The increasing use of the integrase strand transfer inhibitor (INSTI) class for the treatment of HIV-infection has pointed to the importance of analyzing the features of HIV-1 subtypes for an improved understanding of viral genetic variability in the occurrence of drug resistance (DR). In this study, we have described the prevalence of INSTI DR in a Russian cohort and the genetic features of HIV-1 integrase sub-subtype A6. We included 408 HIV infected patients who were not exposed to INSTI. Drug resistance mutations (DRMs) were detected among 1.3% of ART-naïve patients and among 2.7% of INSTI-naïve patients. The prevalence of 12 polymorphic mutations was significantly different between sub-subtypes A6 and A1. Analysis of the genetic barriers determined two positions in which subtype A (A1 and A6) showed a higher genetic barrier (G140C and V151I) compared with subtype B, and one position in which subtypes A1 and B displayed a higher genetic barrier (L74M and L74I) than sub-subtype A6. Additionally, we confirmed that the L74I mutation was selected at the early stage of the epidemic and subsequently spread as a founder effect in Russia. Our data have added to the overall understanding of the genetic features of sub-subtype A6 in the context of drug resistance.

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.

A molecular analysis of HIV-1 subtypes and recombinants circulating in cities in the Russian Far East was performed. The study included samples from 201 outpatients from Vladivostok, Khabarovsk, and Blagoveshchensk. In most parts of Russia, patients are infected with HIV-1 subtype A, known as the IDU-A variant. Subtype B, including the IDU-B variant, is rare in Russia but widespread in the Ukraine, and the CRF02_AG is prevalent in Central Asian countries and Siberia, Russia. One of the challenges of this study in the Far East was to determine whether the molecular landscape of HIV infection in this region is influenced by the bordering countries, including China and Japan, where a distinct set of HIV subtypes is circulating, such as B', C, and CRF01_AE. The distribution of HIV-1 genetic variants in the cities studied was as follows: subtype A (IDU-A), 55.7%; subtype B, 25.3% (IDU-B variant-24.3%); subtype C, 10.0%; CRF02_AG, 1.5%; and CRF63_02A1, 7.5%. A phylogenetic analysis confirmed the relationship of subtype A viruses with the IDU-A variant predominating in Ukraine, Russia and other former Soviet Union (FSU) countries, of subtype B viruses with IDU-B in the Ukraine and of CRF02_AG variants with variants in Uzbekistan, Russia, and other former USSR countries. Subtype C sequences were not uniform, and most clustered between each other and HIV-1 sequences originating from Africa; there was only one sample possibly related to Chinese variants. Thus, despite close cultural and commercial relationships among Russia, China, and Japan, the distribution of HIV-1 subtypes in the Russian Far East is still primarily influenced by contacts with the countries of the former USSR.

To analyze HIV-1 genetic variants in Kazakhstan, HIV-1 sequences were obtained from 205 antiretroviral-treated (ART) and naive patients in 2009-2013. Samples were collected in the most populous cities and provinces of Kazakhstan. On the basis of phylogenetic analyses of partial pol sequences, subtype A variant intravenous drug user (IDU)-A (which is dominant in the former Soviet Union) was found in 60.0% of the individuals, followed by CRF02_AG (34.6%); the rest of the samples were subtype B, CRF03_AB, CRF63_02A1, and CRF07_BC. The proportion of CRF02_AG has increased significantly since 2001-2003, when it was less than 5%. The majority of the CRF02_AG cases were found in Almaty, the former capital and the most populous city in Kazakhstan. The IDU-A variant dominated in the industrial regions of northern and central Kazakhstan and some other regions. Both dominant HIV-1 genetic variants were almost equally represented in the two main transmission groups: IDUs and heterosexuals. The analysis of drug-resistant mutations found a low prevalence of drug resistance in 165 therapy-naive individuals (3.0%). Thus, in the beginning of the second decade of the 2000s, the HIV epidemic in Kazakhstan is driven by two main genetic variants: IDU-A and CRF02_AG.

Objective: There is scarce information about the molecular epidemiology of HIV-infection in Armenia (former USSR). The objective of this work was to estimate the distribution of HIV-1 subtypes in this country and get any information about HIV drug resistance in naÏve patients. Design: A joint study involving 78 patients was carried out in Yerevan, Armenia and Moscow, Russia in 2009-2013. The cohort studies included mostly IDUs (28.2%) and heterosexuals (69.2%). Results: The phylogenetic analyses based on population sequencing of partial pol gene found subtype A1 being the most prevalent (92.3%), followed by subtype B (3.9%). The HIV-1 tropism inferred from env V3-loop sequences was determined in 27 samples, among them R5-tropic viruses were found in 13 (48.1%) patients and X4- variants – in 14 (51.9%) patients. The prevalence of drug resistance in naïve patients was low (1.5%) with the only one mutation K219Q found. Conclusion: The composition and distribution of HIV-1 genetic variants in Armenia are evidently influenced by the Russian and other FSU countries epidemic, due to the significant volume of Armenian migrant/re-emigrant flows. Continued surveillance of HIV-1 circulating subtypes and drug resistance in Armenia is important for the proper management of HIV infection in this country.