HIV drug resistance: molecular mechanisms, clinical significance, and current approaches to adjusting antiretroviral therapy (literature review)

Abstract

Introduction. Drug resistance of the human immunodeficiency virus (HIV) remains one of the key challenges in modern infectious diseases, significantly affecting the effectiveness of antiretroviral therapy and long-term disease prognosis. The high genetic variability of HIV contributes to the rapid emergence of resistance mutations and complicates the selection of effective treatment regimens. Objective. To analyze current data on the molecular mechanisms of HIV drug resistance, evaluate their clinical significance, and review modern approaches to the diagnosis and optimization of antiretroviral therapy. Materials and methods. A review of Russian and international scientific publications on HIV drug resistance mechanisms published in recent years was performed using specialized medical databases. The analysis included data from clinical and experimental studies, systematic reviews, and clinical guidelines focusing on resistance mutations, diagnostics, and treatment of HIV infection. Results and discussion. Drug resistance development is associated with the accumulation of mutations in genes encoding reverse transcriptase, protease, and integrase, as well as with the impact of viral genetic variability and subtype diversity. Cross-resistance and compensatory mutations play an important role in maintaining viral replicative capacity. Modern diagnostic methods, including genotypic and phenotypic testing as well as next-generation sequencing technologies, allow detection of minor viral variants and improve the prediction of treatment efficacy. Clinical evidence indicates that both transmitted and acquired resistance significantly influence the risk of virological failure and the choice of treatment regimens. Conclusion. Genetic variability of HIV and the emergence of resistance mutations are key factors determining the effectiveness of antiretroviral therapy. The use of advanced diagnostic methods and personalized treatment approaches can improve therapeutic outcomes and reduce the spread of drug-resistant HIV strains.