in the clinical manifestation stage, which increased from 25% to 50%. The effectiveness of ART is negatively impacted by factors including incomplete ART coverage among PLHIV under clinical observation (86.1%), a long period of therapy initiation from diagnosis (averaging 358 days), non-adherence to therapy among PLHIV (33.1%), and the achievement of an undetectable viral load in only 80.8% of PLHIV. Conclusion . An analysis of the development of HIV infection in the Vologda Oblast demonstrates a positive impact of the widespread use of antiretroviral therapy on the incidence rate, with stabilization noted. Currently, the epidemic can be classified as developing severe and comorbid forms of HIV. No reduction in HIV-related mortality has been observed with the use of antiretroviral therapy. Even with full treatment coverage, comprehensive organizational and preventive programs are necessary to impact the epidemic.