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Background: Natural variability of integrase (IN) across HIV-1 variants may influence the emergence of resistant viruses. The most apparent explanation of this fact is the IN polymorphism and the associated differences in codon usage, which in turn, influence the probability and the terms of DRMs acquisition. Possible mechanisms by which polymorphisms affect DRMs emergence remain disputed and should still be clarified because these substitutions may be associated with a reduced activity of some INSTIs and may impact on ART regimen choice depending of HIV-1 subtype., Objective: The aim of this work was to assess the prevalence of naturally occurring polymorphisms within the HIV-1 integrase gene, which might influence the susceptibility to INSTIs, among the patients from Russia and former USSR countries, according to HIV-1 subtypes., Method: A study involved 506 HIV-1 IN sequences of INSTI-naive patients from Russia, Ukraine, Armenia, Kyrgyzstan, Kazakhstan, Uzbekistan, Belarus, and Georgia. Among them, 194 sequences were newly obtained in this study and 312 were downloaded from Los-Alamos database. The proviral DNA was sequenced using an in-house PCR protocol designed on the basis of a well-conserved integrase region in order to detect all HIV-1 variants., Results: The phylogenetic analyses based on IN population sequencing found subtype A6 being the most prevalent (259) (51.2%) in the collection studied, followed by subtype G (36) (7.1%), AGrecombinants (148) (29.3%), subtype B (50) (9.9%), and CRF03_AB (5) (1.0%). The major INSTI resistance-associated mutations (DRMs) were found only in two A6 samples. The prevalence of minor/ accessory substitutions depended on HIV-1 variants, while the most notable findings were L74I in subtype A6 (93.1%) and E157Q in subtype B (44.0%). Most of minor DRMs and polymorphic substitutions were concentrated in the central catalytic domain of the IN molecule. Both the DDE triad and HHCC zinc binding motifs were fully conserved., Conclusion: The results of the study suggest a very low risk of initiating INSTI-based therapy in patients with pre-existing polymorphic mutations in Russia and FSU countries. The therapy response in dominating HIV-1 genetic variants might be further studied in the future for a better understanding of their effect on INSTI susceptibility. The INSTI TDR is absent for the moment, but the risk may increase with expanded use of INSTIs, indicating the need for ongoing surveillance., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The men who have sex with men (MSM) population infected with HIV is poorly studied in Russia because of stigma and discrimination. In the first years of the HIV epidemic, the only HIV genetic variant that circulated among MSM was subtype B, usually acquired abroad. Meanwhile, the massive epidemic of HIV in Russia was caused by a highly homogenic subtype A variant, A FSU (A6), and spread mainly among drug users. In this study, 155 HIV pol sequences from MSM collected during the 2006-2016 period were analyzed. Phylogenetic analysis found that 19.4% of the viral sequences from MSM clustered with HIV genetic variants A6 and B FSU , which were previously identified only among drug users and their heterosexual partners. These data show that the MSM population in Russia is gradually becoming less isolated from the general epidemic process. Urgent measures should be taken to prevent the spread of HIV among the MSM population.

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.

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.