Kemerovo Oblast (KO) has had the highest rate of HIV spread in Russia since 2011. The aim of this work was to study the genetic variation of HIV-1 in Kemerovo Oblast. Blood was sampled from a total of 91 HIV-positive antiretroviral-therapy-naïve individuals in 2013 (38) and 2015 (53). HIV-1 subtypes, pol gene drug resistance mutations, and viral tropism were analyzed. In 2013-2015, the prevalence of HIV-1 subtype A decreased in KO from 60.5 to 7.5 %. The samples collected in 2015 from the patients with newly diagnosed HIV demonstrate the current dominance of HIV-1 CRF63_02A1 (71.7 %) and HIV-1 URF63_A1 (20.8 %), their parental viruses being CRF63_02A1 and subtype A. The initially predominant genetic variant, HIV-1 subtype A, was replaced in KO. An unusually high incidence of HIV-1 unique recombinant forms is probably the result of HIV-1 CRF63_02A1 introduction in the group of injection drug users with the initial HIV-1 subtype A infection and the practice of risky behavior that promotes reinfection. HIV-1 CRF63_02A1, which recently emerged in Siberia, and its recombinant forms have an ever-increasing impact on the current HIV epidemic in Russia, making urgent the need for in-depth study of this HIV-1 genetic variant.
Kyrgyzstan has one of the highest rates of HIV-1 spread in Central Asia. In this study, we used molecular–epidemiological approaches to examine the HIV-1 epidemic in Kyrgyzstan. Samples were obtained from HIV-positive individuals who visited HIV/AIDS clinics. Partial pol gene sequences were used to identify HIV-1 subtypes and drug resistance mutations (DRMs) and to perform phylogenetic analysis. Genetic diversity and history reconstruction of the major HIV-1 subtypes were explored using BEAST. This study includes an analysis of 555 HIV-positive individuals. The study population was equally represented by men and women aged 1–72 years. Heterosexual transmission was the most frequent, followed by nosocomial infection. Men were more likely to acquire HIV-1 during injection drug use and while getting clinical services, while women were more likely to be infected through sexual contacts (p < 0.01). Heterosexual transmission was the more prevalent among individuals 25–49 years old; individuals over 49 years old were more likely to be persons who inject drugs (PWID). The major HIV-1 variants were CRF02_AG, CRF63_02A, and sub-subtype A6. Major DRMs were detected in 26.9% of the study individuals; 62.2% of those had DRMs to at least two antiretroviral (ARV) drug classes. Phylogenetic analysis revealed a well-defined structure of CRF02_AG, indicating locally evolving sub-epidemics. The lack of well-defined phylogenetic structure was observed for sub-subtype A6. The estimated origin date of CRF02_AG was January 1997; CRF63_02A, April 2004; and A6, June 1995. A rapid evolutionary dynamic of CRF02_AG and A6 among Kyrgyz population since the mid-1990s was observed. We observed the high levels of HIV-1 genetic diversity and drug resistance in the study population. Complex patterns of HIV-1 phylogenetics in Kyrgyzstan were found. This study highlights the importance of molecular–epidemiological analysis for HIV-1 surveillance and treatment implementation to reduce new HIV-1 infections.
Purpose of the study. To study the characteristics of acute HIV infection in adults in the Novosibirsk region in 2017– 2018.Materials and methods. 200 patients with acute HIV infection, residents of the Novosibirsk region, aged 15 to 74 years, hospitalized in 2017–2018, 104 men and 96 women were examined. The diagnosis was verified by detecting antibodies to HIV in ELISA with a negative or doubtful result of the immunoblot, as well as by determining the quantitative content of HIV RNA in the blood by PCR. The hemogram, the content of CD4 + lymphocytes in the blood were determined. In addition, HIV-1 was studied in 71 patients for belonging to a genetic group.Results. Patients of 20–40 years old prevailed – 70.5%. The sexual way was dominant in women (69.0%), injecting psychoactive substances was more often in men (32.2%). Frequent symptoms were fever (99%), exanthema (65.5%), polylimfoadenopathy (54.0%). Less common were diarrhea (36.0%), pharyngotonsillitis (23.0%), aphthous stomatitis (6.5%), hepatomegaly or hepatosplenomegaly (8.5%). Secondary diseases were revealed in 26.5% of patients. Leukopenia was recorded in 63.0%, thrombocytopenia in 62.5%, lymphocytosis and atypical cells of the lymphoid series in 14.0%. All patients had a high “viral load” – from 23,000 to 10,000,000 or more copies / ml, a decrease in the number of CD4 + less than 350 cells – in 38.0%. From among 71 patients, 19.7% had HIV-1 subtype A, and 76.0% had recombinant HIV-1 CRF63_02A. In the latter, “viral load” of more than 10,000,000 copies / ml was more often recorded (67.8% vs. 33.4%, p = 0.004).Conclusion. A significant number of cases of acute HIV infection were reported in the Novosibirsk region in 2017– 2018. Its detection is possible by examination of all febrile patients who apply to medical institutions. Early initiation of antiretroviral therapy with the appointment of well-tolerated regimens contributes to the formation of a high commitment to therapy.
The high genetic variability of the human immunodeficiency virus (HIV-1) leads to a constant emergence of new genetic variants, including the recombinant virus CRF63_02A1, which is widespread in the Siberian Federal District of Russia. We studied HIV-1 CRF63_02A1 integrase (IN_CRF) catalyzing the incorporation of viral DNA into the genome of an infected cell. The consensus sequence was designed, recombinant integrase was obtained, and its DNA-binding and catalytic activities were characterized. The stability of the IN_CRF complex with the DNA substrate did not differ from the complex stability for subtype A and B integrases; however, the rate of complex formation was significantly higher. The rates and efficiencies of 3-processing and strand transfer reactions catalyzed by IN_CRF were found to be higher, too. Apparently, all these distinctive features of IN_CRF may result from specific amino acid substitutions in its N-terminal domain, which plays an important role in enzyme multimerization and binding to the DNA substrate. It was also found that the drug resistance mutations Q148K/G140S and G118R/E138K significantly reduce the catalytic activity of IN_CRF and its sensitivity to the strand transfer inhibitor raltegravir. Reduction in sensitivity to raltegravir was found to be much stronger in the case of double-mutation Q148K/G140S.
HIV-1 epidemic in Russia is one of the fastest growing in the world reaching 1.14 million people living with HIV-1 (PLWH) in 2021. Since mid-1990s, the HIV-1 epidemic in Russia has started to grow substantially due to the multiple HIV-1 outbreaks among persons who inject drugs (PWID) leading to expansion of the HIV-1 sub-subtype A6 (former Soviet Union (FSU) subtype A). In 2006, a local HIV-1 sub-epidemic caused by the distribution of novel genetic lineage CRF63_02A6 was identified in Siberia. In this study, we used a comprehensive dataset of CRF63_02A6 pol gene sequences to investigate the spatiotemporal dynamic of the HIV-1 CRF63_02A6 sub-epidemic. This study includes all the available CRF63_02A6 HIV-1 pol gene sequences from Los Alamos National Laboratory (LANL) HIV Sequence Database. The HIV-1 subtypes of those sequences were conferred using phylogenetic analysis, and two automated HIV-1 subtyping tools Stanford HIVdb Program and COMET. Ancestral state reconstruction and origin date were estimated using Nextstrain. Evolutionary rate and phylodynamic analysis were estimated using BEAST v 1.10.4. CRF63_02A6 was assigned for 872 pol gene sequences using phylogenetic analysis approach. Predominant number (n = 832; 95.4%) of those sequences were from Russia; the remaining 40 (4.6%) sequences were from countries of Central Asia. Out of 872 CRF63_02A6 sequences, the corresponding genetic variant was assigned for 75.7 and 79.8% of sequences by Stanford and COMET subtyping tools, respectively. Dated phylogenetic analysis of the CRF63_02A6 sequences showed that the virus most likely originated in Novosibirsk, Russia, in 2005. Over the last two decades CRF63_02A6 has been widely distributed across Russia and has been sporadically detected in countries of Central Asia. Introduction of new genetic variant into mature sub-subtype A6 and CRF02_AGFSU epidemics could promote the increase of viral genetic diversity and emergence of new recombinant forms. Further HIV-1 studies are needed due to a continuing rapid virus distribution. Also, the implementation of HIV-1 prevention programs is required to reduce HIV-1 transmission. This study also highlights the discrepancies in HIV-1 subtyping approaches. The reference lists of HIV-1 sequences implemented in widely used HIV-1 automated subtyping tools need to be updated to provide reliable results.
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