HIV Drug Resistance in the Era of Modern Antiretroviral Therapy (Review)

The widespread use of antiretroviral therapy (ART), including in low- and middle-income countries, on the one hand, has reduced HIV-related morbidity and mortality, but on the other hand, it has led to an increase in the number of cases of HIV infection associated with a variant of the virus resistant to ART drugs. Although cases of drug resistance to modern ART regimens are rare, an analysis of foreign literature in recent years has shown that the problem of HIV drug resistance is relevant, especially for low- and middle-income countries, given the fact that the latter widely use ART regimens based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) of HIV, to which the level of resistance is higher compared to more modern ART regimens. Objective — to highlight the importance of prevention and control of HIV drug resistance as one of the reasons for limiting the possibilities of ART and reducing its effectiveness. Materials and methods. A search for sources of information on HIV drug resistance was conducted in the scientometric databases Scopus, Web of Science, Google Scholar, PubMed using the following keywords: «HIV resistance», «HIV resistance testing», «HIV drug resistance mutations». After processing the publications, professional sources that met the query conditions were selected for review. Preference was given to sources of information that were published from 2020 to 2024. Results and discussion. The basis of changes in the genetic structure of HIV is multiple drug resistance mutations (MDRs), which can appear both during the suppression of viral replication by ART drugs (mutations that arise during treatment) and be transmitted during primary HIV infection (mutations that are transmitted). The latter are associated with virological failure and limitation of ART options in patients even before the start of treatment. Analysis of literature sources showed that the prevalence of drug resistance varies between countries, but in general does not exceed 20 % for most countries and is mostly found with the use of earlier ART regimens. Based on this, it is extremely important to take into account the full history of ART and the results of current and previous resistance tests. However, it should be taken into account that testing for HIV drug resistance is not a routine method of research in low- and middle-income countries.Modern ART regimens have higher barriers to the development of drug resistance. The selection of ART drugs with a high resistance barrier and the control of drug resistance mutations are key to success in preventing the development of the latter.The most common way to test for HIV resistance to ART drugs is the use of genotypic tests. Among the latter, next-generation sequencing (NGS) is a promising method for detecting drug resistance mutations, which is urgently needed in improving HIV diagnostics and surveillance, especially in identifying patients at risk of virological failure during first-line ART based on NNRTIs of HIV. Conclusions. HIV drug resistance is not common and is mostly found in low- and middle-income countries that use ART regimens with lower resistance barriers, such as NNRTIs. Therefore, the choice of modern ART regimens with high resistance thresholds is a key step in preventing the development of HIV drug resistance. Genotypic tests, such as NGS, are the preferred methods for testing of HIV resistance. In turn, the prevention and control of HIV drug resistance is crucial to maintaining the effectiveness of modern antiretroviral drugs.