Transmission of high-level drug-resistance mutations in HIV-1 subtype A6 circulating among former Soviet Union countries

OBJECTIVES: For the past decade, the incidence of HIV has been on the rise in Eastern Europe and Central Asia, including the former Soviet Union (FSU) countries. Visa-free cross-border mobility in FSU nations has given rise to autochthonous transmission and emergence of region-specific pathogens. For this study, we analyzed drug resistance mutations (DRMs) in HIV-1 A6, the most prevalent subtype in the FSU region. METHODS: Using the Stanford database, we analyzed DRMs in 12,295 HIV-1 A6 pol sequences from 14 FSU countries. Using the Nextstrain pipeline, maximum-likelihood approach was used to perform phylogenetic and phylogeographic analyses. RESULTS: The most prevalent DRMs identified were nucleoside reverse transcriptase inhibitor (NRTI) DRMs A62V (39%) and M184V (18%); and non-NRTI (NNRTI) DRMs G190S (11%) and K103N (7%). Protease inhibitor DRMs were also detected at lower frequencies. Phylogenetic analyses revealed Russia, Ukraine, and Belarus to be significant hubs of A6 transmission, exhibiting overlapping clusters of sequences harboring NRTI and NNRTI DRMs, highlighting cross-border transmission of HIV variants harboring multiple-drug resistance. CONCLUSION: Our findings underscore the importance of regular surveillance of emerging DRMs across all major drug classes, including NRTIs, NNRTIs, and protease inhibitors, and tailored optimization of antiretroviral therapy regimens in the FSU region.