EDITORIAL
Aim: to show the importance of the features of the development of Hodgkin’s lymphoma (HL) against the background of HIV infection, possible clinical relationships and consequences of simultaneous diseases in patients, as well as complex therapy.
Material and methods. The article presents an analytical review of the problem and retrospective data on 63 patients with HIV[1]associated HL (HIV-HL) who were diagnosed with HL in St. Petersburg hospitals in the period 2000–2017. For the diagnosis of HIV-HL, regulated morphological, immunohistochemical, instrumental and laboratory research methods were used, the tumor stage was determined based on the Cotswolds-modified Ann Arbor classification. The diagnosis of HIV infection was confirmed by the detection of specific antibodies to HIV (and the p24 antigen) during serological and enzyme immunoassay of blood, by immune blotting. The number of copies of HIV RNA and the number of CD4 lymphocytes in the blood of patients were determined using commercial test systems approved for use in the territory of the Russian Federation. The analysis of overall survival was performed using the Kaplan–Meyer method. Statistical processing of the research results was performed using statistical programs MS Excel 2010, GraphPad Prism 8 (GraphPad Software, Inc., USA), SPSS version 22.
Results. The study group was dominated by men (73%), the median age was 32 years, in 16 (25.4%) patients HIV and HL were detected simultaneously. The number of CD4 lymphocytes > 500 cl/μl at the HL debut was noted in 33.3% of patients, patients with severe immunosuppression prevailed (50–250 cl/μl in 20 (31.7%), 250–500 cl/μl in 11 (17.5%), less than 50 cl/μl in 11 (17.5%). The amount of HIV RNA>400 kop/ml was noted in 82.5%, HIV infection at stages 4B-5 was detected in 89% of cases, at the time of detection of HL ART was performed in 16 patients. EBV coinfection (77.8%), cytomegalovirus (60%), viral hepatitis (55.6%) with a predominance of viral hepatitis C, common opportunistic infections (tuberculosis, pneumocystis pneumonia, toxoplasmosis of the brain, common candidiasis), simultaneously occurring from 1 to 3 infections were observed in 77.8%. Stage IV HL was established in 54%, III — in 22%, II — in 24% of patients, the presence of B-symptoms was confirmed in 73% of cases. The predominant histological variant of HIV-HL was nodular sclerosis (58 patients), mixed[1]cell sclerosis in 4 patients, with lymphoid predominance in 1 case. Extranodal lesions were observed in 34 (54%), complications of the tumor process in 33 (37.5%) patients. 42 (66.7%) patients received antitumor treatment for HL: line 1 according to the ABVD scheme — 85.7% (80% achieved PET-negative complete remission (CR), according to the VEASORR esc or VEASORR schemes — 33.3%; line 2 — according to the ICE or DHAP schemes (n=10). An objective response was noted in 4 patients, PET-negative response in 2 of them, partial PET-positive regression in 2 patients. Progression was observed in 2 people. Autologous bone marrow transplantation was performed in 2 patients (in partial PET-positive regression); line 3 (n=3) — chemoimmunotherapy with bendamustine, gemcitabine (2 patients underwent autologous bone marrow transplantation). The cumulative life expectancy of patients for 1 year and 2 years was 44% and 37%, respectively, 1-year overall survival was 75%, 2-year — 60%. The factors negatively affecting survival and life expectancy were tumor progression and complications, ECOG≥2 (p=0.0001), candidiasis, pneumonia (p=0.001), viral hepatitis B and C (p=0.045), lack of antitumor treatment and ART (p=0.0001), age younger than 40 years, central nervous system damage, the presence of 1 or more concomitant infections (p=0.024).
Conclusion. HIV-HL is one of the most common hematological malignancies, characterized by heterogeneity in its manifestations, polymorphism of pathogenetic and clinical features and relationships. During the dispensary supervision of PLHIV, special attention should be paid to the factors of an unfavorable prognosis of the disease, the timeliness of the appointment of ART and the assessment of the risks of developing lymphoproliferative diseases within the framework of the immune system restoration syndrome (IRIS) in order to increase their survival and quality of life. Further research is needed on the pathogenesis, early diagnosis and effective treatment of lymphomas associated with the human immunodeficiency virus
ANALYTICAL REVIEW
Despite the measures taken by WHO to combat tuberculosis, the level of morbidity and mortality from it throughout the world still remains quite high. The effectiveness of treatment also does not reach the target indicators, which forces TB specialists to wonder about the reasons for the ineffectiveness of the treatment and ways to solve them. The medical and social characteristics of patients and their personal characteristics certainly influence the therapy and adherence to it, and subsequently its effective[1]ness and the outcome of the disease. At present, a holistic psychosocial portrait of a patient with tuberculosis, including those combined with HIV infection, has not yet been developed. Knowledge of the psychological and social characteristics of tuberculosis patients will allow us to identify their personal characteristics and existing problems, which will further allow them to carry out psychological adaptation of the therapy at all stages of treatment.
ORIGINAL STUDIES
Aim. Determination of the causes of deaths and analysis of the survival of people living with HIV, depending on an adherence to dispensary observation and treatment.
Materials and methods. The analysis of socio-demographic characteristics and clinical and laboratory data of 284 adult HIV patients observed in 1999–2011 at the Lomonosov Interdistrict Hospital named after I. N. Yudchenko was carried out. Patients who followed the prescribed monitoring regimen (at least 2 times a doctor’s visit during the year) were considered committed to dispensary supervision. Patients who observed the regularity and continuity of monitoring and receiving antiretroviral therapy (ART) were considered committed to treatment. Among the patients included in the study, 115 people were committed to treatment or follow-up and 169 patients were non-committed. Objective (biological) indicators of adherence and effectiveness of treatmentwere the number of CD4 lymphocytes and the level of HIV viral load. Based on the method of comparing survival curves, factors related to the life expectancy of HIV patients were assessed, taking into account the gender of patients, their adherence to monitoring and treatment, indicators of HIV viral load and the number of CD4 lymphocytes and the outcome of the disease from the moment of registration at the dispensary and over the next 120 months (after 3 months, 6 months, 1.5 years, 2 years, 5, 7 and 10 years).
Results and discussion. Significant differences were found in the survival curves of patients who received and did not receive ART (117.9 and 91.4 months, p<0.005) and patients who were committed and non-committed to therapy (116.9 and 83.8 months, p<0.005). Regardless of adherence to outpatient follow-up and therapy, the survival time of women compared to men for the entire follow-up period was longer (105.0 and 92.4 months, respectively, p<0.005). Among those committed to treatment, 21% of patients died due to concomitant somatic pathology, 5% from injuries incompatible with life. In the group of those committedto follow–up, the causes of deaths in 12% were various somatic pathology, brain lymphoma — in 1% and injuries incompatible with life — in 3% of cases. The highest mortality rates were recorded among patients who were not exposed to ART (71%) and the routine of follow-up (52%). Almost half of these patients (49%) died from secondary HIV infections, of which 85% of cases were posthumously diagnosed with tuberculosis, mainly the pulmonary form of the disease. The second most common cause of death was violent death, including drug poisoning.
Conclusion. Regular dispensary observation, timely initiation of ART and adherence to therapy make it possible to control the disease, prevent the development of opportunistic pathology, and improve the quality and life expectancy of patients with HIV infection. Despite the increased availability of ART and strategies for active involvement and retention of patients in dispensary care, issues of patient adherence to therapy remain key in the management of HIV patients.
EPIDEMIOLOGY
The aim of the study: to analyse diagnostic trends of HIV-infection in the Russian Federation in the period 2017–2022.
Materials and methods. The study used data obtained from reports from the Federal Register of persons infected with the human immunodeficiency virus (FRHIV). The circumstances in HIV diagnosis and clinical and epidemiological characteristics of newly diagnosed patients, including CD4+ T-lymphocyte counts, were analysed. A likely time window between presumed infection and confirmation of HIV diagnosis was also determined. Categorical data evaluated in the study were presented as proportions and caparisoned using the chi-square test (χ2). In case of multiple comparisons, the Bonferroni correction for multiplicity was used. Quantitative data were tested for normality using the Kolmogorov-Smirnov criterion. In most cases, nonparametric characteristics of distributions — median and interquartile range — were applied, as well as the Mann-Whitney criteria for comparison of two independent groups and the Kraskell-Wallis criteria for comparison more than two groups, followed by pair wise comparisons using the Mann-Whitney criterion with Bonferroni multiplicity correction. A p-value<0.05 was considered statistically significant. Data analysis and graphical visualization was performed using the statistical software R version 4.1.1 and its libraries.
Results and discussion. The results showed an increase in HIV detection through voluntary testing, preventive medical examination, and clinical indications. The proportion of injecting drug users (IDUs) decreased over time, while the involvement of women in the epidemic process and heterosexual transmission increased. Additionally, there was an increase in the proportion of patients aged 35 years and older. The analysis of CD4-cell counts revealed significant differences among gender and age subgroups. Women had higher absolute CD4-lymphocyte counts throughout the follow-up period. Patients aged 0–14 years had the highest proportion of CD4-lymphocytes over 500 cells/μL, while patients over 50 years old had the highest proportion of CD4-lymphocytes less than 200 cells/μL. Men who have sex with men and people infected through mother-to-child transmission had the highest mean baseline CD4-cell counts. IDUs and heterosexuals had a statistically significant decrease in CD4-cell counts over the follow-up period and also had the longest median time from infection to disease detection — 24 and 20 months, respectively.
Conclusion: Thus, this study helps identify the most significant risk groups of HIV-infected individuals in Russia at present.
The high level of hepatitis B and C infection in the modern period in the general population increases the frequency of contact of hospital specialists with patients with this infectious pathology. A significant concentration of infection sources in medical organizations and violations in the implementation of disinfection and sterilization algorithms and requirements for hand hygiene of medical workers create conditions for the nosocomial spread of viral hepatitis pathogens with a contact transmission echanism.
The aim. Substantiation of the main directions of prevention of occupational infection viral hepatitis with a contact transmission mechanism in hospitals of Saint Petersburg.
Materials and methods. A retrospective epidemiological analysis of the annual reports of Saint-Petersburg hospitals was carried out, which contain information on the number of new cases chronic forms of viral hepatitis among specialists of medical organizations and on the number personnel under dispensary supervision for these infectious diseases, as well as on the number of injuries received by hospital staff while performing functional duties, as well as vaccination coverage against viral hepatitis B, measles and diphtheria for the period from 2009 to 2022. The assessment of the equipment of megapolis healthcare institutions modern washing-disinfecting and sterilization equipment was also carried out.
Results and discussion. The realization of the possibility of infecting hospital specialists viral hepatitis with a contact transmission mechanism is predetermined by the high concentration of patients with this pathology in healthcare institutions; the presence of occupational injuries during the implementation of medical and diagnostic procedures and disinfection and sterilization measures.
Conclusion. A set of measures for early detection of sources of infections with a contact transmission mechanism among patients and staff; disinfection of medical devices using modern disinfection and sterilization equipment; revaccination against hepatitis B and equipping workplaces of specialists with personal protective equipment in full remains relevant for the prevention of occupational infection of medical workers.
CLINICAL PRACTICE
Aim: to conduct a clinical and epidemiological analysis of cases of central pontine myelinolysis (CPM) in HIV-infected patients. Materials and methods. Four patients hospitalized in the infectious diseases department of No. 1 Clinic of the South Ural State Medical University were under dynamic observation. Results and its discussion. Four patients hospitalized in the infectious diseases department of Clinic No. 1 of the South Ural State Medical University were under dynamic observation. Patient management was carried out in accordance with current clinical recommendations for the provision of medical care to patients with HIV infection with a set of clinical and laboratory methods, including examination of lumbar puncture, its cytological and biochemical composition, determination of DNA of cytomegalovirus (CMV) and Epstein-Barr viruses (EBV) herpes simplex types 1 and 2, T. gondii, Cr. Neoformans, M. Tuberculosis, Cryptococcus neoformans, the presence of pathogens of bacterial infections. All patients underwent magnetic resonance imaging (MRI) of the brain. Conclusion. The process of demyelination of the central nervous system develops regardless of the level of CD4 lymphocytes and HIV viral load. The main method for verifying the diagnosis is MRI of the brain
The aim is to present the results of the anamnesis, diagnosis and treatment of a case of a combination of malignant melanoma of the skin and basal cell carcinoma of the skin in a patient with HIV infection. Material and methods. The clinical observation of the development of multiple skin lesions with malignant neoplasms (melanoma and basal cell carcinoma) against the background of HIV infection in a patient with low adherence to follow-up and antiretroviral therapy (ART) is described. Clinical and anamnestic data, results of examination and therapy are presented. Results and discussion. Malignant neoplasms of the patient’s skin were first identified by a dermatovenerologist. The patient was routed to an oncologist, fully examined and successfully treated with a combined method (surgical removal of tumors, photodynamic therapy and immunotherapy). Further observation and examination revealed the metastasis of melanoma. The above observation indicates the need for timely and comprehensive examination of people living with HIV (PLHIV) for early detection of oncological diseases. The case demonstrates the possibility of obtaining effective treatment of a malignant neoplasm of the skin against the background of immunosuppression in the short term, despite the patient’s low adherence to therapy. Conclusion. It is especially important for outpatient doctors (infectious disease specialists, dermatovenerologists, surgeons, etc.) to be oncological when working with PLHIV. It is necessary to include malignant neoplasms of the skin, including melanoma and basal cell carcinoma, in the range of differential diagnostic search for erosive ulcerative and nodular lesions. The presented case highlights the need for timely provision of comprehensive medical care and proper routing of comorbid patients.
Relevance. HIV infection is a chronic sexually transmitted infectious disease. Given the single route of transmission, quite often HIV-infected patients develop a syphilitic infection. At the same time, syphilis against the background of HIV infection has its own clinical characteristics. It is important for doctors of various specialties to know these features.
Description of the case. A clinical case of secondary syphilis and early neurosyphilis in a 52-year-old patient with HIV infection is presented.
Discussion. Patients with HIV infection are characterized by unusual clinical manifestations of syphilis in the form of its malignity, atypical, severe course with the development of various complications. In the article, the authors describe atypical manifestations of papular syphilide of the palms and soles. The effectiveness of specific treatment has been shown.
Conclusions. Doctors’ knowledge of the clinical features of syphilis against the background of HIV infection will allow them to avoid diagnostic errors leading to late treatment and the development of complications.