The lecture, based on international and our own scientific and clinical experience, examines aspects of epidemiology, features of clinical manifestations, diagnostics, and treatment of HIV infection in children. It covers complex issues related to the study of adverse events associated with the use of antiretroviral drugs, disorders of various organs and systems directly or indirectly related to the effects of HIV, drugs, and comorbid pathological processes. It presents materials related to the problem of cardiovascular diseases, the risk of which in children increases with age, the duration of HIV infection, and the duration of antiretroviral therapy. It emphasizes the importance of metabolic disorders (impaired lipid and glucose metabolism), the role of endothelial cell damage and dysfunction of the vascular endothelium of the heart and brain in the early development of cardiovascular diseases in children, and proposes an algorithm for providing assistance to children with HIV infection and dyslipidemia during antiretroviral therapy. The lecture is intended for a wide range of specialists, residents, and students of medical universities.
The aim . To determine the HIV-1 drug resistance profile in patients with virological failure to elsulfavirine-containing antiretroviral therapy in a real-world clinical setting. Materials and methods . The study group consisted of HIV-1 nucleotide sequences ( pol gene fragments encoding protease and part of reverse transcriptase) from 179 HIV-infected patients with virological failure of elsulfavirine-containing antiretroviral therapy and who had not previously received other non-nucleoside reverse transcriptase inhibitors. Resistance mutations were identified and HIV-1 drug resistance was determined using the HIVdb database (v. 9.8). Results and discussion . HIV-1 mutations associated with viral resistance to non-nucleoside reverse transcriptase inhibitors were detected in 88.3% of patients with virological failure of elsulfavirine-containing antiretroviral therapy. Previously described HIV-1 resistance profiles to elsulfavirine were detected in only 5.1% of the studied patients. A total of 29 mutations were detected, the most common being V106I (46.9%), E138K (38.5%), H221Y (34.6%), E138Q (20.7%), F227C (12.3%), Y181C (11.7%), K101E (11.2%), and E138A (10.6%). A total of 87 different HIV-1 mutation patterns were detected, with combinations of two or more mutations predominating (70.9%). The main patterns detected included combinations of mutations V106I/M, E138K/Q/G, and H221Y±K101E, F227C, G190S, and M230L. High levels of HIV-1 resistance in the studied patients were most frequently detected to rilpivirine (60.9%), which limits its successful use in patients taking elsulfavirine, and least frequently to doravirine (22.9%) and etravirine (9.5%), which allows them to be considered as options for switching. Conclusion . This study identified the main mutations associated with elsulfavirine-containing therapy failure, potential pathways for the development of HIV-1 resistance to the drug, and HIV-1 cross-drug resistance to other drugs in class. However, most of the patterns identified in this study have not been previously described, indicating the need to update data on the HIV1 resistance profile to elsulfavirine.
The study of the issue of impaired bone mineral density (BMD) in people living with human immunodeficiency virus (HIV) who were infected perinatally (from birth) has objective reasons for the development of osteoporosis (OP). However, information about the state of bone tissue in this group is limited and no studies have been conducted in Russia. The role of risk factors and approaches to diagnosis, treatment, and prevention of osteoporosis have not been determined. Objectives . To assess the state of BMD using densitometry in perinatal HIV-infected adults on antiretroviral therapy (ART). Material and methods . This study included patients with perinatal HIV infection (n = 38) (main group) who continue to be followed up in the adult department of a specialized center and patients with sexually acquired HIV infection (n = 36) (comparison group) who have reached adulthood but are not older than 25 years old. Both groups were not concurrently infected with HIV or HBV. Were analyzed the level of CD4+ lymphocytes and the HIV RNA. Hip and spine densitometry was performed to assess bone matrix status using the Z-score taking into account age group of study participants. Results . Patients with perinatal HIV infection had a disease duration similar to their age at the time of the study, while the duration of ART administration was 13 years with a maximum of 21 years and 5 months. BMI in the study group showed that 73.6% of indicators were within normal limits, 5 patients had low body weight and one had grade I obesity, accounting for 2.6% respectively. Currently, three (7.8%) patients had detectable levels of HIV RNA despite irregular ART intake, with no signifi cant diff erences in CD4 lymphocyte counts during analysis of this indicator. At the time of diagnosis, the proportion of patients with immunodefi ciency was 20.9%. However, at the time of the study, this proportion had increased to 23.2%. Hip and spine densitometry, two patients (5.2%) were identifi ed with signs of osteopenia. The cause of this disorder is multifactorial and includes the presence of HIV infection, duration of antiretroviral therapy, and, in one case, the presence of concurrent somatic pathology requiring constant intake of glucocorticosteroids. Conclusion . Patients with perinatal HIV infection are at risk of developing osteoporosis and require regular medical monitoring to detect bone mineral density (BMD) disorders early and treat them promptly.
The article is devoted to the topical problems of protecting the intellectual rights of companies that are manufacturers of medicines and drugs, taking into account the need to maintain a balance of interests of pharmaceutical companies, patients and the state, as well as the role of the patent system in this mechanism. Almost all medicines and medication created in different countries are initially registered today as objects of intellectual property and are protected by patents. In world practice, exclusive rights to the results of intellectual activity are among the most investment-attractive corporate assets. Therefore, the creativity of innovators who create new technical solutions should be properly stimulated for the purpose of subsequent organization of production in Russia for the production of new medical products on an industrial scale, including the latest medicines and medication. In addition, the regulatory framework should ensure the attraction of investments in the research activities of innovators and the subsequent commercialization of patented developments, in order to provide consumers with highly effective medicines at affordable prices. One of the ways to reduce the selling value of medical products demanded by the market is the use of legal mechanisms for compulsory licensing of patentable drugs, which is implemented in the civil legislation of Russia. It is generally accepted that these mechanisms can reduce the cost of medicines created on the basis of the latest developments. At the same time, the author draws attention to the complexity of the legal relationship arising between the copyright holder who owns the innovation and the licensee. If the patentee does not agree with the loss of the monopoly right to the created drug, he can overcome the legal monopoly on the patented product in court. The article considers such concepts as the conditions for issuing, features, positive and negative aspects of compulsory licensing, as well as an analysis of the established judicial practice in the field of granting a license and the possibility of subsequent development of the practice of concluding contracts of this type.
Lesions of the oral mucosa in people living with Human immunodeficiency virus (HIV) are characterized by a wide variety and high frequency of occurrence. According to some data, they are registered in half of HIV-positive individuals and in 80% of patients in the later stages of HIV infection. Publications on this topic report on more than twenty different types of diseases of the oral mucosa, most often diagnosed in HIV-infected individuals. Candidiasis is the earliest and most common secondary disease of HIV infection. While the spectrum of pathology has significant regional differences, candidiasis is the most common nosology on all continents. Diseases of the oral mucosa can be indicators of infection with the human immunodeficiency virus, early clinical symptoms of HIV infection, and also indicate its progression. The severity of lesions of the oral mucosa correlates with the level of immunosuppression: the lower the number of CD4+ T-lymphocytes, the more extensive the pathological process and the higher the relapse rate. Timely detection of diseases such as oral candidiases, hairy leukoplakia, Kaposi's sarcoma helps to establish the stage and phase of HIV infection in patients in accordance with the Russian clinical classification, and their regression or decrease in clinical manifestations indicates the effectiveness of antiretroviral therapy. The photo gallery presents various diseases of the oral mucosa in HIV-positive patients, including lesions often associated with HIV infection (hairy leukoplakia, Kaposi's sarcoma, non-Hodgkin's lymphoma, case series of various clinical variants of candidiasis). From the archive of author's. The photographs are published for the first time.
