HIV-1 Drug Resistance among Treatment-Naïve Patients in Russia: Analysis of the National Database, 2006-2022.

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.

Identification of Molecular Mechanisms Involved in Viral Infection Progression Based on Text Mining: Case Study for HIV Infection.

Viruses cause various infections that may affect human lifestyle for durations ranging from several days to for many years. Although preventative and therapeutic remedies are available for many viruses, they may still have a profound impact on human life. The human immunodeficiency virus type 1 is the most common cause of HIV infection, which represents one of the most dangerous and complex diseases since it affects the immune system and causes its disruption, leading to secondary complications and negatively influencing health-related quality of life. While highly active antiretroviral therapy may decrease the viral load and the velocity of HIV infection progression, some individual peculiarities may affect viral load control or the progression of T-cell malfunction induced by HIV. Our study is aimed at the text-based identification of molecular mechanisms that may be involved in viral infection progression, using HIV as a case study. Specifically, we identified human proteins and genes which commonly occurred, overexpressed or underexpressed, in the collections of publications relevant to (i) HIV infection progression and (ii) acute and chronic stages of HIV infection. Then, we considered biological processes that are controlled by the identified protein and genes. We verified the impact of the identified molecules in the associated clinical study.

Molecular Epidemiology of HIV-1 in Eastern Europe and Russia.

The HIV epidemic in Eastern Europe and Russia is large and not well-controlled. To describe the more recent molecular epidemiology of HIV-1, transmitted drug resistance, and the relationship between the epidemics in this region, we sequenced the protease and reverse transcriptase genes of HIV-1 from 812 people living with HIV from Ukraine (n = 191), Georgia (n = 201), and Russia (n = 420) before the initiation of antiretroviral therapy. In 190 Ukrainian patients, the integrase gene sequence was also determined. The most reported route of transmission was heterosexual contact, followed by intravenous drug use, and men having sex with men (MSM). Several pre-existing drug resistance mutations were found against non-nucleoside reverse transcriptase inhibitors (RTIs) (n = 103), protease inhibitors (n = 11), and nucleoside analogue RTIs (n = 12), mostly polymorphic mutations or revertants. In the integrase gene, four strains with accessory integrase strand transfer inhibitor mutations were identified. Sub-subtype A6 caused most of the infections (713/812; 87.8%) in all three countries, including in MSM. In contrast to earlier studies, no clear clusters related to the route of transmission were identified, indicating that, within the region, the exchange of viruses among the different risk groups may occur more often than earlier reported.

HIV-1 Sub-Subtype A6: Settings for Normalised Identification and Molecular Epidemiology in the Southern Federal District, Russia.

Russia has one of the largest and fastest growing HIV epidemics. However, epidemiological data are scarce. Sub-subtype A6 is most prevalent in Russia but its identification is challenging. We analysed protease/reverse transcriptase-, integrase-sequences, and epidemiological data from 303 patients to develop a methodology for the systematisation of A6 identification and to describe the HIV epidemiology in the Russian Southern Federal District. Drug consumption (32.0%) and heterosexual contact (27.1%) were the major reported transmission risks. This study successfully established the settings for systematic identification of A6 samples. Low frequency of subtype B (3.3%) and large prevalence of sub-subtype A6 (69.6%) and subtype G (23.4%) were detected. Transmitted PI- (8.8%) and NRTI-resistance (6.4%) were detected in therapy-naive patients. In therapy-experienced patients, 17.3% of the isolates showed resistance to PIs, 50.0% to NRTI, 39.2% to NNRTIs, and 9.5% to INSTIs. Multiresistance was identified in 52 isolates, 40 corresponding to two-class resistance and seven to three-class resistance. Two resistance-associated-mutations significantly associated to sub-subtype A6 samples: A62VRT and G190SRT. This study establishes the conditions for a systematic annotation of sub-subtype A6 to normalise epidemiological studies. Accurate knowledge on South Russian epidemiology will allow for the development of efficient regional frameworks for HIV-1 infection management.

Molecular Epidemiology of HIV-1 Subtype G in the Russian Federation.

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.

Genetic Variants of HIV Type 1 in Men Who Have Sex with Men in Russia.

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, AFSU (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 BFSU, 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.

HIV Infection: Progress and Problems.

Today, the most adequate and complete explanation of the main phenomena of clinico-immunological disease picture was suggested by D. Ho and his team (1998). According to their model, HIV infection is not slow infection, but acute productive process, lasting for many years with development AIDS. First of all, in this process specific cytotoxic lymphocytes and antibody-dependent cell cytotoxicity play an active role, as well as apoptotic processes, hyperproduction of pro-inflammatory cytokines, development of autoimmune disorders, direct cytotoxic action of envelope viral proteins The investigations, carried out in Scientific Educational and Industrial Complex "Clinical Immunology" of Rostov-Don State Medical University, have shown that the changes of macrophage functional activity during HIV infection are in dependence upon many factors, especially patient's age. The progression of HIV infection is accompanied with increase of CD95 expression on all lymphocytes, but especially on CD4(+) subpopulation at the stage of AIDS-associated infections. In this group of lymphocytes there is the highest number of cells with DNA degradation that is characteristic of terminal phase of apoptosis. It is possible to make a conclusion that both the viral factors, and the functional features of patient's immune system have great importance for pathogenesis of one or another variant of HIV infection course.