Frequency of Major Transmitted Integrase Resistance in Poland Remains Low Despite Change in Subtype Variability

Area of Science:

• Virology
• Epidemiology
• Public Health

Background:

• Integrase inhibitors are crucial for HIV treatment and prevention.
• Long-acting cabotegravir use is expanding in pre-exposure prophylaxis and treatment.
• Molecular surveillance of transmitted integrase resistance is increasingly important.

Purpose of the Study:

• To determine the frequency of transmitted integrase inhibitor resistance mutations (DRMs) in treatment-naïve individuals in Poland.
• To analyze trends in integrase resistance from 2016 to 2023.
• To assess the impact of HIV subtype variability on resistance patterns.

Main Methods:

• Sanger sequencing was used to analyze INSTI resistance in 882 treatment-naïve individuals.
• Integrase DRMs were identified using Stanford HIV drug resistance database scores.
• Phylogenetic analysis and logistic regression were employed for subtyping, clustering, and trend analysis.

Main Results:

• Major integrase mutations (E138K, R263K) were found in 0.45% of cases.
• Minor mutations, primarily E157Q (13.95%), were observed in 14.85% of individuals.
• No major clusters of transmitted drug resistance were identified, and E157Q transmission showed a decreasing trend (p < 0.001).
• An increase in sub-subtype A6 was noted, mainly among migrants and associated with L74 mutations.

Conclusions:

• The frequency of major transmitted integrase DRMs in Poland remains low.
• Despite shifts in HIV subtype variability, vigilance in molecular surveillance is essential.
• Continuous monitoring is vital for the effective use of integrase inhibitors, particularly with the rollout of long-acting cabotegravir.