Prevalence of HIV drug resistance at antiretroviral treatment failure across regions of Russia.

BACKGROUND: This study aimed to investigate mutations associated with, the causes of, and the conditions that contribute to HIV drug resistance (DR). This research provides crucial insights into the mechanisms through which HIV evades antiretroviral drugs and suggests strategies to counter this phenomenon. Our objective was to assess the prevalence and structure of DR in HIV-1 across various regions in Russia and identify the primary factors influencing the development of HIV DR. METHODS: The study used nucleotide sequences from the HIV-1 pol gene obtained from 1369 patients with a history of therapy and virological failure between 2005 and 2019 to analyze the frequency and structure of DR and the factors associated with it. RESULTS: The analysed HIV-1 genotypes included viruses resistant to nucleoside reverse transcriptase inhibitors (NRTIs; 11.8%), non-nucleoside reverse transcriptase inhibitors (NNRTIs; 6.4%), and NRTIs + NNRTIs (31.7%). The mutations M184V/I and G190A/S/E were the most prevalent, accounting for 54.5% and 26.6%, respectively. The dominance of multiple DR persisted throughout the entire observation period. The likelihood of encountering drug-resistant variants was increased among men, patients in the late stage of infection, and those with a viral load <30 000 RNA copies/mL. Injection drug use was not associated with DR. CONCLUSION: This study has yielded new insights into HIV DR in Russia, offering valuable information to identify clinical or programmatic events warranting closer attention and support.

Recombinant Forms of HIV-1 in the Last Decade of the Epidemic in the Russian Federation.

Currently, HIV-1 displays a substantial level of genetic diversity on a global scale, partly attributed to its recombinant variants. This study seeks to identify and analyze HIV-1 recombinants in Russia during the last decade of the epidemic. A comprehensive examination was conducted, encompassing 3178 partial pol sequences. Subtyping was achieved through various programs including COMET, the Stanford Database, REGA, jpHMM, RIP, and RDP4 for recombination analysis. The study also involved phylogenetic analysis to trace the origins of the identified recombinants. Primary resistance (PrimDR) prevalence and Drug Resistance Mutations (DRMs) were assessed. The study uncovered an overall proportion of recombinants at 8.7%, with a statistically significant increase in their frequency observed over time (p < 0.001). The Northwestern (18.5%) and Siberian (15.0%) Federal Districts exhibited a high prevalence of recombinants, while the Volga (1.9%) and Ural (2.8%) Federal Districts had a lower prevalence. Among HIV-1 recombinants, a PrimDR prevalence of 11.4% was identified. Notably, significant differences in DRMs were observed, with a higher prevalence of M184V in sub-subtype A6 (p = 0.018) and K103N in CRF63_02A6 (p = 0.002). These findings underscore the increasing HIV-1 genetic diversity and highlight a substantial prevalence of PrimDR among its recombinant forms, emphasizing the necessity for ongoing systematic monitoring.

Current Trends of HIV Infection in the Russian Federation.

Russia remains one of the areas most affected by HIV in Eastern Europe and Central Asia. The aim of this study was to analyze HIV infection indicators and study trends in Russia using data from the Federal Statistic Form No. 61 "Information about HIV infection". HIV incidence, prevalence, HIV testing and mortality rates (from 2011 to 2022), and treatment success rates (from 2016 to 2022) were analyzed. These indicators were compared across different federal districts (FDs) of Russia. The findings revealed a significant downward trend in HIV incidence, while a significant upward trend was observed for HIV prevalence. The mortality rate has stabilized since 2018. The coverage of HIV testing and antiretroviral therapy increased over time. The number of people living with HIV-1 (PLWH) with a suppressed viral load in Russia as a whole varied between 72% and 77% during the years under observation. The Siberian and Ural federal districts recorded the highest HIV incidence, while the North Caucasian FD reported the lowest. An increase in HIV testing coverage was observed across all FDs. This comprehensive evaluation of HIV infection indicators within the regional context contributes to the timely implementation of measures aimed at preventing the spread of HIV.

Features of Tat Protein in HIV-1 Sub-Subtype A6 Variants Circulating in the Moscow Region, Russia.

Tat, the trans-activator of transcription, is a multifunctional HIV-1 protein that can induce chronic inflammation and the development of somatic diseases in HIV-infected patients. Natural polymorphisms in Tat can impact the propagation of the inflammatory signal. Currently, Tat is considered an object for creating new therapeutic agents. Therefore, the identification of Tat protein features in various HIV-1 variants is a relevant task. The purpose of the study was to characterize the genetic variations of Tat-A6 in virus variants circulating in the Moscow Region. The authors analyzed 252 clinical samples from people living with HIV (PLWH) with different stages of HIV infection. Nested PCR for two fragments (tat1, tat2) with subsequent sequencing, subtyping, and statistical analysis was conducted. The authors received 252 sequences for tat1 and 189 for tat2. HIV-1 sub-subtype A6 was identified in 250 samples. The received results indicated the features of Tat1-A6 in variants of viruses circulating in the Moscow Region. In PLWH with different stages of HIV infection, C31S in Tat1-A6 was detected with different occurrence rates. It was demonstrated that Tat2-A6, instead of a functional significant 78RGD80 motif, had a 78QRD80 motif. Herewith, G79R in Tat2-A6 was defined as characteristic amino acid substitution for sub-subtype A6. Tat2-A6 in variants of viruses circulating in the Moscow Region demonstrated high conservatism.

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.

Reconstructing the Temporal Origin and the Transmission Dynamics of the HIV Subtype B Epidemic in St. Petersburg, Russia.

The HIV/AIDS epidemic in Russia is among the fastest growing in the world. HIV epidemic burden is non-uniform in different Russian regions and diverse key populations. An explosive epidemic has been documented among people who inject drugs (PWID) starting from the mid-1990s, whereas presently, the majority of new infections are linked to sexual transmission. Nationwide, HIV sub-subtype A6 (previously called AFSU) predominates, with the increasing presence of other subtypes, namely subtype B and CRF063_02A. This study explores HIV subtype B sequences from St. Petersburg, collected from 2006 to 2020, in order to phylogenetically investigate and characterize transmission clusters, focusing on their evolutionary dynamics and potential for further growth, along with a socio-demographic analysis of the available metadata. In total, 54% (107/198) of analyzed subtype B sequences were found grouped in 17 clusters, with four transmission clusters with the number of sequences above 10. Using Bayesian MCMC inference, tMRCA of HIV-1 subtype B was estimated to be around 1986 (95% HPD 1984-1991), whereas the estimated temporal origin for the four large clusters was found to be more recent, between 2001 and 2005. The results of our study imply a complex pattern of the epidemic spread of HIV subtype B in St. Petersburg, Russia, still in the exponential growth phase, and in connection to the men who have sex with men (MSM) transmission, providing a useful insight needed for the design of public health priorities and interventions.

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.

Identifying HIV-1 Transmission Clusters in Uzbekistan through Analysis of Molecular Surveillance Data.

The CRF02_AG and sub-subtype A6 are currently the predominant HIV-1 variants in the Republic of Uzbekistan, but little is known about their time-spatial clustering patterns in high-risk populations. We have applied molecular evolution methods and network analyses to better understand the transmission patterns of these subtypes by analyzing 316 pol sequences obtained during the surveillance study of HIV drug resistance. Network analysis showed that about one third of the HIV infected persons were organized into clusters, including large clusters with more than 35 members. These clusters were composed mostly of injecting drug users and/or heterosexuals, with women having mainly high centrality within networks identified in both subtypes. Phylogenetic analyses of the 'Uzbek' sequences, including those publicly available, show that Russia and Ukraine played a role as the main sources of the current subtype A6 epidemic in the Republic. At the same time, Uzbekistan has been a local center of the CRF02_AG epidemic spread in the former USSR since the early 2000s. Both of these HIV-1 variants continue to spread in Uzbekistan, highlighting the importance of identifying transmission networks and transmission clusters to prevent further HIV spread, and the need for HIV prevention and education campaigns in high-risk groups.

Correction: Prevalence and spatiotemporal dynamics of HIV-1 Circulating Recombinant Form 03_AB (CRF03_AB) in the Former Soviet Union countries.

[This corrects the article DOI: 10.1371/journal.pone.0241269.].

Prevalence and spatiotemporal dynamics of HIV-1 Circulating Recombinant Form 03_AB (CRF03_AB) in the Former Soviet Union countries.

BACKGROUND: HIV-1 circulating recombinant forms (CRFs) infections has been increasing in Former Soviet Union (FSU) countries in the recent decade. One is the CRF03_AB, which circulated in the region since late 1990s and probably became widespread in northwestern FSU countries. However, there is not much information provided about the dissemination of this recombinant. Here, we examine the prevalence, evolutionary dynamics and dispersion pattern of HIV-1 CRF03_AB recombinant. METHODS: We analyzed 32 independent studies and 151 HIV-1 CRF03_AB pol sequences isolated from different FSU countries over a period of 22 years. Pooled prevalence was estimated using a random effects model. Bayesian coalescent-based method was used to estimate the evolutionary, phylogeographic and demographic parameters. RESULTS: Our meta-analysis showed that the pooled prevalence of CRF03_AB infection in northwestern FSU region was 5.9% [95%CI: 4.1-7.8]. Lithuania (11.6%), Russia (5.9%) and Belarus (2.9%) were the most affected by CRF03_AB. We found that early region wide spread of HIV-1 CRF03_AB originated from one viral clade that arose in the city of Kaliningrad in 1992 [95%HPD: 1990-1995]. Fourteen migration route of this variant were found. The city of Kaliningrad is involved in most of these, confirming its leading role in CRF03_AB spread within FSU. Demographic reconstruction point to this is that CRF03_AB clade seems to have experienced an exponential growth until the mid-2000s and a decrease in recent years. CONCLUSION: These data provide new insights into the molecular epidemiology of CRF03_AB as well as contributing to the fundamental understanding of HIV epidemic in FSU.