Aim. To simultaneously analyze HIV-1 samples from all Russian regions to characterize the epidemiology of HIV infection in the country as a whole. Subjects and methods. The most extensive study was conducted to examine nucleotide sequences of the pol gene of HIV-1 samples isolated from HIV-positive persons in different regions of Russia, with the diagnosis date being fixed during 1987—2015. The nucleotide sequences of the HIV-1 genome were analyzed using computer programs and on-line applications to identify a virus subtype and new recombinant forms. Results. The nucleotide sequences of the pol gene were analyzed in 1697 HIV-1 samples and the findings were that the genetic variant subtype A1 (IDU-A) was dominant throughout the entire territory of Russia (in more than 80% of all infection cases). Other virus variants circulating in Russia were analyzed; the phenomenon of the higher distribution of the recombinant form CRF63/02A in Siberia, which had been previously described in the literature, was also confirmed. Four new recombinant forms generated by the virus subtype A1 (IDU-A) and B and two AG recombinant forms were found. There was a larger genetic distance between the viruses of IDU-A variant circulating among the injecting drug users and those infected through heterosexual contact, as well as a change in the viruses of subtype G that caused the outbreak in the south of the country over time in 1988—1989. Conclusion. The findings demonstrate continuous HIV-1 genetic variability and recombination over time in Russia, as well as increased genetic diversity with higher HIV infection rates in the population.

Background: Eastern Europe and Central Asia (EECA) is one of the regions where the HIV epidemic continues to grow at a concerning rate. Antiretroviral therapy (ART) coverage in EECA countries has significantly increased during the last decade, which can lead to an increase in the risk of emergence, transmission, and spread of HIV variants with drug resistance (DR) that cannot be controlled. Because HIV genotyping cannot be performed in these countries, data about HIV DR are limited or unavailable. Objectives: To monitor circulating HIV-1 genetic variants, assess the prevalence of HIV DR among patients starting antiretroviral therapy, and reveal potential transmission clusters among patients in six EECA countries: Armenia, Azerbaijan, Belarus, Russia, Tajikistan, and Uzbekistan. Materials and methods: We analyzed 1071 HIV-1 pol-gene fragment sequences (2253–3369 bp) from patients who were initiating or reinitiating first-line ART in six EECA counties, i.e., Armenia (n = 120), Azerbaijan (n = 96), Belarus (n = 158), Russia (n = 465), Tajikistan (n = 54), and Uzbekistan (n = 178), between 2017 and 2019. HIV Pretreatment DR (PDR) and drug resistance mutation (DRM) prevalence was estimated using the Stanford HIV Resistance Database. The PDR level was interpreted according to the WHO standard PDR survey protocols. HIV-1 subtypes were determined using the Stanford HIV Resistance Database and subsequently confirmed by phylogenetic analysis. Transmission clusters were determined using Cluster Picker. Results: Analyses of HIV subtypes showed that EECA, in general, has the same HIV genetic variants of sub-subtype A6, CRF63_02A1, and subtype B, with different frequencies and representation for each country. The prevalence of PDR to any drug class was 2.8% in Uzbekistan, 4.2% in Azerbaijan, 4.5% in Russia, 9.2% in Armenia, 13.9% in Belarus, and 16.7% in Tajikistan. PDR to protease inhibitors (PIs) was not detected in any country. PDR to nucleoside reverse-transcriptase inhibitors (NRTIs) was not detected among patients in Azerbaijan, and was relatively low in other countries, with the highest prevalence in Tajikistan (5.6%). The prevalence of PDR to nonnucleoside reverse-transcriptase inhibitors (NNRTIs) was the lowest in Uzbekistan (2.8%) and reached 11.1% and 11.4% in Tajikistan and Belarus, respectively. Genetic transmission network analyses identified 226/1071 (21.1%) linked individuals, forming 93 transmission clusters mainly containing two or three sequences. We found that the time since HIV diagnosis in clustered patients was significantly shorter than that in unclustered patients (1.26 years vs 2.74 years). Additionally, the K103N/S mutation was mainly observed in clustered sequences (6.2% vs 2.8%). Conclusions: Our study demonstrated different PDR prevalence rates and DR dynamics in six EECA countries, with worrying levels of PDR in Tajikistan and Belarus, where prevalence exceeded the 10% threshold recommended by the WHO for immediate public health action. Because DR testing for clinical purposes is not common in EECA, it is currently extremely important to conduct surveillance of HIV DR in EECA due to the increased ART coverage in this region.

Introduction. Tat protein is a major factor of HIV (human immunodeficiency virus) transcription regulation and has other activities. Tat is characterized by high variability, with some amino acid substitutions, including subtypespecific ones, being able to influence on its functionality. HIV type 1 (HIV-1) sub-subtype A6 is the most widespread in Russia. Previous studies of the polymorphisms in structural regions of the A6 variant have shown numerous characteristic features; however, Tat polymorphism in A6 has not been studied.Goals and tasks. The main goal of the work was to analyze the characteristics of Tat protein in HIV-1 A6 variant, that is, to identify substitutions characteristic for A6 and A1 variants, as well as to compare the frequency of mutations in functionally significant domains in sub-subtype A6 and subtype B.Material and methods. The nucleotide sequences of HIV-1 sub-subtypes A6, A1, A2, A3, A4, subtype B and the reference nucleotide sequence were obtained from the Los Alamos international database.Results and discussion. Q54H and Q60H were identified as characteristic substitutions. Essential differences in natural polymorphisms between sub-subtypes A6 and A1 have been demonstrated. In the CPP-region, there were detected mutations (R53K, Q54H, Q54P, R57G) which were more common in sub-subtype A6 than in subtype B.Conclusion. Tat protein of sub-subtype A6 have some characteristics that make it possible to reliably distinguish it from other HIV-1 variants. Mutations identified in the CPP region could potentially alter the activity of Tat. The data obtained could form the basis for the drugs and vaccines development.

In Russia, antiretroviral therapy (ART) coverage has significantly increased, which, in the absence of routine genotyping testing, could lead to an increase in HIV drug resistance (DR). The aim of this study was to investigate the patterns and temporal trends in HIV DR as well as the prevalence of genetic variants in treatment-naïve patients from 2006 to 2022, using data from the Russian database (4481 protease and reverse transcriptase and 844 integrase gene sequences). HIV genetic variants, and DR and DR mutations (DRMs) were determined using the Stanford Database. The analysis showed high viral diversity, with the predominance of A6 (78.4%), which was the most common in all transmission risk groups. The overall prevalence of surveillance DRMs (SDRMs) was 5.4%, and it reached 10.0% in 2022. Most patients harbored NNRTI SDRMs (3.3%). The prevalence of SDRMs was highest in the Ural (7.9%). Male gender and the CRF63_02A6 variant were association factors with SDRMs. The overall prevalence of DR was 12.7% and increased over time, primarily due to NNRTIs. Because baseline HIV genotyping is unavailable in Russia, it is necessary to conduct surveillance of HIV DR due to the increased ART coverage and DR prevalence. Centralized collection and unified analysis of all received genotypes in the national database can help in understanding the patterns and trends in DR to improve treatment protocols and increase the effectiveness of ART. Moreover, using the national database can help identify regions or transmission risk groups with a high prevalence of HIV DR for epidemiological measures to prevent the spread of HIV DR in the country.

Although HIV-1 subtype A has predominated in Russia since the end of the 20th century, other viral variants also circulate in this country. The dramatic outbreak of HIV-1 subtype G in 1988-1990 represents the origin of this variant spreading in Russia. However, full genome sequencing of the nosocomial viral variant and an analysis of the current circulating variants have not been conducted. We performed near full-length genome sequencing and phylogenetic and recombination analyses of 11 samples; the samples were determined to be subtype G based on an analysis of the pol region. Three samples were reliably obtained from patients infected during the nosocomial outbreak. The other 8 samples were obtained from patients who were diagnosed in 2010–2015. Phylogenetic analysis confirmed that a man from the Democratic Republic of the Congo was the origin of the outbreak. We also found that currently circulating viral variants that were genotyped as subtype G according to their pol region are in fact unique recombinant forms. These recombinant forms are similar to the BG-recombinants from Western Europe, particularly Spain and Portugal. The limitations of subtyping based on the pol region suggest that these viral variants are more widespread in Europe than is currently supposed.