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      Pretreatment HIV Drug Resistance and the Molecular Transmission Network Among HIV-Positive Individuals in China in 2022: Multicenter Observational Study

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          Abstract

          Background

          Emerging HIV drug resistance caused by increased usage of antiretroviral drugs (ARV) could jeopardize the success of standardized HIV management protocols in resource-limited settings.

          Objective

          We aimed to characterize pretreatment HIV drug resistance (PDR) among HIV-positive individuals and risk factors in China in 2022.

          Methods

          This cross-sectional study was conducted using 2-stage systematic sampling according to the World Health Organization’s surveillance guidelines in 8 provincial-level administrative divisions in 2022. Demographic information and plasma samples were obtained from study participants. PDR was analyzed using the Stanford HIV drug resistance database, and the Tamura-Nei 93 model in HIV-TRACE was used to calculate pairwise matches with a genetic distance of 0.01 substitutions per site. Logistic regression was used to identify and estimate factors associated with PDR.

          Results

          PDR testing was conducted on 2568 participants in 2022. Of the participants, 34.8% (n=893) were aged 30-49 years, 81.4% (n=2091) were male, and 3.2% (n=81) had prior ARV exposure. The prevalence of PDR to protease and reverse transcriptase regions, nonnucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 7.4% (n=190), 6.3% (n=163), 1.2% (n=32), and 0.2% (n=5), respectively. Yunnan, Jilin, and Zhejiang had much higher PDR incidence than did Sichuan. The prevalence of nonnucleoside reverse transcriptase inhibitor–related drug resistance was 6.1% (n=157) for efavirenz and 6.3% (n=163) for nevirapine. Multivariable logistic regression models indicated that participants who had prior ARV exposure (odds ratio [OR] 7.45, 95% CI 4.50-12.34) and the CRF55_01B HIV subtype (OR 2.61, 95% CI 1.41-4.83) were significantly associated with PDR. Among 618 (24.2%) sequences (nodes) associated with 253 molecular transmission clusters (size range 2-13), drug resistance mutation sites included K103, E138, V179, P225, V106, V108, L210, T215, P225, K238, and A98.

          Conclusions

          The overall prevalence of PDR in China in 2022 was modest. Targeted genotypic PDR testing and medication compliance interventions must be urgently expanded to address PDR among newly diagnosed people living with HIV in China.

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          Most cited references47

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          HIV-TRACE (TRAnsmission Cluster Engine): a Tool for Large Scale Molecular Epidemiology of HIV-1 and Other Rapidly Evolving Pathogens.

          In modern applications of molecular epidemiology, genetic sequence data are routinely used to identify clusters of transmission in rapidly evolving pathogens, most notably HIV-1. Traditional 'shoe-leather' epidemiology infers transmission clusters by tracing chains of partners sharing epidemiological connections (e.g., sexual contact). Here, we present a computational tool for identifying a molecular transmission analog of such clusters: HIV-TRACE (TRAnsmission Cluster Engine). HIV-TRACE implements an approach inspired by traditional epidemiology, by identifying chains of partners whose viral genetic relatedness imply direct or indirect epidemiological connections. Molecular transmission clusters are constructed using codon-aware pairwise alignment to a reference sequence followed by pairwise genetic distance estimation among all sequences. This approach is computationally tractable and is capable of identifying HIV-1 transmission clusters in large surveillance databases comprising tens or hundreds of thousands of sequences in near real time, that is, on the order of minutes to hours. HIV-TRACE is available at www.hivtrace.org and from www.github.com/veg/hivtrace, along with the accompanying result visualization module from www.github.com/veg/hivtrace-viz. Importantly, the approach underlying HIV-TRACE is not limited to the study of HIV-1 and can be applied to study outbreaks and epidemics of other rapidly evolving pathogens.
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            HAART in HIV/AIDS Treatments, Future Trends.

            AIDS (acquired immune deficient syndrome) is a deadly human viral infectious disease caused by HIV (human immune-deficient virus) infection. Almost every AIDS patient losses his/her life before mid 1990s. AIDS was once the 1st disease killer in US (1993). After one decade hard work, antiviral drug cocktails-high active anti-retroviral therapy (HAART) have been invented for almost all HIV infection treatments. Due to the invention of HAART, 80-90% HIV/AIDS patients still effectively response to HAART for deadly AIDS episode controls and life saving. Yet, this type of HIV therapeutics is incurable. HIV/AIDS patients need to take HAART medications regularly and even life-long. To counteract this therapeutic drawback, more revolutionary efforts (different angles of therapeutic modes/attempts) are urgently needed. In this article, the major progresses and drawbacks of HIV/AIDS chemotherapy (HAART) to HIV/AIDS patients have been discussed. Future trends (updating pathogenesis study, next generations of drug developments, new drug target discovery, different scientific disciplinary and so on) are highlighted.
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              Trend of HIV-1 drug resistance in China: A systematic review and meta-analysis of data accumulated over 17 years (2001–2017)

              Background The emergence and spread of HIV-1 drug resistance may compromise HIV control globally. In response to HIV/AIDS epidemic, China launched national HIV/AIDS treatment program in 2003, and started to accumulate drug resistance data since 2001. In this study we aimed to assess the level, trend and distribution of HIV-1 drug resistance during a period of 17 years from 2001 to 2017, and to characterize crucial drug resistance mutations. Methods We systematically reviewed 4737 studies published between January 1, 2001 and March 31, 2019 in PubMed, Embase, China National Knowledge Infrastructure (CNKI), WanFang Database, Web of Science, conference abstracts from the Chinese Medical Association and the Chinese AIDS Academic Conferences, and selected 170 studies that met our study criteria. To assess the prevalence of drug resistance in whole country or a local region, we performed pooled analyses of raw data. The transformed proportions were pooled using the inverse variance fixed effects methods or the DerSimonian-Laired random effects methods. The temporal trend of transmitted drug resistance (TDR) was determined using generalized additive model implemented in the Mgcv version 1.8 package. HIV-1 genotypic resistance was analyzed using the Stanford HIVdb algorithm. Findings We assembled 218 datasets from 170 selected studies (129 in Chinese and 41 in English), covering 21,451 ART-naïve and 30,475 ART-treated individuals with HIV-1 infection. The pooled prevalence of TDR was 3.0% (95%CI: 2.8–3.2), including 0.7% (95%CI: 0.4–1.0), 1.4% (95%CI: 1.3–1.6) and 0.5% (95%CI: 0.4–0.6) for nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI (NNRTI) and protease inhibitor (PI) resistance, respectively. The acquired drug resistance (ADR) prevalence was 44.7% (95%CI: 39.3–50.2), including 31.4% (95%CI: 28.2–34.6), 39.5% (95%CI: 35.6–43.5) and 1.0% (95%CI: 0.8–1.2) for NRTI, NNRTI and PI resistance, respectively. TDR and ADR prevalence had characteristic regional patterns. The worst prevalence of drug resistance occurred in Central China, and higher ADR prevalence occurred in South China than North China. TDR in whole country has risen since 2012, and this rise was driven mainly by NNRTI resistance. One NRTI-associated (M184V/I) and three NNRTI-associated (K103N/S, Y181C/I and G190A/S) mutations had high percentages in ART-naïve and ART-treated individuals, and these mutations conferred high-level resistance to 3TC, EFV and/or NVP. Interpretation These findings suggest that the current available first-line ART regimens containing 3TC and/or EFV or NVP need to be revised. In addition, scale-up of multiple viral load measurements per year and drug resistance testing prior to ART initiation are recommended. Furthermore, implementation of pre-treatment education and counseling to improve patient adherence to ART is encouraged. Funding This work was supported by grants from the National Natural Science Foundation of China (81672033, U1302224, and 81271888) and Open Research Fund Program of the State Key Laboratory of Virology of China (2019IOV002).
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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
                2023
                17 November 2023
                : 9
                : e50894
                Affiliations
                [1 ] National Center for AIDS/STD Control and Prevention (NCAIDS) Chinese Center for Disease Control and Prevention (China CDC) Beijing China
                [2 ] Sichuan Nursing Vocational College Chengdu China
                [3 ] Department of Public Health The University of Texas at San Antonio San Antonio, TX United States
                Author notes
                Corresponding Author: Yuhua Ruan ruanyuhua92@ 123456163.com
                Author information
                https://orcid.org/0009-0001-6466-1823
                https://orcid.org/0009-0004-5977-2328
                https://orcid.org/0009-0008-1144-6995
                https://orcid.org/0009-0007-5048-6394
                https://orcid.org/0009-0008-2134-1601
                https://orcid.org/0000-0002-7328-0205
                https://orcid.org/0009-0001-2821-1972
                https://orcid.org/0009-0005-5721-4100
                https://orcid.org/0009-0004-6849-4358
                https://orcid.org/0009-0006-9547-332X
                https://orcid.org/0009-0006-7592-9473
                https://orcid.org/0009-0001-0324-1796
                https://orcid.org/0000-0003-3880-4744
                https://orcid.org/0000-0003-4995-1440
                https://orcid.org/0000-0003-1596-8033
                https://orcid.org/0000-0003-3612-7508
                https://orcid.org/0000-0002-4177-6038
                https://orcid.org/0000-0003-2346-9154
                https://orcid.org/0000-0002-3067-0908
                Article
                v9i1e50894
                10.2196/50894
                10692882
                37976080
                3bc9d281-c438-4c33-b112-c8448c57bba2
                ©Hongli Chen, Jingjing Hao, Jing Hu, Chang Song, Yesheng Zhou, Miaomiao Li, Jin Chen, Xiu Liu, Dong Wang, Xiaoshan Xu, Peixian Xin, Jiaxin Zhang, Lingjie Liao, Yi Feng, Dan Li, Stephen W Pan, Yiming Shao, Yuhua Ruan, Hui Xing. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 17.11.2023.

                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
                : 17 July 2023
                : 23 August 2023
                : 10 September 2023
                : 6 October 2023
                Categories
                Original Paper
                Original Paper

                hiv,human immunodeficiency virus,mutation,pretreatment drug resistance,risk factors,molecular transmission network

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