Studies of HIV-1 molecular epidemiology describe significant differences in HIV infection spread across geographical areas. We examined 80 HIV-1 samples from the Jewish Autonomous Region of Russia in 2024. HIV-1 genome sequences for 12 samples revealed a novel HIV-1 called CRF173_63A6. HIV-1 CRF173_63A6 was found to have arisen through recombination between a specific Russian A6 subtype and the recombinant virus CRF63_02A6, which is responsible for the PWID-associated HIV outbreak in the Siberian region of Russia. Phylogenetic analysis of pol sequences previously deposited in Genbank showed that the CRF173_63A6 samples we described are grouped into a common phylogenetic cluster that includes 54 HIV-1 samples isolated in the JAR and other areas of the Russian Far East, indicating a wide distribution of this virus genovariant. This study once again proves the significant contribution of the key PWID group not only to the development of local Russian HIV epidemics, but also to the change in the characteristics of the circulating virus population.

This study investigated the antiretroviral efficacy, toxicity profile, and cellular uptake of LNA-modified oligonucleotides within an in vitro HIV infection model. Phosphorothioate (PS) oligonucleotides, designed to bind conserved regions of the HIV-1 genome, were modified at the 3′ and/or 5′ ends with LNA nucleotides. The antiviral properties of oligonucleotides against HIV-1 subtype A6 were evaluated using human MT-4 cell cultures. The antiretroviral activity of LNA-oligonucleotides against HIV-1 has been established. Variations in the 50% inhibitory viral reproductive dose (IC50) values among the oligonucleotides were observed, depending upon both the target and the incorporated LNA modification. The optimal IC50 values (90 ± 10 nM) were achieved using a PS oligonucleotide lacking LNA modifications, which targeted the HIV-1 integrase-encoding genomic region. Optimal IC50 values (90 ± 10 nM) were achieved using a PS oligonucleotide lacking LNA modifications, which targeted the HIV-1 integrase-encoding genomic region. Optimal HIV inhibitory action among LNA constructs was observed in an oligonucleotide with a 5′-end LNA modification targeting the HIV integrase region (IC50 = 1.12 ± 0.03 μM). The introduction of LNA modifications to PS oligonucleotides failed to enhance antiviral activity, as demonstrated by IC50 values revealing significant in vitro HIV-1 inhibitory capacity. The internalization of oligonucleotides demonstrating optimal IC50 values was investigated via flow cytometry and imaging techniques. The PS modification has been demonstrated to exhibit the highest penetration efficiency. The characteristic features included low toxicity (maintaining >92% viable cells after 48 hours of culture), high cytoplasmic membrane sorption capacity (approximately 12% FAM+ cells after 48 hours), high penetration efficiency (approximately 98% FAM+ cells showing cytoplasmic signal), and elevated internalization and entropy ratios.