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      Exploring Dynamic Changes in HIV-1 Molecular Transmission Networks and Key Influencing Factors: Cross-Sectional Study

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          Abstract

          Background

          The HIV-1 molecular network is an innovative tool, using gene sequences to understand transmission attributes and complementing social and sexual network studies. While previous research focused on static network characteristics, recent studies’ emphasis on dynamic features enhances our understanding of real-time changes, offering insights for targeted interventions and efficient allocation of public health resources.

          Objective

          This study aims to identify the dynamic changes occurring in HIV-1 molecular transmission networks and analyze the primary influencing factors driving the dynamics of HIV-1 molecular networks.

          Methods

          We analyzed and compared the dynamic changes in the molecular network over a specific time period between the baseline and observed end point. The primary factors influencing the dynamic changes in the HIV-1 molecular network were identified through univariate analysis and multivariate analysis.

          Results

          A total of 955 HIV-1 polymerase fragments were successfully amplified from 1013 specimens; CRF01_AE and CRF07_BC were the predominant subtypes, accounting for 40.8% (n=390) and 33.6% (n=321) of the specimens, respectively. Through the analysis and comparison of the basic and terminal molecular networks, it was discovered that 144 sequences constituted static molecular networks, and 487 sequences contributed to the formation of dynamic molecular networks. The findings of the multivariate analysis indicated that the factors occupation as a student, floating population, Han ethnicity, engagement in occasional or multiple sexual partnerships, participation in anal sex, and being single were independent risk factors for the dynamic changes observed in the HIV-1 molecular network, and the odds ratio (OR; 95% CIs) values were 2.63 (1.54-4.47), 1.83 (1.17-2.84), 2.91 (1.09-7.79), 1.75 (1.06-2.90), 4.12 (2.48-6.87), 5.58 (2.43-12.80), and 2.10 (1.25-3.54), respectively. Heterosexuality and homosexuality seem to exhibit protective effects when compared to bisexuality, with OR values of 0.12 (95% CI 0.05-0.32) and 0.26 (95% CI 0.11-0.64), respectively. Additionally, the National Eight-Item score and sex education experience were also identified as protective factors against dynamic changes in the HIV-1 molecular network, with OR values of 0.12 (95% CI 0.05-0.32) and 0.26 (95% CI 0.11-0.64), respectively.

          Conclusions

          The HIV-1 molecular network analysis showed 144 sequences in static networks and 487 in dynamic networks. Multivariate analysis revealed that occupation as a student, floating population, Han ethnicity, and risky sexual behavior were independent risk factors for dynamic changes, while heterosexuality and homosexuality were protective compared to bisexuality. A higher National Eight-Item score and sex education experience were also protective factors. The identification of HIV dynamic molecular networks has provided valuable insights into the characteristics of individuals undergoing dynamic alterations. These findings contribute to a better understanding of HIV-1 transmission dynamics and could inform targeted prevention strategies.

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          Most cited references50

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          Cytoscape: a software environment for integrated models of biomolecular interaction networks.

          Cytoscape is an open source software project for integrating biomolecular interaction networks with high-throughput expression data and other molecular states into a unified conceptual framework. Although applicable to any system of molecular components and interactions, Cytoscape is most powerful when used in conjunction with large databases of protein-protein, protein-DNA, and genetic interactions that are increasingly available for humans and model organisms. Cytoscape's software Core provides basic functionality to layout and query the network; to visually integrate the network with expression profiles, phenotypes, and other molecular states; and to link the network to databases of functional annotations. The Core is extensible through a straightforward plug-in architecture, allowing rapid development of additional computational analyses and features. Several case studies of Cytoscape plug-ins are surveyed, including a search for interaction pathways correlating with changes in gene expression, a study of protein complexes involved in cellular recovery to DNA damage, inference of a combined physical/functional interaction network for Halobacterium, and an interface to detailed stochastic/kinetic gene regulatory models.
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            Transmission Network Parameters Estimated From HIV Sequences for a Nationwide Epidemic

            Background. Many studies of sexual behavior have shown that individuals vary greatly in their number of sexual partners over time, but it has proved difficult to obtain parameter estimates relating to the dynamics of human immunodeficiency virus (HIV) transmission except in small-scale contact tracing studies. Recent developments in molecular phylodynamics have provided new routes to obtain these parameter estimates, and current clinical practice provides suitable data for entire infected populations. Methods. A phylodynamic analysis was performed on partial pol gene sequences obtained for routine clinical care from 14 560 individuals, representing approximately 60% of the HIV-positive men who have sex with men (MSM) under care in the United Kingdom. Results. Among individuals linked to others in the data set, 29% are linked to only 1 individual, 41% are linked to 2–10 individuals, and 29% are linked to ≥10 individuals. The right-skewed degree distribution can be approximated by a power law, but the data are best fitted by a Waring distribution for all time depths. For time depths of 5–7 years, the distribution parameter ρ lies within the range that indicates infinite variance. Conclusions. The transmission network among UK MSM is characterized by preferential association such that a randomly distributed intervention would not be expected to stop the epidemic.
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              Social and Genetic Networks of HIV-1 Transmission in New York City

              Background Sexually transmitted infections spread across contact networks. Partner elicitation and notification are commonly used public health tools to identify, notify, and offer testing to persons linked in these contact networks. For HIV-1, a rapidly evolving pathogen with low per-contact transmission rates, viral genetic sequences are an additional source of data that can be used to infer or refine transmission networks. Methods and Findings The New York City Department of Health and Mental Hygiene interviews individuals newly diagnosed with HIV and elicits names of sexual and injection drug using partners. By law, the Department of Health also receives HIV sequences when these individuals enter healthcare and their physicians order resistance testing. Our study used both HIV sequence and partner naming data from 1342 HIV-infected persons in New York City between 2006 and 2012 to infer and compare sexual/drug-use named partner and genetic transmission networks. Using these networks, we determined a range of genetic distance thresholds suitable for identifying potential transmission partners. In 48% of cases, named partners were infected with genetically closely related viruses, compatible with but not necessarily representing or implying, direct transmission. Partner pairs linked through the genetic similarity of their HIV sequences were also linked by naming in 53% of cases. Persons who reported high-risk heterosexual contact were more likely to name at least one partner with a genetically similar virus than those reporting their risk as injection drug use or men who have sex with men. Conclusions We analyzed an unprecedentedly large and detailed partner tracing and HIV sequence dataset and determined an empirically justified range of genetic distance thresholds for identifying potential transmission partners. We conclude that genetic linkage provides more reliable evidence for identifying potential transmission partners than partner naming, highlighting the importance and complementarity of both epidemiological and molecular genetic surveillance for characterizing regional HIV-1 epidemics.
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                Author and article information

                Contributors
                Journal
                JMIR Public Health Surveill
                JMIR Public Health Surveill
                JPH
                JMIR Public Health and Surveillance
                JMIR Publications (Toronto, Canada )
                2369-2960
                2024
                29 May 2024
                : 10
                : e56593
                Affiliations
                [1 ] Department of Infection Management Nanjing Drum Tower Hospital Nanjing China
                [2 ] Children's Hospital of Nanjing Medical University Nanjing China
                [3 ] Nanjing Municipal Center for Disease Control and Prevention Nanjing China
                [4 ] School of Public Health Southeast University Nanjing China
                [5 ] Nanjing Qixia District Center for Disease Control and Prevention Nanjing China
                Author notes
                Corresponding Author: Wei Li weili126@ 123456126.com
                Author information
                https://orcid.org/0000-0003-0912-3755
                https://orcid.org/0009-0003-6000-5516
                https://orcid.org/0000-0003-3524-8180
                https://orcid.org/0000-0002-3343-8012
                https://orcid.org/0000-0003-4497-7916
                https://orcid.org/0000-0003-4344-4034
                https://orcid.org/0009-0006-4456-8660
                https://orcid.org/0000-0001-7763-5600
                https://orcid.org/0000-0003-0769-5805
                Article
                v10i1e56593
                10.2196/56593
                11170051
                38810253
                69992c68-8b71-4409-897a-226cdd677b22
                ©Yan He, Ying Tang, Qun Hua, Xin Li, You Ge, Yangyang Liu, Rong Tang, Ye Tian, Wei Li. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 29.05.2024.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Public Health and Surveillance, is properly cited. The complete bibliographic information, a link to the original publication on https://publichealth.jmir.org, as well as this copyright and license information must be included.

                History
                : 21 January 2024
                : 30 January 2024
                : 19 February 2024
                : 5 May 2024
                Categories
                Original Paper
                Original Paper

                hiv,dynamic,molecular transmission network,influence factors,hiv-1,molecular network,real-time analysis,transmission,nanjing,infection,gene distance,heterosexual,homosexual,dynamic alteration,dynamic alterations,risk factor

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