Molecular Transmission Networks Research Articles

Molecular transmission network and drug resistance in treatment-naïve HIV-1 infected patients in the Liangshan District, China.

Objective This study aimed to investigate the molecular transmission network and drug resistance in treatment-naïve HIV-1 infected patients in the Liangshan District, China. Methods The research subjects for this study were HIV-1 infected patients who did not receive any anti-retroviral therapy (ART) in the Liangshan District between January 2022 and July 2023. Peripheral venous whole blood samples were collected from the research subjects. 2 mL blood was used for CD4+ T lymphocyte counting detection. 10 mL blood was centrifuged to separate the plasma and blood cells for quantitative detection of HIV-1 RNA and DNA and drug resistance testing of HIV-1. Results A total of 156 participants were included in this study (88 males and 68 females). The median age of the participants was 37 years old. The findings revealed a positive correlation between the HIV-1 DNA and the HIV-1 RNA levels (r=0.478, P<0.001). However, a negative correlation was observed between HIV-1 DNA levels and CD4+ T lymphocyte counts (r=-0.186, P=0.020). Of the 156 participants, 148 were successfully tested for drug resistance of HIV-1 RNA and HIV-1 DNA simultaneously. Four cases failed the HIV-1 RNA drug resistance testing, and another four failed the HIV-1 DNA drug resistance testing. The most common HIV-1 subtype was the CRF07_BC recombinant. In this study, the overall incidence of transmitted drug resistance (TDR) was 8.33%. The resistance rates of non-nucleoside reverse transcriptase inhibitor (NNRTI) and protease inhibitor (PI) were 7.69% and 0.64%, respectively. Additionally, 32 participants were found to have drug-resistant mutations. The primary drug-resistant mutations were K103N, V179D, E157Q, and A128T, mainly against efavirenz (EFV) and nevirapine (NVP) resistance. Conclusion The drug resistance of HIV-1 infected ART-naïve patients in the Liangshan District cannot be ignored. HIV-1 drug resistance testing is recommended before initiating ART.

Epidemic characteristics of local HIV-2 transmission across Hunan province, China

ObjectiveTo elucidate the epidemiological features of HIV-2 in Hunan Province, China, utilizing sequence analysis. MethodsThirteen individuals diagnosed with HIV-2 infection in Hunan Province, China, from 2017 to 2023 were included in this study. Amplification of HIV-2 env and pol regions was conducted, followed by Sanger sequencing. Phylogenetic and molecular transmission network analyses were performed to delineate molecular features and transmission dynamics. ResultsAll 14 individuals contracted HIV-2 through heterosexual intercourse, comprising 7 males and 7 females, with a median age of 58 years. Among them, three couples (HN001 and HN013, HN010 and HN011, HN008 and HN009) were identified, along with commercial sexual activity engagement reported for subject HN004. Notably, subjects HN001, HN003, HN008, and HN010 engaged in commercial sexual activities at the same location as subject HN004. Phylogenetic analysis of the pol gene revealed close proximity of sequences from all subjects to reference sequences from Gambia (Sub-type A). Employing a genetic distance threshold of 1.5 %, eight out of the 14 subjects formed a molecular transmission network, with HN002 and HN004 identified as central nodes. ConclusionFrom 2017 to 2023, all HIV-2-infected individuals in Hunan Province, China, acquired the virus through identifiable routes, indicating transmission of similar HIV-2 strains among them.

Hepatitis C virus subtype diversity and transmission clusters characteristics among drug users in Zhuhai, South China

BackgroundHepatitis C virus (HCV) infection poses a major public health challenge globally, especially among injecting drug users. China has the world’s largest burden of HCV infections. However, little is known about the characteristics of transmission networks among drug user populations. This study aims to investigate the molecular epidemiology and transmission characteristics of HCV infections among drug users in Zhuhai, a bustling port city connecting Mainland China and its Special Administrative Regions.MethodsParticipants enrolled in this study were drug users incarcerated at Zhuhai’s drug rehabilitation center in 2015. Their sociodemographic and behavioral information, including gender, promiscuity, drug use method, and so forth, was collected using a standardized questionnaire. Plasmas separated from venous blood were analyzed for HCV infection through ELISA and RT-PCR methods to detect anti-HCV antibodies and HCV RNA. The 5’UTR fragment of the HCV genome was amplified and further sequenced for subtype identifications and phylogenetic analysis. The phylogenetic tree was inferred using the Maximum Likelihood method based on the Tamura-Nei model, and the transmission cluster network was constructed using Cytoscape3.8.0 software with a threshold of 0.015. Binary logistic regression models were employed to assess the factors associated with HCV infection.ResultsThe overall prevalence of HCV infection among drug users was 44.37%, with approximately 19.69% appearing to clear the HCV virus successfully. Binary logistic regression analysis revealed that those aged over 40, engaging in injecting drug use, and being native residents were at heightened risk for HCV infection among drug user cohorts. The predominant HCV subtypes circulating among those drug users were 6a (60.26%), followed by 3b (16.7%), 3a (12.8%), 1b (6.41%) and 1a (3.85%), respectively. Molecular transmission network analysis unveiled the presence of six transmission clusters, with the largest propagation cluster consisting of 41 individuals infected with HCV subtype 6a. Furthermore, distinct transmission clusters involved eight individuals infected with subtype 3b and seven with subtype 3a were also observed.ConclusionThe genetic transmission networks revealed a complex transmission pattern among drug users in Zhuhai, emphasizing the imperative for a targeted and effective intervention strategy to mitigate HCV dissemination. These insights are pivotal for shaping future national policies on HCV screening, treatment, and prevention in port cities.

Exploring HIV-1 transmission features among older individuals in developed eastern China.

The number of newly reported HIV-1 infections among older individuals (aged ≥50 years) has increased rapidly in Hangzhou, a central city in the Yangtze River Delta region of China. To provide a scientific basis for prevention and intervention strategies targeted at older individuals in Hangzhou, an epidemiological survey combined with molecular transmission network analysis was conducted. A total of 2899 individuals with newly confirmed HIV-1 infections, including 635 older individuals and 2264 younger individuals (aged <50 years), were enrolled in this study. Among older individuals, heterosexual contact was the predominant mode of HIV-1 transmission. Additionally, it was observed that older individuals with lower levels of education exhibited a higher susceptibility to HIV-1 infection. The analysis of transmission network which was inferred using HIV-TRACE algorithm revealed that the newly diagnosed HIV-1 infections among older individuals in Hangzhou exhibited a pattern of scattered transmission, with key clusters primarily located in non-main urban areas. The predominant mode of transmission in these areas was non-marital and non-commercial or non-marital and commercial heterosexual transmission. Notably, the study highlighted a significant proportion of older individuals (73.3%, 11/15) within B subtype. Multivariate logistic regression analysis further revealed that the subtype B was a significant factor associated with older individuals having ≥3 node degrees in the network, occurring 5.55 times more frequent than subtype CRF07_BC (95% CI = 1.17-26.22, p = 0.031). Furthermore, the lower CD4 levels observed among older individuals underscored the challenge of late diagnosis in Hangzhou. Taken together, it is imperative to test and intervene for high-risk older individuals. To tackle this issue effectively, it is essential to enhance the detection of the B subtype and implement targeted interventions in key clusters within non-main urban areas. Additionally, proactive measures should be implemented to address the challenge of late diagnosis in Hangzhou by promoting widespread testing among the older individuals, particularly in priority areas.

Distribution pattern, molecular transmission networks, and phylodynamic of hepatitis C virus in China.

In China, few molecular epidemiological data on hepatitis C virus (HCV) are available and all previous studies were limited by small sample sizes or specific population characteristics. Here, we report characterization of the epidemic history and transmission dynamics of HCV strains in China. We included HCV sequences of individuals belonging to three HCV surveillance programs: 1) patients diagnosed with HIV infection at the Beijing HIV laboratory network, most of whom were people who inject drugs and former paid blood donors, 2) men who have sex with men, and 3) the general population. We also used publicly available HCV sequences sampled in China in our study. In total, we obtained 1,603 Ns5b and 865 C/E2 sequences from 1,811 individuals. The most common HCV strains were subtypes 1b (29.1%), 3b (25.5%) and 3a (15.1%). In transmission network analysis, factors independently associated with clustering included the region (OR: 0.37, 95% CI: 0.19-0.71), infection subtype (OR: 0.23, 95% CI: 0.1-0.52), and sampling period (OR: 0.43, 95% CI: 0.27-0.68). The history of the major HCV subtypes was complex, which coincided with some important sociomedical events in China. Of note, five of eight HCV subtype (1a, 1b, 2a, 3a, and 3b), which constituted 81.8% HCV strains genotyped in our study, showed a tendency towards decline in the effective population size during the past decade until present, which is a good omen for the goal of eliminating HCV by 2030 in China.

Epidemiological characteristics of HIV transmission in southeastern China from 2015 to 2020 based on HIV molecular network.

HIV/AIDS remains a global public health problem, and understanding the structure of social networks of people living with HIV/AIDS is of great importance to unravel HIV transmission, propose precision control and reduce new infections. This study aimed to investigate the epidemiological characteristics of HIV transmission in Fujian province, southeastern China from 2015 to 2020 based on HIV molecular network. Newly diagnosed, treatment-naive HIV/AIDS patients were randomly sampled from Fujian province in 2015 and 2020. Plasma was sampled for in-house genotyping resistance test, and HIV molecular network was created using the HIV-TRACE tool. Factors affecting the inclusion of variables in the HIV molecular network were identified using univariate and multivariate logistic regression analyses. A total of 1,714 eligible cases were finally recruited, including 806 cases in 2015 and 908 cases in 2020. The dominant HIV subtypes were CRF01_AE (41.7%) and CRF07_BC (38.3%) in 2015 and CRF07_BC (53. 3%) and CRF01_AE (29.1%) in 2020, and the prevalence of HIV drug resistance was 4.2% in 2015 and 5.3% in 2020. Sequences of CRF07_BC formed the largest HIV-1 transmission cluster at a genetic distance threshold of both 1.5 and 0.5%. Univariate and multivariate logistic regression analyses showed that ages of under 20 years and over 60 years, CRF07_BC subtype, Han ethnicity, sampling in 2015, absence of HIV drug resistance, married with spouse, sampling from three cities of Jinjiang, Nanping and Quanzhou resulted in higher proportions of sequences included in the HIV transmission molecular network at a genetic distance threshold of 1.5% (p < 0.05). Our findings unravel the HIV molecular transmission network of newly diagnosed HIV/AIDS patients in Fujian province, southeastern China, which facilitates the understanding of HIV transmission patterns in the province.

Using the Molecular Transmission Networks to Analyze the Epidemic Characteristics of HIV-1 CRF08_BC in Kunming, Yunnan.

HIV-1CRF08_BC is the most prevalent epidemic subtype among heterosexual (HET) and intravenous drug users (IDUs) in Kunming, Yunnan. Using the pol region of gene sequences derived from molecular epidemiological surveys, we developed a molecular transmission network for the purpose of analyzing its epidemiological characteristics, assessing its epidemiological trends, identifying its potential transmission relationships, and developing targeted interventions. HyPhy 2.2.4 was used to calculate pairwise genetic distances between sequences; GraphPad-Prism 8.0 was employed to determine the standard genetic distance; and Cytoscope 3.7.2 was applied to visualize the network. We used the network analysis tools to investigate network characteristics and the Molecular Complex Detection (MCODE) tool to observe the growth of the network. We utilized a logistic regression model to examine the factors influencing clustering and a zero-inflated Poisson model to investigate the factors influencing potential transmission links. At the standard genetic distance threshold of 0.008, 406 out of 858 study participants were clustered in 132 dissemination networks with a total network linkage of 868, and the number of links per sequence ranged from 1 to 19. The MCODE analysis identified three significant modular clusters in the networks, with network scores ranging from 4.9 to 7. In models of logistic regression, HET, middle-aged and elderly individuals, and residents of northern and southeastern Kunming were more likely to enter the transmission network. According to the zero-inflated Poisson model, age, transmission category, sampling year, marital status, and CD4+ T level had a significant effect on the size of links. The molecular clusters in Kunming's molecular transmission network are specific and aggregate to a certain extent. HIV-1 molecular network analysis provided information on local transmission characteristics, and these findings helped to determine the priority of transmission-reduction interventions.

Prevention and Control Are Not a Regional Matter: A Spatial Correlation and Molecular Linkage Analysis Based on Newly Reported HIV/AIDS Patients in 2021 in Jiangsu, China.

HIV-related spatial analysis studies in China are relatively few, and Jiangsu Province has not reported the relevant data in recent years. To describe the spatial distribution and molecular linkage characteristics of HIV-infected patients, this article combined descriptive epidemiology, spatial analysis, and molecular epidemiology methods to analyze patient reporting, patient mobility information, and HIV sequence information simultaneously. The results showed that HIV reporting profiles differed among Jiangsu cities, with the reporting rate in southern Jiangsu being above average. There was a spatial autocorrelation (Global Moran I = 0.5426, p < 0.05), with Chang Zhou showing a High-High aggregation pattern. Chang Zhou and Wu Xi were identified as hotspots for HIV reporting and access to molecular transmission networks. Some infected individuals still showed cross-city or even cross-province mobility after diagnosis, and three were linked with individuals in the destination cities within the largest molecular transmission cluster, involving 196 patients. The cross-city or cross-province mobility of patients may result in a potential HIV transmission risk, suggesting that combining timely social network surveys, building an extensive transmission network across cities and provinces, and taking critical regions and key populations as entry points could contribute to improved prevention and control efficiency and promote achievement of the 95-95-95 target and cascade.

HIV-1 molecular transmission network and drug resistance in Chongqing, China, among men who have sex with men (2018–2021)

BackgroundOver the past few years, HIV transmission among men who have sex with men (MSM) in China has increased significantly. Chongqing, located in the southwest of China, has the highest prevalence of HIV among MSM in the country.MethodsBlood samples were taken from 894 MSM in Chongqing who had recently been diagnosed with HIV-1 infection and had not yet started getting treatment. In order to determine the distribution of HIV-1 subtypes, transmitted drug resistance, and assessments of molecularly transmitted clusters, we sequenced the Pol genes and employed them in phylogenetic analysis. The genetic distance between molecular clusters was 1.5%. To find potential contributing factors, logistic regression analyses were performed.ResultsOf the 894 HIV-1 pol sequences acquired from study participants, we discovered that CRF07_BC (73.6%) and CRF01_AE (19.6%) were the two most prevalent HIV-1 genotypes in Chongqing among MSM, accounting for 93.2% of all infections. In addition, CRF08_BC (1.1%), B subtype (1.0%), CRF55_01B (3.4%), and URF/Other subtypes (1.3%) were less frequently observed. Among MSM in Chongqing, transmitted drug resistance (TDR) was reported to be present at a rate of 5.6%. 48 clusters with 600 (67.1%, 600/894) sequences were found by analysis of the molecular transmission network. The distributions of people by age, sexual orientation, syphilis, and genotype were significantly differentially related to being in clusters, according to the multivariable logistic regression model.ConclusionDespite the low overall prevalence of TDR, the significance of genotypic drug resistance monitoring needs to be emphasized. CRF07_BC and CRF01_AE were the two main genotypes that created intricate molecular transmission networks. In order to prevent the expansion of molecular networks and stop the virus’s spread among MSM in Chongqing, more effective HIV intervention plans should be introduced.

Characteristics of genotype, drug resistance, and molecular transmission network among newly diagnosed HIV-1 infections in Shenzhen, China.

The HIV-1 pandemic has persisted for four decades, and poses a major challenge to global public health. Shenzhen, a city with large number of migrant populations in China, is suffering HIV-1 epidemic. It is necessary to continuously conduct the molecular surveillance among newly diagnosed HIV-1 patients in these migrant population. In this study, plasma samples of newly diagnosed and ART-naive HIV-1 infections were collected from Shenzhen city in China. The partial genes of HIV-1 gag and pol were amplified and sequenced for the analysis of genotype, drug resistance, and molecular transmission network. Ninety-one sequences of pol gene were obtained from newly diagnosed HIV-1 infections in Shenzhen, and seven HIV-1 subtypes were revealed in this investigation. Among them, the circulating recombinant form (CRF) 07_BC was the mostly frequent subtype (53.8%, 49/91), followed by CRF01_AE (20.9%, 19/91), CRF55_01B (9.9%, 9/91), unique recombinant forms (URFs) (8.8%, 8/91), B (3.3%, 3/91), CRF59_01B (2.2%, 2/91), and CRF08_BC (1.1%, 1/91). The overall prevalence of pretreatment drug resistance (PDR) was 23.1% (21/91), and 52.38% (11/21) of the PDR was specific for the nonnucleotide reverse transcriptase inhibitors (NNRTIs). Furthermore, a total of 3091 pol gene sequences were used to generate 19 molecular transmission clusters, and then one growing cluster, a new cluster, and a cluster with growth reactivation were identified. The result revealed that more sexual partner, CRF_07BC subtype, and seven amino acid deletions in gag p6 region might be the influencing factors associated with the high risk of transmission behavior. Compared with CRF01_AE subtype, CRF07_BC subtype strains were more likely to form clusters in molecular transmission network. This suggests that long-term surveillance of the HIV-1 molecular transmission should be a critical measure to achieve a precise intervention for controlling the spread of HIV-1 in China.

Network typologies predict future molecular linkages in the network of HIV transmission in Florida.

HIV molecular transmission network typologies have previously demonstrated associations to transmission risk; however, few studies have evaluated their predictive potential in anticipating future transmission events. To assess this, we tested multiple models on statewide surveillance data from the Florida Department of Health. This was a retrospective, observational cohort study examining the incidence of new HIV molecular linkages within the existing molecular network of persons with HIV (PWH) in Florida. HIV-1 molecular transmission clusters were reconstructed for PWH diagnosed in Florida from 2006-2017 using the HIV-TRAnsmission Cluster Engine (HIV-TRACE). A suite of machine-learning models designed to predict linkage to a new diagnosis were internally and temporally externally validated using a variety of demographic, clinical, and network-derived parameters. Of the 9,897 individuals who received a genotype within 12 months of diagnosis during 2012-2017, 2,611 (26.4%) were molecularly linked to another case within 1 year at 1.5% genetic distance. The best performing model, trained on two years of data, was high performing (area under the receiving operating curve = 0.96, sensitivity = 0.91, and specificity = 0.90) and included the following variables: age group, exposure group, node degree, betweenness, transitivity, and neighborhood. In the molecular network of HIV transmission in Florida, individuals' network position and connectivity predicted future molecular linkages. Machine-learned models using network typologies performed superior to models using individual data alone. These models can be used to more precisely identify subpopulations for intervention.

Increased prevalence and stable clustering rate of HIV-1 transmitted drug resistance strains after 'treat-all' in a megacity of China.

The 'treat-all' strategy was implemented in Shenzhen, China in 2016. The effect of this extensive treatment on transmitted drug resistance (TDR) of HIV is unclear. TDR analysis was performed, based on the partial HIV-1 pol gene obtained from the newly reported HIV-1 positive cases from 2011 to 2019 in Shenzhen, China. The HIV-1 molecular transmission networks were inferred to analyse the spread of TDR. Logistic regression was used to identify the potential risk factors with TDR mutations (TDRMs) to cluster. A total of 12 320 partial pol sequences were included in this study. The prevalence of TDR was 2.95% (363/12 320), which increased from 2.57% to 3.52% after 'treat-all'. The TDR prevalence was increased in populations with the characteristics of CRF07_BC, being single, educated to junior college level and above, MSM and male. The sensitivities of viruses to six antiretroviral drugs were decreased. The clustering rate of TDRMs remained stable, and the sequences in the three drug resistance transmission clusters (DRTCs) were mainly found during 2011-16. CRF07_BC and CRF55_01B were the factors associated with TDRMs clustering in the networks. The 'treat-all' strategy might have contributed to a small increase in TDR, while most of the TDRMs were distributed sporadically, which implies that the 'treat-all' strategy is helpful for the control of TDR in high-risk populations.

The characteristics of HIV-1 subtype B on phylogenetic dynamic and molecular transmission network in Fuyang City, China, 2011 to 2019.

HIV-1 subtype B, as once one of the earliest strains introduced into mainland China rapidly spread in commercial plasma donors and heterosexuals in 1990s. Here, we aim to investigate the origin and evolutionary history of HIV-1 subtype B in Fuyang city, China. We collected sequences tested from Fuyang in the east of China where higher prevalence of HIV-1 among commercial plasma donors and heterosexuals to construct a phylogenetic tree using the Markov chain Monte Carlo (MCMC) algorithm, infer molecular transmission network using TN93 model and visualize it with Cytoscape software. Our results showed that >99% of subtype B sequences belonged to Thai B. The sequences from Fuyang often cluster closer to those from other its adjacent cities, which clustered together and formed a monophyletic cluster. HIV-1 B circulating in Fuyang dates back to approximately 1990. Among the 1,437 sequences, 166 clustered at a genetic distance of ≤1.2%, resulting in 73 clusters. The degree of clustering with at least one other person was 11.55%. Among the transmission clusters, 50 (80.65%) comprised two individuals. Most clusters consisted of both heterosexual transmission routes and men who have sex with men. Phylogenetic and molecular network analyses revealed a common origin with neighboring regions in mainland China, local onwards transmission after its introduction, and a limited clustering degree. However, at least two co-existing transmission routes in most transmission clusters imply a greater challenge in controlling the spread of HIV-1. Our findings highlight the value on tailoring prevention interventions by combination of molecular surveillance and epidemiology.

Molecular Transmission Network of Newly Reported HIV Infections in Pengzhou, Sichuan Province: A Study Based on Genomics and Spatial Epidemiology.

The objective of this study was to understand the molecular transmission characteristics of newly reported HIV infections in the city of Pengzhou, Sichuan Province, to analyze the risk factors of transmission network and spatial clustering and the transmission characteristics, and to provide a scientific basis for precision prevention and intervention. Anticoagulated whole blood was collected from newly reported HIV infections in Pengzhou from March 2019 to August 2021. After the plasma was isolated, the HIV-1 pol gene was amplified and sequenced by reverse transcriptase polymerase chain reaction (PCR). The obtained gene sequences were used to construct a maximum likelihood phylogenetic tree for the analysis of virus subtypes, and a molecular transmission network was constructed using the genetic distance method to evaluate the transmission pattern of people living with HIV/AIDS in Pengzhou. A logistic regression model was used to find out the potential risk factors for entering the molecular transmission network with the number of nodes ≥ 2. Spatial analysis is used to show the geographical pattern of the proportion of newly reported HIV infections entering the molecular transmission network, and a flow map is used to show the intensity of transmission within and between townships. A total of 463 newly reported HIV-infection sequences were obtained in this study, including 237 cases (51.19%) of CRF01_ AE, 159 cases (34.34%) of CRF07_BC, 45 cases (9.72%) of B, 15 cases (3.24%) of CRF08_BC and 7 cases (1.5%) of others. The number of clusters was the highest when the gene distance was 0.009, with a total of 246 sequences entering the network, forming 54 clusters, and the network entry rate was 55.36%. There were 170 sequences with more than two nodes in the network sequence. The logistic regression showed that compared with age < 50 years old, age ≥ 50 years old has a higher risk of transmission (OR = 3.43, 95% CI = 2.06-5.71); compared with farmers, the risk of transmission within industry is lower (OR = 0.046, 95% CI = 0.25-0.87); and compared with CRF07_BC, CRF01_AE (OR = 6.09, 95% CI = 3.60-10.30) and B (OR = 20.31, 95% CI = 8.94-46.13) had a higher risk of transmission. Men aged ≥ 50 years are mainly clustered with women between 50 and 70 years of age. In addition to being clustered with gay men, there are nine (50%) and three (16.7%) chains of transmission between gay men and heterosexual men and women, respectively. In the geographical space, there is no hot spot clustering of the molecular propagation network. The subtype B was mainly distributed in the town of Tianpeng and formed transmission networks in eastern Pengzhou;0020CRF01_AE is mainly distributed in the town of Lichun and formed transmission networks in the west and north of Pengzhou. This study reveals the characteristics and influencing factors of molecular network transmission in the region, as well as the spatial transmission characteristics of newly reported HIV infections in recent years, and reveals the geographical differences in HIV-1 transmission. The results provide a scientific basis for the development of local AIDS-specific intervention measures.

Impact of molecular sequence data completeness on HIV cluster detection and a network science approach to enhance detection

Detection of viral transmission clusters using molecular epidemiology is critical to the response pillar of the Ending the HIV Epidemic initiative. Here, we studied whether inference with an incomplete dataset would influence the accuracy of the reconstructed molecular transmission network. We analyzed viral sequence data available from ~ 13,000 individuals with diagnosed HIV (2012–2019) from Houston Health Department surveillance data with 53% completeness (n = 6852 individuals with sequences). We extracted random subsamples and compared the resulting reconstructed networks versus the full-size network. Increasing simulated completeness was associated with an increase in the number of detected clusters. We also subsampled based on the network node influence in the transmission of the virus where we measured Expected Force (ExF) for each node in the network. We simulated the removal of nodes with the highest and then lowest ExF from the full dataset and discovered that 4.7% and 60% of priority clusters were detected respectively. These results highlight the non-uniform impact of capturing high influence nodes in identifying transmission clusters. Although increasing sequence reporting completeness is the way to fully detect HIV transmission patterns, reaching high completeness has remained challenging in the real world. Hence, we suggest taking a network science approach to enhance performance of molecular cluster detection, augmented by node influence information.

Molecular genetics and epidemiological characteristics of HIV-1 epidemic strains in various sexual risk behaviour groups in developed Eastern China, 2017–2020

ABSTRACT 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.

Molecular transmission network of pretreatment drug resistance among human immunodeficiency virus-positive individuals and the impact of virological failure on those who received antiretroviral therapy in China.

ObjectivesWe investigated the prevalence of pretreatment drug resistance (PDR), the molecular transmission network among HIV-positive individuals, and the impact of virological failure on those who received antiretroviral therapy (ART) in China.MethodsBased on the World Health Organization (WHO) surveillance guidelines for PDR, a baseline survey and follow-up were conducted in 2018 and 2021, respectively. Demographic information and plasma samples were obtained from all participants. HIV pol gene region sequences were used to analyze the PDR and molecular transmission networks using the Stanford HIV database algorithm and HIV-TRACE, respectively. This study assessed the odds ratios (OR) of PDR to virological failure (viral load ≥ 50 copies/mL) after 3 years of ART using multivariable logistic regression.ResultsOf the 4,084 individuals, 370 (9.1%) had PDR. The prevalence of PDR to non-nucleoside reverse transcriptase inhibitors (5.2%) was notably higher than that to nucleoside reverse transcriptase inhibitors (0.7%, p < 0.001), protease inhibitors (3.0%, p < 0.001), and multidrug resistance (0.3%, p < 0.001). A total of 1,339 (32.8%) individuals from 361 clusters were enrolled in the molecular transmission network. Of the 361 clusters, 22 included two or more individuals with PDR. The prevalence of virological failure among HIV-positive individuals after 3 years of ART without PDR, those with PDR to Chinese listed drugs, and those with PDR to other drugs was 7.9, 14.3, and 12.6%, respectively. Compared with that in HIV-positive individuals without PDR, virological failure after 3 years of ART was significantly higher (OR: 2.02, 95% confidence interval (CI): 1.25–3.27) and not significantly different (OR: 1.72, 95% CI: 0.87–3.43) in individuals with PDR to Chinese listed drugs and those with PDR to other drugs, respectively. Missed doses in the past month were significantly associated with virological failure (OR, 2.82; 95% CI: 4.08–5.89).ConclusionThe overall prevalence of PDR was close to a high level and had an impact on virological failure after 3 years of ART. Moreover, HIV drug-resistant strains were transmitted in the molecular transmission network. These results illustrate the importance of monitoring PDR and ensuring virological suppression through drug adherence.

Prospects for the Implementation of HIV Molecular Transmission Network–Informed AIDS Prevention and Control in China

Abstract The human immunodeficiency virus (HIV)–infected population with a transmission link has a strong genetic similarity in viral gene sequences that tend to cluster. In recent years, a strategy for guiding HIV/acquired immunodeficiency syndrome (AIDS) prevention using sequence-based transmission networks has been proposed. The execution of this strategy provides an opportunity to effectively control the spread of the AIDS epidemic in China. HIV molecular transmission network research has been actively pursued by a number of Chinese research groups. Medium- and long-term strategies were created with the goal of using HIV molecular transmission networks to guide targeted prevention and control in China. Technical guidelines for HIV transmission network monitoring and intervention have been written and released. Pilot studies are continuing in the meantime. Despite the fact that this strategy has a bright future, there are still many challenges to overcome to achieve the intended AIDS prevention and control goals.

Molecular Epidemiology of HIV-1 among Prisoners in Central Brazil and Evidence of Transmission Clusters.

Higher rates of human immunodeficiency virus (HIV) infection have been detected in prisoners when compared with the general population, but research into HIV molecular epidemiology and its transmission network has been lacking among them. Thus, this study aimed to verify potential HIV molecular transmission networks among prisoners. In addition, we aimed to describe the mutations related to antiretroviral resistance in these isolates. Thus, we conducted a cross-sectional survey from 2013 to 2018 in prisons in Central-Western Brazil, and the final sampling composed of 84 prisoners. Proviral DNA was extracted from each whole blood sample followed by amplification of the partial polymerase gene and sequencing. Forty-nine sequences (58.3%) were classified as subtype B, followed by C (14.3%), D, and F1 (2.4% each). A complex and dynamic HIV-1 epidemic is observed in the prisons, as 25% of the sequences were recombinant forms. We detected 15 HIV transmission clusters composed of at least two sequences, that included not only prisoners but also individuals from the general population from the same State with a variety of risk behaviors. Thirty-two percent (32.0%) of treatment-experienced prisoners had at least one drug resistance mutation (DRM), while transmitted DRMs were found in 5.9% of the prisoners. We highlight the urgent need for routine surveillance of HIV-1 infection including resistance genotypic tests considering the high disease burden, risky behaviors inside prisons, and the dynamic relationship of prisoners with the outside community.

Transmission networks of hepatitis C virus among HIV/HCV-coinfected patients in Guangdong, China

BackgroundCoinfection with hepatitis C virus (HCV) is common in human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients due to shared routes of transmission. We aimed to investigate the characteristics of HCV subgenotypes among HIV/HCV-coinfected patients in Guangdong and explore the molecular transmission networks and related risk factors for HCV strains.MethodsPlasma samples were obtained from 356 HIV/HCV-coinfected patients for HCV NS5B region sequencing. A neighbor-joining phylogenetic tree was constructed to affirm HCV subgenotypes. The transmission networks based on maximum likelihood phylogenetic tree were determined by Cluster Picker, and visualized using Cytoscape 3.2.1.ResultsA total of 302 HCV NS5B sequences were successfully amplified and sequenced from the 356 plasma samples. A neighbor-joining phylogenetic tree based on the 302 NS5B sequences revealed the profile of HCV subgenotypes circulating among HIV/HCV coinfection patients in Guangdong. Two predominant strains were found to be 6a (58.28%, 176/302) and 1b (18.54%, 56/302), followed by 3a (10.93%, 33/302), 3b (6.95%, 21/302), 1a (3.64%, 11/302), 2a (0.99%, 3/302) and 6n (0.66%, 2/302). A molecular transmission network of five major HCV genotypes was constructed, with a clustering rate of 44.04%. The clustering rates of subgenotypes 1a, 3a, 3b, 1b, and 6a were 18.18% (2/11), 42.42%, 52.38%, 48.21%, and 44.89%, respectively. Multivariate logistic regression analysis showed no significant effects from sex, age, transmission route, geographical region, baseline CD4 + T cell count or subgenotype (P > 0.05), except marital status. Married or cohabiting people (compared with unmarried people) had more difficulty forming transmission networks.ConclusionsIn summary, this study, based on HCV NS5B subgenotypes, revealed the HCV subtype diversity and distribution among HIV/HCV-coinfected patients in Guangdong. Marital status inclined to be the factor influencing HCV transmission networks formation.