[Molecular epidemiological analysis of hiv infection in northern seaports of Russia].

The results of the molecular-epidemiological analysis of HIV-1 variants circulating in Arkhangelsk and Murmansk - northern seaports of Russia - were presented. In these seaports the HIV-1 variants belonging to subtype A1 were predominant (93% in Murmansk, 83% in Arkhangelsk). In addition to these variants, viruses of other subtypes such as B, C, D and recombinant forms CRF02_AG and CRF03_AB were identifed. The heterogeneity of circulating HIV-1 variants was higher in Arkhangelsk than in Murmansk. According to the results of phylogenetic analysis, subtype A1 sequences formed the common branch with nucleotide sequences of IDU-A strains found in other regions of Russia. HIV-1 variants of subtype B sub-clustered with sequences of East European B-variants. The recombinant strains CRF02_AG formed the common branch with HIV-1 sequences from Central Asia republics of the former USSR. Among 124 therapy-naive patients from Arkhangelsk and Murmansk (n = 124) the transmitted resistance was less than 5%.

[Molecular epidemiological analysis of HIV-1 variants circulating in Russia in 1987-2015]. / Molekuliarno-épidemiologicheskii analiz variantov VICh-1, tsirkulirovavshikh v Rossii v 1987-2015 gg.

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.

Analysis of the env gene variability of the IDU-A HIV-1 variant in the outbreak of the HIV infection epidemic in Perm region of Russia (1996-2011).

In the present work, a total of 132 HIV-1 env gene C2-V3-C3 sequences belonging to the IDU-A genetic variant were analyzed. The variants were obtained from the viruses circulating among IDUs and heterosexuals in the Perm region at different periods. It was shown that the rate of the divergence of the IDU-A HIV-1 viruses from a common ancestor increased 4.3 times (p < 0.001) in 2011 as compared with the onset of the epidemics. The rate of the HIV-1 evolution was different in the two risk groups of the infection. The mean genetic distance of HIV-1 variants circulating among heterosexuals was 1.3 times longer (p = 0.008) than that among IDUs. The accumulation rate of the nucleotide (including nonsynonymous) substitutions in the C2-V3-C3 HIV-1 env gene region among individuals infected by heterosexual contacts was 1.7 times higher than that among IDUs. The differences in the positions of the codons subjected to positive selection were demonstrated depending on the infection risk group tested.

[Molecular epidemiological analysis of HIV-1 in Kazakhstan in 2009-2013].

In this study pol gene analysis of 205 HIV-1 samples collected in Kazakhstan in 2009 and 2012-2013 was carried out. CRF02_AG variant is dominating in Almaty and actively circulates in East Kazakhstan Province. IDU-A variant is dominating in the rest of Kazakhstan. The data on low prevalence (3%) of HIV drug resistance mutations in native patients were obtained.

[Molecular epidemiological analysis of the HIV infection in the Blagoveshchensk and Khabarovsk Area (Russian Far East)].

The results of the molecular-epidemiological analysis of the HIV-1 variants circulating in Blagoveshchensk and Khabarovsk (Russian Far East) were presented. In Blagoveshchensk HIV-1 IDU-A variants were dominated (92.5%), similar to the regions of the European part of Russia. In Khabarovsk the heterogeneity of circulating HIV-1 variants was noted. In addition to IDU-A variants (66.0%), the strains of subtype B (12.6%), C (4.4%) and recombinant strain form CRF02_AG (17.0%) were identified. Using the phylogenetic analysis method the version of the penetration of HIV-1 variants from China and Japan was not supported.

Efficacy of first-line ART regimens based on tenofovir in HIV-infected patients with pre-existing A62V mutation in reverse transcriptase.

INTRODUCTION: The amino acid substitution A62V in reverse transcriptase was identified as a mutation correlated with virologic failure in patients on first-line therapy including tenofovir (TDF) and tenofovir alafenamide (TAF). A62V is a typically polymorphic mutation in HIV-1 sub-subtype A6, which is the most widespread virus variant in Russia. MATERIALS AND METHODS: The European EuResist (EIDB) database was queried to form two equivalent groups of patients: group 1 ‒ patients with A62V at baseline treated with TDF or TAF on the first-line therapy, group 2 ‒ patients without A62V at baseline treated with TDF or TAF on the first-line therapy. Each group included 23 patients. RESULTS: There was no statistical difference between the two groups in virologic efficacy in 4, 12, and 24 weeks after the start of antiretroviral therapy (ART) and in the frequency of virologic failures. CONCLUSION: This study has some limitations, and the exact role of A62V in the efficacy of the first-line ART based on tenofovir deserves further investigation.

[HIV-1 genetic variants in the Asian part of Russia: a study (2005-2010)].

The HIV-1 genetic variants circulated in the Asian part of the Russian Federation in 2005-2010 were studied. The samples of HIV-1 (427 in total) were collected in Khabarovsk, Magadan, Kurgan, Krasnoyarsk, Noyabr'sk, Yakutsk, Altay, and Tyva. Sequencing of some genome regions followed by the phylogenetic analysis or specific Internet resource sampling were used as the main methods of the HIV subtyping. The domination of the IDU-A HIV-1 genetic variant typical of HIV-infection epidemic in Russia was shown in all regions tested in 2005-2010. This variant prevailed both in IDUs and heterosexuals. In addition to IDU-A, some other HIV-1 genetic variants were found among them: subtype B and recombinant CRF03_AB. The HIV-1 genetic polymorphism in Russia was found to be low. An increase in the genetic distance among studied de novo samples was noted in the Asian part of Russia in 2005-2010 (26-68%) as compared to the European variants in 1996-1999 (10%).

[Genetic diversity of capsid protein (p24) in human immunodeficiency virus type-1 (HIV-1) variants circulating in the Russian Federation].

INTRODUCTION: The human immunodeficiency virus (HIV) protein p24 plays an important role in the life cycle of the virus, and also is a target for diagnostic tests and for new antiretroviral drugs and therapeutic vaccines. The most studied variant of HIV-1 in the world is subtype B. In Russia, the most common variant is A6, the spread of recombinant forms (CRF63_02A6, CRF03_A6B) is observed as well as circulation of G and CRF02_AG variants. However, a detailed study of the p24 protein in these variants has not yet been conducted. The aim was to study the features of the p24 protein in HIV-1 variants circulating in Russia and estimate the frequency of occurrence of pre-existing mutations associated with resistance to lenacapavir, the first antiretroviral drug in the class of capsid inhibitors. MATERIALS AND METHODS: The objects of the study were the nucleotide sequences obtained from the Los Alamos international database and clinical samples from HIV infected patients. RESULTS AND DISCUSSION: The features of HIV-1 variants circulating in Russia have been determined. V86A, H87Q, I91F are characteristic substitutions in A6 genome. It is shown that the presence of preexisting mutations associated with resistance to lenacapavir is unlikely. CONCLUSION: Features of the p24 protein in HIV-1 variants circulating in Russia allow them to be distinguished from others variants and among themselves. The prognosis for the use of lenacapavir in Russia is generally favorable. The results obtained could be taken into account in developing and using antiretroviral drugs and therapeutic vaccines.

[Analysis of the polymorphism of the genome region of HIV-1 encoding the fusion protein].

The prevalence of the mutations associated with HIV fusion inhibitor enfuvirtide resistance in Russia and CIS countries was studied. Enfuvirtide resistance mutations were not observed among studied viruses in Russia and CIS countries so far. It was found that high rate (35%) of natural polymorphism mutations were associated with enfuvirtide hypersusceptibility. It was also found that high frequency of accessory mutations N126K and E137K were observed in the HR2 region (27.5%). The accessory mutations in HR2 can contribute to increased resistance and improve viral fitness. Our data were compared with those obtained in similar previous studies.

[Molecular genetic characterization of the HIV-1 variants abundant in Kirgiziia].

The results of the molecular epidemiological analysis of HIV-1 circulating in Kirghizia were presented. In the area of Kirghizia this type of the work was performed for the first time. Two main genetic variants were discovered: variant IDU-A dominating in the area of the former Soviet Union, as well as recombinant form CRF02_AG. The possibility of further recombination process between these two variants of HIV-1 was suggested.

[Analysis of Tat protein characteristics in human immunodeficiency virus type 1 sub-subtype A6 (Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1)].

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.

[Analysis of the prevalence of CCR5 coreceptor antagonist resistance mutations among HIV-1 variants in Russia].

The authors studied the prevalence of mutations associated with resistance to the CCRS coreceptor antagonists maraviroc and vicriviroc in Russia. Most (93.6%) patients infected with HIV-1 genetic subtype A (IDU-A), predominant in the CIS countries, were found to have maraviroc resistance mutations. These mutations appear to reflect the natural genome polymorphism characteristic of the variant IDU-A. Maraviroc resistance mutations were of limited occurrence (2.8%) among the samples of virus subtype B in Russia. There were no vicriviroc resistance mutations in both the HIV-1 genetic variant IDU-A and the samples of virus subtype B. There is a need for further clinical studies evaluating the real impact of these mutations on the efficacy of maraviroc in patients infected with the HIV-1 genetic variant IDU-A.

[Molecular and epidemiology studies of HIV-1 prevalence in the Republic of Sakha (Yakutia)].

The gag, pol, and env genomic regions of HIV-1 variants currently circulating in the Republic of Sakha (Yakutia) were analyzed. The results of the study indicated that in this area there were HIV-1 variants belonging to two subtypes: A (IDU-A) and B, the former being predominant in this area and in the Russian Federation. The IDU-B-East strain was first isolated from a heterosexually infected patient, which suggests that the strain is outside the risk group of injection drug users. No cases of primary infection with resistant variants were notified during the study.

[Prediction of the efficacy of bevirimat used for the treatment of HIV infection in Russia].

The nucleotide sequences coding the CA-SP1 Pr55(gag) in 61 samples of HIV-1 subtype A variant IDU-A isolated in Russia were analyzed for bevirimat resistance mutations (CA-H226V, CA-L231F, CA-231M, SP1-A1V, SP1-A3T, SP1-A3V) and for polymorphisms in the GAG CA-SP1 cleavage site. None of the six bevirimat resistance mutations was found in the sequences analyzed. There were three polymorphisms CA-G225S, CA-R229K, CA-V2301 and a high variability in the C-terminus of SP1. The substitution SP-T8Q was observed in 98% of cases, which could probably affect the clinical efficacy of bevirimat. Therefore bevirimat can be potentially active in Russian patients infected with IDU-A variant, but strain-specific polymorphisms in combination with other virus genome mutations can influence the efficiency of bevirimat treatment.

[Drug resistance of HIV-1 as a result of using nevirapine for chemoprophylaxis of vertical viral transmission from HIV-infected mother to infant].

The review presents data on the use of a single prophylactic dose of nevirapine at labor given to a mother at the onset of labor in HIV-infected women and neonatal infants within 72 hours after birth in the absence of chemoprophylaxis with antiviral agents during pregnancy. The administration of nevirapine is shown to result in the occurrence of resistance mutations, most of which can be identified only if superfine methods are applied. Whether nevirapine may be used for chemoprophylaxis of the vertical transmission of the virus in Russia is discussed.

[Prediction of phenotype R5/X4 of HIV-1 variants circulating in Russia, by using computer methods].

The paper presents the data of a comparative analysis of various bioinformation methods for evaluating the tropism of HIV-1 subtype A that is typical of Russia. The prevalence of CXCR4- and CCR5-tropic viruses among the variants prevailing in Russia was studied using the B-PSSM (sinsi) prediction method. No X4-tropic variants were found among 124 samples of HIV-1 isolated from the Russian patients not receiving antiretrovirus therapy.

[Characterization of the structure of the 5'-LTR region of HIV-1 subtype A wide spread in Russia].

The nucleotide sequence of the 5'-LTR region of provirus DNA of 45 samples of the variant IDY-A of HIV-1 subtype A, which had been isolated from seropositive persons in Russia was analyzed. The structure of 5'-LTR was shown to have a high conservatism within the subtype A. The virus variants carrying the altered TAR peg structure gained no further acceptance. An insertion of 12 p.n. was detected in the MFNLP region, which was characteristic of Russian samples of subtype A and which had an additional binding site for factor RBF-2 that was able to affect viral replicative capacities. The Sp1 (II) and AP3-like sites, binding NF-AT factor, proved to be most variable.

[Comparative analysis of ViroSeq and Trugene HIV-1 genotyping systems in the application to the virus variants in Russia].

The ViroSeq (Celera Diagnostics) and Trugene (Bayer HealthCare) HIV-1 genotyping systems are widely used today in world clinical practice to detect drug resistance mutations resulting from ineffective treatment for HIV infection. Only the former test has gained acceptance. The present study has compared ViroSeq and Trugene genotyping systems used to identify both mutations of drug resistance and those of polymorphism in the HIV variants circulating in Russia where the unique strain IDU-A prevails. Analysis of 18 samples from HIV-infected patients who received and did not receive specific therapy has demonstrated that the agreement of the results of the tests was 95% (180 of the 190 mutations). At the same time, the results of resistance mutation detection by the ViroSeq and Trugene HIV-1 genotyping systems coincided completely. The fact that the Trugene HIV-1 genotyping system may be used along with the ViroSeq test system in clinical diagnostic laboratories is shown in the paper.

[Analysis of HIV-1 (Human immunodeficiency virus-1, Lentivirus, Orthoretrovirinae, Retroviridae) Nef protein polymorphism of variants circulating in the former USSR countries.]

INTRODUCTION: The human immunodeficiency virus (HIV) Nef protein is one of the key factors determining the infectivity and replicative properties of HIV. With the ability to interact with numerous proteins of the host cell, this protein provides the maximum level of virus production and protects it from the immune system. The main activities of Nef are associated with a decrease in the expression of the CD4 receptor and major histocompatibility complex class I molecules (MHC-I), as well as the rearrangement of the cytoskeleton. These properties of the protein are determined by the structure of several motifs in the structure of the nef gene encoding it, which is quite variable. OBJECTIVES: The main goal of the work was to analyze the characteristics of Nef protein of HIV-1 variant A6, which dominates in the countries of the former USSR. The objective of the work was a comparative analysis of natural polymorphisms in the nef gene of HIV-1 sub-subtypes A6 and A1 and subtype B. MATERIAL AND METHODS: The sequences of the HIV-1 genome obtained during the previous work of the laboratory were used, as well as the reference sequence from GenBank. In this work, Sanger sequencing and new generation sequencing methods, as well as bioinformation analysis methods were used. RESULTS AND DISCUSSION: The existence of noticeable differences in the prevalence of Nef natural polymorphisms (A32P, E38D, I43V, A54D, Q104K, H116N, Y120F, Y143F, V168M, H192T, V194R, R35Q, D108E, Y135F, E155K, E182M, R184K and F191L), some of which are characteristic mutations for variant A6, was shown. CONCLUSION: Characteristic substitutions were found in the Nef structure, potentially capable of weakening the replicative properties of HIV-1 variant A6.

[Molecular genetic characteristics of HIV-1 variants circulating in Cherepovets, Vologda region: the second case of the epidemic outbreak caused by the recombinant gagAenvB].

HIV-1 variants circulating in the town of Cherepovets, Vologda Region, were genetically analyzed. It was shown that that were predominantly two HIV-1 variants: IDU-A (19%) and the recombinant strain UDU-AIB (77%) that circulated in the region. Amongst the IDU-A strains, there were genotypes containing characteristic secondary drug resistance mutations in the pol gene of V771 and A62V, as well as variants of the wild type. Amongst IDU-AIB strains, only one variant of the virus had genotype V771. The recombinant form of HIV-1 was more common in injective drug users while a group of heterosexuals had both recombinant virus and the variant IDU-A, that is typical of other regions of Russia. Thus, the epidemic outbreak due to the recombinant HIV-1 strain IDU-AIB was first registered in Russia, outside the Kaliningrad Region.