In China, human immunodeficiency virus (HIV) poses a significant challenge to older heterosexual adults. This study explored the transmission dynamics of HIV infection among older adults in northern Zhejiang Province, China using phylogenetic analysis and transmission networks. HIV pol sequences without any antiretroviral therapy were obtained from newly diagnosed HIV-positive patients in Huzhou between 2017 and 2022. Pairwise genetic distances between sequences were calculated using HIV Trace based on the Tamura-Nei 93 method. The transmission network was constructed using Cytoscape v3.9.1. The effective reproductive number (Re) of each large cluster was estimated using the birth-death skyline model in BEAST v2.4.2. Multivariate logistic regression was performed to identify factors associated with clustering using R v4.4.3 software. A total of 931 HIV pol sequences were successfully obtained, of which CRF07_BC (51.7
PURPOSE:To understand the geographic origins, transmission hotspots, and drug resistance mutations (DRMs) of HIV-1 CRF08_BC in Zhejiang Province, China. METHODS:This study analyzed HIV-1 CRF08_BC pol sequences collected between 2020 and 2023. Bayesian inference was employed to investigate temporal epidemic trends, while HIV-TRACE and MCODE were used to identify transmission clusters (TCs), key hotspots and super-spreaders. DRMs associated with CRF08_BC were also characterized. Additionally, demographic data were integrated with these findings, allowing for a description of the transmission dynamics. RESULTS:This study revealed that CRF08_BC strains in Zhejiang likely originated from Guangxi, with significant transmission among individuals aged 50 and older, particularly those with low educational levels. Molecular transmission analysis showed that 58.9% of CRF08_BC sequences were in TCs, with geographic concentrations in Taizhou (TZ) and Lishui (LS). 14 large clusters maintained effective reproductive numbers (Re) above 1, representing considerable epidemic growth. Hangzhou (HZ) emerged as a key transmission hub, with 10 TCs showing active transmission. LS established strong epidemiological links with HZ, Ningbo (NB), Taizhou (TZ), and Wenzhou (WZ), creating a pattern of viral spread radiating from LS to surrounding areas. DRMs were identified in 76 cases (6.0%), with NNRTI and NRTI mutations exhibiting distinct geographic clustering. CONCLUSIONS:The CRF08_BC strains in Zhejiang likely originated from Guangxi and are mainly found in individuals aged 50 and older with low education. The current epidemic hotspots are in TZ and LS, where NNRTI and NRTI mutations are clustered, significantly impacting treatment efficacy.
This study aimed to conduct a comprehensive molecular epidemiology study of major HIV-1 subtypes in developed Eastern China (Zhejiang Province). Plasma samples and epidemiological information were collected from 4180 newly diagnosed HIV-1 positive patients in Zhejiang Province in 2021. Pol sequences were obtained to determine the subtypes via multiple analytical tools. HIV-1 molecular networks were constructed on the basis of genetic distances to analyze transmission patterns among major subtypes. Furthermore, the birth-death skyline (BDSKY) model was utilized to estimate the transmission risks associated with large clusters (LCs). In 4180 patients, 3699 (88.49
HIV drug resistance compromises the ability of anti-retroviral therapy (ART) to suppress viral replication, resulting in treatment failure. This study investigates the prevalence of pre-treatment drug resistance (PDR) in newly diagnosed individuals in a prosperous city (Wenzhou) in Southeastern China. A cross-sectional investigation was carried out among 473 newly diagnosed ART-naive HIV-1-infected individuals between January and December 2022. The protease–reverse transcriptase (PR-RT) region and integrase (IN) region of HIV-1 were amplified by two separately nested PCRs, followed by sequencing. Drug resistance mutations (DRMs) and drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and integrase strand transfer inhibitors (INSTIs) were analyzed. The PDR prevalence was 6.5% [95% CI: 4.4–9.1] for any anti-retroviral drug, 0.9% [95% CI: 0.3–2.3] for NRTIs, 4.1% [95% CI: 2.5–6.5] for NNRTIs, 1.8% [95% CI: 0.8–3.6] for PIs and 0.5% [95% CI: 0.1–1.8] for INSTIs. According to the subtyping results of the PR-RT region, 11 different subtypes and 31 unique recombinant forms (URFs) were found. CRF07_BC was the dominant subtype (53.7%, 233/434), followed by CRF01_AE (25.3%, 110/434). V179D (1.6%) and K103N (1.4%) were the most predominant types of NNRTI DRMs. Q58E (1.2%) and M184V (0.7%) were the most frequent PI DRMs and NRTI DRMs, respectively. The INSTI-related DRMs Y143S (causes high-level resistance to RAL) and G163K (causes low-level resistance to EVG and RAL) were found in one patient each. Given the relatively high PDR prevalence of NNRTI (4.1%), non-NNRTI-based ART may be preferred in the future. It is recommended to include genotypic resistance testing before starting ART in regions where feasible.
Objectives: This study aimed to establish a collaborative approach to quantify local HIV transmission, which is an issue of great concern to public health. Methods: We linked HIV-1 pol gene sequences to demographic information and epidemiological investi-gations in Hangzhou (a central city in East China). We estimated local acquisition rates from a collabora-tion of molecular network analysis (with a distance-based approach) and epidemiological investigations. Results: Among 1064 newly diagnosed patients with HIV, 857 pol sequences were acquired and sub-sequently analyzed. Multiple subtypes were identified, with circulating recombinant form (CRF)07_BC (42.5%) and CRF01_AE (39.2%) predominating, followed by 13 other subtypes and 26 unique recombinant forms. By integrating the molecular network analysis and epidemiological investigations, we estimated that the proportion of local infection was 63.2%. The multivariable analyses revealed that individuals in clusters were more likely to be local residents, be aged 50 years or older, work as farmers, and have a higher first cluster of differentiation 4 count level ( P < 0.05). The proportions of local acquisitions over 70% were observed in local residents (79.9%, 242/303), individuals aged 50 years or older (73.6%, 181/246), and farmers (75.6%, 99/131). Conclusion: The molecular network analysis can augment traditional HIV epidemic surveillance. This study establishes a paradigm for quantifying local HIV transmission for generalization in other areas.(c) 2022 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )
As a retrovirus with high recombination and mutation rate, HIV targets CD4+ T lymphocytes, causing damage to the body's immune system and eventually leading to severe immune function defects. Different subtypes of the HIV virus exhibit significant sequence differences in their structural and regulatory genes, and this diversity is closely related to etiology, transmission, diagnosis, drug therapy, disease progression, and vaccine development. As a country with the largest number of HIV subtypes, rapid and accurate typing of the HIV virus holds great significance for China's efforts in disease prevention and control. This study provides a comprehensive reveiw of domestic and international HIV genotyping methods, and summarizes the clinical significance of different subtypes in order to provide reference for further research.
We aimed to elucidate the characteristics of HIV molecular epidemiology and identify transmission hubs in eastern China using genetic transmission network and lineage analyses. HIV-TRACE was used to infer putative relationships. Across the range of epidemiologically-plausible genetic distance (GD) thresholds (0.1–2.0%), a sensitivity analysis was performed to determine the optimal threshold, generating the maximum number of transmission clusters and providing reliable resolution without merging different small clusters into a single large cluster. Characteristics of genetically linked individuals were analyzed using logistic regression. Assortativity (shared characteristics) analysis was performed to infer shared attributes between putative partners. 1,993 persons living with HIV-1 were enrolled. The determined GD thresholds within subtypes CRF07_BC, CRF01_AE, and B were 0.5%, 1.2%, and 1.7%, respectively, and 826 of 1,993 (41.4%) sequences were linked with at least one other sequence, forming 188 transmission clusters of 2–80 sequences. Clustering rates for the main subtypes CRF01_AE, CRF07_BC, and B were 50.9% (523/1027), 34.2% (256/749), and 32.1% (25/78), respectively. Median cluster sizes of these subtypes were 2 (2–52, n = 523), 2 (2–80, n = 256), and 3 (2–6, n = 25), respectively. Subtypes in individuals diagnosed and residing in Hangzhou city (OR = 1.423, 95% CI: 1.168–1.734) and men who have sex with men (MSM) were more likely to cluster. Assortativity analysis revealed individuals were more likely to be genetically linked to individuals from the same age group (AI age = 0.090, P <0.001) and the same area of residency in Zhejiang (AI city = 0.078, P <0.001). Additionally, students living with HIV were more likely to be linked with students than show a random distribution (AI student = 0.740, P <0.01). These results highlight the importance of Hangzhou City in the regional epidemic and show that MSM comprise the population rapidly transmitting HIV in Zhejiang Province. We also provide a molecular epidemiology framework for improving our understanding of HIV transmission dynamics in eastern China.
HIV/AIDS患者的实体器官移植在国外已快速发展,但我国实施器官移植手术较少.本文通过回顾当前HIV/AIDS患者的肺移植开展情况,从抗排斥反应、高效抗反转录病毒治疗、术后并发症及生存状况等多个角度讨论我国开展HIV/AIDS患者肺移植手术的可行性.
Identification of human immunodeficiency virus (HIV) transmission networks is a critical step in the public health response; however, it is challenging to achieve this through traditional epidemiological surveys alone. The molecular network approach can provide more accurate information for understanding HIV outbreaks and bring targeted interventions into reality. Based on the current global development of the concept of the molecular network, Chinese scientists have in recent years explored the applications of molecular networks for understanding the HIV-1 transmission trends, for identifying the population acquiring priority interventions, and for evaluating the targeted intervention effectiveness, In this review, we focus on research progress by Chinese scientists in the field of molecular networks and put forward some suggestions for future research of molecular networks.
In this study, we conducted a detailed molecular epidemiological analysis of HIV-1 epidemic strains in various sexual risk behaviour groups in a developed area in eastern China based on phylogenetic inference, molecular transmission networks, and Bayesian analyses. A total of 1083 pol sequences (91.23%, 1083/1187) from newly diagnosed HIV-1-positive patients from 2017 to 2020 were successfully obtained and involved thirteen HIV-1 subtypes, in which the major HIV-1 subtypes were CRF07_BC (36.10%, 391/1083) and CRF01_AE (34.63%, 375/1083). 485 individuals (44.78%,485/1083) formed 146 clusters in the network. Of which CRF07_BC showed extensive clustering driven by men who have sex with men (MSM) within larger networks, CRF01_AE and other subtypes were generally driven by small clusters (SCs) and medium clusters (MCs) among various risk groups. Through Sankey diagrams, the MSM group infected with CRF07_BC had a greater impact on the non-commercial heterosexual group among all cross-risk groups. In addition, a higher number of key individuals infected with CRF07_BC (40.22%, 74/127), suggests the crucial role of CRF07_BC-infected individuals as a local epidemic driver in the context of a mixed HIV-1 epidemic. Further Bayesian analysis confirmed that CRF07_BC was introduced into Jiaxing city from other provinces multiple times and spread rapidly among MSM and heterosexual individuals. Overall, our study provided some insights and information to explore the local transmission dynamics of HIV-1 epidemic strains involving various sexual risk groups, and emphasize that it is necessary to conduct in-depth research and precise intervention targeting key clusters/ individuals to effectively block the continued transmission of AIDS.
Precise identification of HIV transmission among populations is a key step in public health responses. However, the HIV transmission network is usually difficult to determine. HIV molecular networks can be determined by phylogenetic approach, genetic distance-based approach, and a combination of both approaches. These approaches are increasingly used to identify transmission networks among populations, reconstruct the history of HIV spread, monitor the dynamics of HIV transmission, guide targeted intervention on key subpopulations, and assess the effects of interventions. Simulation and retrospective studies have demonstrated that these molecular network-based interventions are more cost-effective than random or traditional interventions. However, we still need to address several challenges to improve the practice of molecular network-guided targeting interventions to finally end the HIV epidemic. The data remain limited or difficult to obtain, and more automatic real-time tools are required. In addition, molecular and social networks must be combined, and technical parameters and ethnic issues warrant further studies.
The HIV epidemic in China accounts for 3% of the global HIV incidence. We compared the patterns and determinants of interprovincial spread of the five most prevalent circulating types. HIV pol sequences sampled across China were used to identify relevant transmission networks of the five most relevant HIV-1 types (B and circulating recombinant forms [CRFs] CRF01_AE, CRF07_BC, CRF08_BC, and CRF55_01B) in China. From these, the dispersal history across provinces was inferred. A generalized linear model (GLM) was used to test the association between migration rates among provinces and several measures of human mobility. A total of 10,707 sequences were collected between 2004 and 2017 across 26 provinces, among which 1,962 are newly reported here. A mean of 18 (minimum and maximum, 1 and 54) independent transmission networks involving up to 17 provinces were identified. Discrete phylogeographic analysis largely recapitulates the documented spread of the HIV types, which in turn, mirrors within-China population migration flows to a large extent. In line with the different spatiotemporal spread dynamics, the identified drivers thereof were also heterogeneous but are consistent with a central role of human mobility. The comparative analysis of the dispersal dynamics of the five main HIV types circulating in China suggests a key role of large population centers and developed transportation infrastructures as hubs of HIV dispersal. This advocates for coordinated public health efforts in addition to local targeted interventions. IMPORTANCE While traditional epidemiological studies are of great interest in describing the dynamics of epidemics, they struggle to fully capture the geospatial dynamics and factors driving the dispersal of pathogens like HIV as they have difficulties capturing linkages between infections. To overcome this, we used a discrete phylogeographic approach coupled to a generalized linear model extension to characterize the dynamics and drivers of the across-province spread of the five main HIV types circulating in China. Our results indicate that large urbanized areas with dense populations and developed transportation infrastructures are facilitators of HIV dispersal throughout China and highlight the need to consider harmonized country-wide public policies to control local HIV epidemics.
BACKGROUND:To infer transmission direction of a HIV transmission chain is helpful not only in legal jurisdiction but also in precise intervention to prevent HIV spread. Recently, the direction of transmission is inferred by whether paraphyletic-monophyletic (PM) or a combination of paraphyletic and polyphyletic (PP) topologies is observed or not between the sequences of source and recipient in the phylogenetic tree. However, paraphyly between them often declines over time and may disappear between spouses due to bidirectional transmission after primary infection. In this study, our aim is to test the reliability of inferring HIV transmission direction between epidemiologically linked HIV-1 positive couples using whether or not paraphyly is observed in phylogenetic tree.METHODS:HIV quasi-species were sequenced using PCR product clones, and then Bayesian analysis of molecular sequences with MCMC was employed to construct phylogenetic relationship of env, gag, pol gene fragments of HIV-1 positive couples using BEAST software.RESULTS:Our results showed that all sequences of seven couples except pol sequences of couple 12 and 13 form their own monophyletic cluster in phylogenetic tree including the closest control sequences from GenBank or other studies on local samples, which are supported by significant Bayesian posterior probabilities more than 0.9932. Of seven couples, paraphyly is only observed in phylogenetic tree constructed with env and pol gene sequences of three couples and gag gene sequences of four couples. Paraphyly is not observed in half of HIV positive couples. Pol sequences of couple 13 is separated by Blast selected controls; pol sequences of couple 12 in phylogenetic tree is supported by a lower Bayesian posterior value.CONCLUSION:Paraphyly relationship between sequences of donator and recipient is only observed among partial HIV-1 positive couples with epidemiological link. Phylogenetic relationship is not always the same when various gene regions of HIV are used to conduct phylogenetic analysis. The combination of phylogenetic analysis based on various gene regions of HIV and enough epidemiology investigation is essential when inferring transmission direction of HIV in a transmission chain or in one couple. However, while observed paraphyly can be used to infer transmission direction in HIV-1 positive couple, no observed paraphyly cannot deny it.
本文系统地综述了近年来国内外艾滋病分子流行病学研究和实践方面的进展,主要从三个方面阐述了全球和中国HIV-1基因亚型和新型重组型病毒演变的现状、特点和趋势,以及正在发展的可助力于精准干预艾滋病流行的分子传播网络的最新研究进展,包括全球HIV-1亚型多样性和分布地域性、我国HIV-1亚型此消彼长、新型重组病毒频繁发生和HIV分子传播网络研究进入实践阶段.本文明确指出了HIV-1亚型和重组病毒多样性是阻碍遏制HIV流行的关键因素,并强调了基于分子簇的精准干预在助力控制艾滋病流行中的重要意义.本文将为从事艾滋病防治事业的公共卫生专业人员、医生以及实验室工作人员提供较新的信息,供读者进一步学习和参考.
The prevalence and incidence of human immunodeficiency virus type 1 (HIV-1) among men who have sex with men (MSM) are on the rise throughout China. With a large population of MSM, Jiangsu Province is facing an escalating HIV-1 epidemic. The aim of this study was to explore the phylogenetic and temporal dynamics of HIV-1 CRF01_AE and CRF07_BC among antiretroviral therapy (ART)-naive MSM recently infected with HIV-1 in Jiangsu Province. We recruited MSM in Jiangsu Province (Suzhou, Wuxi, Nantong, Taizhou and Yancheng) 2012 to 2015. We collected information on demographics and sexual behaviors and a blood sample for HIV genome RNA extraction, RT-PCR amplification, and DNA sequencing. Multiple alignments were made using Gene Cutter, with the selected reference sequences of various subtypes/recombinants from the Los Alamos HIV-1 database. Phylogenetic and Bayesian evolutionary analysis was performed by MEGA version 6.0, Fasttree v2.1.7. and BEAST v1.6.2. Categorical variables were analyzed using chi(2) test (or Fisher exact test where necessary). chi(2) test with trend was used to assess the evolution of HIV-1 subtype distribution over time. All data were analyzed using SPSS20.0 software package (IBM Company, New York, NY). HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01_AE (60.06%), CRF07_BC (22.29%), subtype B (5.88%), CRF67_01B (5.26%), CRF68_01B (2.79%), CRF55_01B (1.55%), CRF59_01B (0.93%), and CRF08_BC (0.62%). Two unique recombination forms (URFs) (0.62%) were also detected. Four epidemic clusters and 1 major cluster in CRF01_AE and CRF07_BC were identified. The introduction of CRF01_AE strain (2001) was earlier than CRF07_BC strain (2004) into MSM resided in Jiangsu based on the time of the most recent common ancestor. Our study demonstrated HIV-1 subtype diversity among ART-naive MSM recently infected with HIV-1 in Jiangsu. We first depicted the spatiotemporal dynamics, traced the dates of origin for the HIV-1 CRF01_AE/07_BC strains and made inference for the effective population size among newly infected ART-naive MSM in Jiangsu from 2012 to 2015. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster would be of great value to the monitoring of the epidemic and control of transmission, improvement of antiretroviral therapy strategies, and design of vaccines.
We aimed to investigate the molecular epidemic characteristics and viral transmission patterns of HIV-1 in a typical labor export area, Guangyuan city, China. Based on conducting phylogenetic trees and molecular transmission networks, a phylogenetic analysis was performed on HIV-1 pol sequences obtained from 211 migrant-history workers, 83 non-migrant-history individuals, and 21 migrant-history unknown individuals between January, 2012 and February, 2017 in Guangyuan city. Phylogenetic analysis revealed that CRF07_BC (48.3%, n = 152) and CRF01_AE (33.3%, n = 105) were the dominant strains in Guangyuan city, and circulated by multiple lineages with various epidemic characteristics. Geographic network analysis showed that Guangyuan city-related sequences with 20.3% CRF07_BC and 28.3% CRF01_AE were linked to that of other provinces, compared to that with 1.7% CRF07_BC and 5.0% CRF01_AE in cities of Sichuan. Molecular transmission network analysis further illustrated that migrant-history workers linked more sequences from other provinces than non-migrant-history individuals in both CRF07_BC (29.3% versus 0.0%, P = 0.013) and CRF01_AE (40.5% versus 10.0%, P = 0.001) networks. Our results highlighted that migrant-history workers in recent year played a vital role in fueling HIV-1 epidemic in Guangyuan city. Molecular transmission network analysis could be a useful approach for disclosing the transmission mechanism of HIV, which should be used in prevention and intervention efforts.
社会流行病学调查对揭示1型艾滋病病毒(HIV-1)传播特征起到了重要作用,但也存在调查成本高及可信性不足的缺点.随着系统进化分析方法学的进步以及快速增加的HIV-1序列,基于HIV-1基因信息的分子传播网络分析近年来快速发展并被广泛运用.本文综述了该分析方法的基本原理、运用现状、判定方法及参数选择,旨在为该方法的进一步发展和运用提供借鉴.
On Nov 28, 2018, during the Second International Summit on Human Genome Editing in Hong Kong, He Jiankui and colleagues from China claimed that they have edited the human embryonic genome to disable the CCR5 gene in work that resulted in the birth of twin sisters.1China NewsHe Jiankui appeared in Hong Kong: results disclosing and question answer.China News. Nov 28, 2018; (in Chinese).http://news.sina.com.cn/o/2018-11-28/doc-ihmutuec4407821.shtmlDate accessed: November 29, 2018Google Scholar The announcement generated serious concerns relating to scientific ethics. As Chinese professionals engaged in HIV research and prevention, we strongly oppose genome editing on healthy human germline cells and embryos for reproductive purposes and HIV prevention. We call for policies and regulatory authorities to thoroughly investigate this incident and to fully protect the privacy and rights of the babies and associated family members. We commend the Chinese Government agencies in swiftly halting such experiments and initiating a series of nationwide efforts to safeguard the highest scientific and ethical standards in genome editing research. Rules and regulations must be implemented for the proper evaluation and oversight on genome editing technology for human use. In support of stable and sustained scientific development in China and other countries, we make the following statements. First, from a scientific ethical perspective, we oppose genome editing of healthy human germline cells and embryos for reproductive use. Rigorous scientific and ethical assessments are also required for genome editing of germline cells and embryos with the intention of treating severe genetic diseases.2Nuffield Council on BioethicsGenome editing and human reproduction. Nuffield Council on Bioethics, London2018Google Scholar, 3National Academies of Sciences, Engineering, and MedicineHuman genome editing: science, ethics, and governance. The National Academies Press, Washington, DC2017Google Scholar, 4Chinese Ministry of Health and Ministry of Science and TechnologyEthical Guidance on Human Embryonic Cell Research, Regulations on Biomedical Research related to Human Studies, Safety Regulations on Biotechnology Research. Chinese Ministry of Health and Ministry of Science and Technology, Beijing2003Google Scholar All research should be balanced against the severity of the disease to ensure that a safe risk–benefit ratio to study volunteers and highest ethical standards are achieved. China and international regulatory agencies should make renewed and enhanced efforts to ensure the proper regulation and implementation of genome editing technology to take account of all appropriate scientific, ethical, and societal contexts.2Nuffield Council on BioethicsGenome editing and human reproduction. Nuffield Council on Bioethics, London2018Google Scholar, 3National Academies of Sciences, Engineering, and MedicineHuman genome editing: science, ethics, and governance. The National Academies Press, Washington, DC2017Google Scholar, 4Chinese Ministry of Health and Ministry of Science and TechnologyEthical Guidance on Human Embryonic Cell Research, Regulations on Biomedical Research related to Human Studies, Safety Regulations on Biotechnology Research. Chinese Ministry of Health and Ministry of Science and Technology, Beijing2003Google Scholar Those individuals and associated institutions that violate these principles and regulations should be held accountable. Second, there are clear and strict regulations and institutional review processes in Europe and the USA on human genome editing technology.2Nuffield Council on BioethicsGenome editing and human reproduction. Nuffield Council on Bioethics, London2018Google Scholar, 3National Academies of Sciences, Engineering, and MedicineHuman genome editing: science, ethics, and governance. The National Academies Press, Washington, DC2017Google Scholar China has introduced scientific and bioethical regulations and recommendations on safety and applications of biotechnologies to human reproduction since 2003.4Chinese Ministry of Health and Ministry of Science and TechnologyEthical Guidance on Human Embryonic Cell Research, Regulations on Biomedical Research related to Human Studies, Safety Regulations on Biotechnology Research. Chinese Ministry of Health and Ministry of Science and Technology, Beijing2003Google Scholar However, government policies and regulatory authorities worldwide must keep pace with developments in this technology and formulate effective regulatory measures in a timely way. Researchers and their institutions worldwide must safeguard the highest scientific ethical standards in scientific research and improve their legal, scientific, and ethical awareness. The safety and effectiveness of human genome editing technology must be evaluated in a regulated environment with appropriate oversight. Third, human genome editing technology still requires improvement and refinement. There are likely to be unintended consequences of this technology, largely involving off-target and unintended side-effects5Cong L Zhang F Genome engineering using CRISPR-Cas9 system.Methods Mol Biol. 2015; 1239: 197-217Crossref PubMed Scopus (177) Google Scholar that mean extreme caution is needed if this technology is to be used in clinical trials and practice. Fourth, the CCR5 gene has a key role in maintaining proper physiological and immunological functions of the cell.6Lusso P HIV and the chemokine system: 10 years later.EMBO J. 2006; 25: 447-456Crossref PubMed Scopus (172) Google Scholar Genetically knocking out CCR5 in healthy human embryos has no scientific basis, could have severe adverse effects, and is likely to have unpredictable consequences. Fifth, HIV is highly mutable and CCR5 is only one of the co-receptors for HIV entry.6Lusso P HIV and the chemokine system: 10 years later.EMBO J. 2006; 25: 447-456Crossref PubMed Scopus (172) Google Scholar Therefore, disabling the CCR5 gene would not completely prevent HIV infection. Finally, proven effective and affordable strategies already exist for the prevention of perinatal transmission of HIV, including antiretroviral drugs, safe delivery, and alternative feeding.7WHOGlobal guidance on criteria and process for validation: elimination of mother-to-child transmission of HIV and syphilis. World Health Organization, Geneva2014Google Scholar Embryonic knockout CCR5 provides no benefit but is likely to have uncontrollable risks to the babies and their future health. Chinese scientists are committed to scientific advancement and social development. In exploring new areas and driving innovation we must always safeguard the highest ethical standards in our research. The proper balance between risks and benefits must be evaluated and managed to ensure the innovative human genome editing technology can be safely and effectively applied for future human use. We have an obligation and responsibility to provide the best quality of care to our community while pushing the boundary of innovation to fight against human diseases. We declare no competing interests. Download .pdf (.07 MB) Help with pdf files Supplementary appendix Department of ErrorZhang L, Zhong P, Zhai X, et al. Open letter from Chinese HIV professionals on human genome editing. Lancet 2018; published online Nov 30. http://dx.doi.org/10.1016/S0140-6736(18)33082-4. The web appendix of this Correspondence has been corrected as of Dec 5, 2018. Full-Text PDF
Objective: To investigate the viral genetic evolution, spatial origins and patterns of transmission of HIV-1 subtype B in Shanghai, China.Methods: A total of 242 Shanghai subtype B and 1519 reference pol sequences were subjected to phylogenetic inference and genetic transmission network analyses.Results: Phylogenetic analysis revealed that subtype B strains circulating in Shanghai were genetically diverse and closely associated with viral sequence lineages in Beijing (76 of 242 [31.4%]), Central China (Henan/ Hebei/ Hunan/ Hubei) (43 of 242 [17.8%]), Chinese Taiwan (20 of 242 [8.3%]), Japan (6 of 242 [2.5%]), and Korea (7 of 242 [2.9%]), suggesting multipleintroductions into Shanghai from mainland China and Taiwan, Japan, and Korea. Interestingly, a monophyletic Shanghai lineage (SH-L) (36 of 242 [ 14.9%]) of HIV-1 subtype B most likely originated from an Argentine strain, transferred through Liaoning infected individuals. In-depth analyses of 195 Shanghai subtype B sequences revealed that a total of 37.9% (n = 74) sequences contributed to 35 transmission networks, whereof 33.8% (n = 25) of the sequences associated with infected individuals from other provinces.Conclusions: Our new findings reflect the evolution complexity and transmission dynamics of HIV-1 subtype B in Shanghai, which would provide critical information for the design of effective prevention measures against HIV transmission. (C) 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.