Acquired drug resistance of HIV in patients with virological failure of first-line art

Aim of the study: to assess quantitative and qualitative indicators of HIV drug resistance to antiretroviral drugs in patients with virological failure of first-line ART.

Materials and methods. Clinical and laboratory parameters and results of HIV molecular genetic testing were analyzed in 964 patients with virological failure of antiretroviral therapy (ART) in 2018–2022 at the St. Petersburg AIDS Center.

Fragments of the pol gene encoding HIV enzymes were examined by PCR and Sanger sequencing. Identification of HIV drug resistance mutations to antiretroviral therapy was performed using the Stanford University HIVDB algorithm Version 9.4.1. The dynamics of HIV resistance prevalence among ART recipients were assessed by comparing the results of two studies: a retrospective study (2006–2011) and a current study (2018–2022) in St. Petersburg.

Results and discussion. Virological failure was associated with the development of HIV resistance mutations in 76.5% of patients. HIV resistance mutations were found in the majority of cases (93.9%) in patients receiving first-line ART. Regimens consisting of 2 nucleoside reverse transcriptase inhibitors (NRTI) + non-nucleoside reverse transcriptase inhibitors (NNRTI) combination were more frequently used (72.1%), the proportion of first-generation NNRTI class drugs was 58,7%.

According to the results of HIV resistance testing, resistance to the NRTI (90.6%) and NNRTI (78.3%) classes was more common than to protease inhibitors (PI) (3.8%) and integrase strand transfer inhibitors (INSTI) (0.9%). HIV resistance to two drug classes was found in 74,2% of patients, most frequently to the NRTI+NNRTI classes (71.3%). Multidrug resistance to three drug classes (NRTI+NNRTI+PI) was rarely detected, only in 1.3% of patients.

Analysis of HIV resistance to antiretroviral drugs in patients over time showed an increase in resistance to NRTIs (from 79.8% to 90.6%) and NNRTIs (from 60.4% to 78.3%), comparing the periods 2006–2011 and 2018–2022. There was also a decrease in the number of patients with resistance to PIs (from 19.9% to 3.8%).

Conclusion. Our study shows that acquired HIV drug resistance was the leading cause of virological ineffectiveness of antiretroviral therapy between 2018 and 2022. Importantly, the majority of HIV drug resistance was observed in patients receiving first-line therapy.

These findings highlight the need to modernize first-line ART regimens, including the wider introduction into clinical practice of drugs with a high genetic barrier to resistance. These include modern integrase inhibitors or protease inhibitors. The choice of ART regimen should be based on the patient’s previous drug history and HIV resistance indicators. When selecting a new regimen plan for patients with multidrug-resistant HIV, it is essential to use at least two or three medications (typically from different classes) that do not have any resistance mutations.

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