RESUMO
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.
RESUMO
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.