Defining HIV-1 transmission clusters based on sequence data

Hassan, Amin S.; Pybus, Oliver G.; Sanders, Eduard J.; Albert, Jan; Esbjörnsson, Joakim

doi:10.1097/qad.0000000000001470

Cited by 136 publications

(150 citation statements)

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“…In comparison, we analysed 1442 HIV-1 pol sequences (approximately 1000 bp long) collected throughout Nigeria between 1999 and 2013 using maximum-likelihood and Bayesian phylogenetics. Importantly, the HIV-1 pol gene (which is the most targeted genetic region for HIV-1 sequencing and by far most commonly analysed region in studies of HIV-1 molecular epidemiology) holds sufficient intrinsic genetic variability to permit the reconstruction of transmission histories by phylogenetic approaches 26,32,61 . Hence, the larger size of our dataset, the relatively long time-window of sampling, and the use of state-of-the-art phylodynamic methods enabled us to perform the first in-depth nationwide HIV-1 phylodynamic study in Nigeria.…”

Section: Discussionmentioning

confidence: 99%

Characterisation of HIV-1 Molecular Epidemiology in Nigeria: Origin, Diversity, Demography and Geographic Spread

Nazziwa

Faria

Chaplin

et al. 2020

Sci Rep

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Nigeria has the highest number of AIDS-related deaths in the world. In this study, we characterised the HIV-1 molecular epidemiology by analysing 1442 HIV-1 pol sequences collected 1999-2014 from four geopolitical zones in Nigeria using state-of-the-art maximum-likelihood and Bayesian phylogenetic analyses. The main circulating forms were the circulating recombinant form (CRF) 02_AG (44% of the analysed sequences), CRF43_02G (16%), and subtype G (8%). Twenty-three percent of the sequences represented unique recombinant forms (URFs), whereof 37 (11%) could be grouped into seven potentially novel CRFs. Bayesian phylodynamic analysis suggested that five major Nigerian HIV-1 subepidemics were introduced in the 1960s and 1970s, close to the Nigerian Civil War. The analysis also indicated that the number of effective infections decreased in Nigeria after the introduction of free antiretroviral treatment in 2006. Finally, Bayesian phylogeographic analysis suggested gravity-like dynamics in which virus lineages first emerge and expand within large urban centers such as Abuja and Lagos, before migrating towards smaller rural areas. This study provides novel insight into the Nigerian HIV-1 epidemic and may have implications for future HIV-1 prevention strategies in Nigeria and other severely affected countries.

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Section: Discussionmentioning

confidence: 99%

Characterisation of HIV-1 Molecular Epidemiology in Nigeria: Origin, Diversity, Demography and Geographic Spread

Nazziwa

Faria

Chaplin

et al. 2020

Sci Rep

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“…Clusters identified by PhyCLIP should not be interpreted as sequences linked by rapid direct 645 transmission events. Transmission dynamic studies aim to integrate epidemiological clustering with 646 phylogenetic clusters to study transmission chains or local outbreak networks by assuming putative 647 transmission links between highly related sequences (Hassan et al 2017). Datasets from transmission 648 dynamic studies are likely to be sampled from localised outbreaks over a very specific period of time.…”

Section: Representative 644mentioning

confidence: 99%

Phylogenetic Clustering by Linear Integer Programming (PhyCLIP)

Han

Parker

Scholer

et al. 2018

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249/250 words)20 Sub-species nomenclature systems of pathogens are increasingly based on sequence data. The use of 21 phylogenetics to identify and differentiate between clusters of genetically similar pathogens is 22 particularly prevalent in virology from the nomenclature of human papillomaviruses to highly pathogenic 23 avian influenza (HPAI) H5Nx viruses. These nomenclature systems rely on absolute genetic distance 24 thresholds to define the maximum genetic divergence tolerated between viruses designated as closely 25 related. However, the phylogenetic clustering methods used in these nomenclature systems are limited 26 by the arbitrariness of setting intra-and inter-cluster diversity thresholds. The lack of a consensus 27 ground truth to define well-delineated, meaningful phylogenetic subpopulations amplifies the difficulties 28 in identifying an informative distance threshold. Consequently, phylogenetic clustering often becomes 29 an exploratory, ad-hoc exercise. 30Phylogenetic Clustering by Linear Integer Programming (PhyCLIP) was developed to provide a 31 statistically-principled phylogenetic clustering framework that negates the need for an arbitrarily-defined 32 distance threshold. Using the pairwise patristic distance distributions of an input phylogeny, PhyCLIP 33 parameterises the intra-and inter-cluster divergence limits as statistical bounds in an integer linear 34 programming model which is subsequently optimised to cluster as many sequences as possible. When 35 applied to the haemagglutinin phylogeny of HPAI H5Nx viruses, PhyCLIP was not only able to 36 recapitulate the current WHO/OIE/FAO H5 nomenclature system but also further delineated informative 37 higher resolution clusters that capture geographically-distinct subpopulations of viruses. PhyCLIP is 38 pathogen-agnostic and can be generalised to a wide variety of research questions concerning the 39 identification of biologically informative clusters in pathogen phylogenies. PhyCLIP is freely available at 40

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“…Viral populations may contain a pool of different variants that are resistant to different antiretroviral drugs 12,13 and also help the virus to evade the immune system 14 . Reconstructing the haplotypes present in a viral sample and assessing their phylodynamics may show additional or different transmission clusters present between individuals or identify a few HIV-1 strains that are dominating the HIV-1 viral population [15][16][17] . The use of powerful NGS technologies to study the HIV-1 epidemic at local levels (e.g., Washington, DC) may generate deeper insights into the ongoing HIV-1 dynamics.…”

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“…Towards this general aim, we 1) estimate the diversity of HIV-1 in Washington, DC, 2) determine the circulating drug resistant mutations, 3) identify and evaluate potential transmission clusters with consensus sequences and their association with epidemiologic and clinical factors, and 4) predict HIV-1 haplotypes for each sample and assess their potential for detecting transmission clusters. The number and size of transmission clusters may vary across HIV-1 gene regions 12,15,[23][24][25] , hence in this study we also compared phylodynamic inferences based on the polymerase and envelope HIV-1 genes.…”

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A cross-sectional study to characterize local HIV-1 dynamics in Washington, DC using next-generation sequencing

Gibson

Jair

Castel

et al. 2020

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the DC Cohort Executive Committee † Washington, DC continues to experience a generalized HIV-1 epidemic. We characterized the local phylodynamics of HIV-1 in DC using next-generation sequencing (NGS) data. Viral samples from 68 participants from 2016 through 2017 were sequenced and paired with epidemiological data. Phylogenetic and network inferences, drug resistant mutations (DRMs), subtypes and HIV-1 diversity estimations were completed. Haplotypes were reconstructed to infer transmission clusters. Phylodynamic inferences based on the HIV-1 polymerase (pol) and envelope genes (env) were compared. Higher HIV-1 diversity (n.s.) was seen in men who have sex with men, heterosexual, and male participants in DC. 54.0% of the participants contained at least one DRM. The 40-49 year-olds showed the highest prevalence of DRMs (22.9%). Phylogenetic analysis of pol and env sequences grouped 31.9-33.8% of the participants into clusters. HIV-TRACE grouped 2.9-12.8% of participants when using consensus sequences and 9.0-64.2% when using haplotypes. NGS allowed us to characterize the local phylodynamics of HIV-1 in DC more broadly and accurately, given a better representation of its diversity and dynamics. Reconstructed haplotypes provided novel and deeper phylodynamic insights, which led to networks linking a higher number of participants. Our understanding of the HIV-1 epidemic was expanded with the powerful coupling of HIV-1 NGS data with epidemiological data.Despite recent reductions in HIV-1 prevalence in Washington, DC from 2.5% in 2013 1 to 1.8% in 2018, the United States (US) capital is still experiencing a generalized HIV-1 epidemic -as defined by the World Health Organization 2-4 . There were 340 newly diagnosed cases in DC in 2018, and the DC rate is five times higher than the national rate 3 . Blacks, men, men who have sex with men (MSM), and heterosexuals (HRH) account for the majority of people living with HIV-1 (PLWH) in DC 2,3 . However, ~20% of the newly diagnosed persons had an unknown risk for transmission in both 2016 and 2017 2,3 . Furthermore, the leading group (33.3%) of newly diagnosed cases was between the ages of 20-29 years old 3 . This same age group had the highest percentage (27.5%) of drug resistance mutations (DRM) at diagnosis, suggesting broader spread of HIV-1 drug resistant variants and potential concern for future therapeutic options, especially if these mutations are against first line antiretroviral (ART) drugs for newly infected individuals. With blacks and young adults being the most impacted groups of individuals for HIV-1 in DC, understanding the current HIV-1 phylodynamics can provide informative data to guide programs that prevent and reduce the incidence of HIV-1. Moreover, identifying potential transmission clusters amongst individuals in DC and their associated epidemiological features may help infer otherwise 'unknown' transmission modes and provide insight for more targeted prevention and intervention strategies.In 2011, the DC Cohort, a longitudinal observational NIH-funded co...

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Defining HIV-1 transmission clusters based on sequence data

Cited by 136 publications

References 158 publications

Characterisation of HIV-1 Molecular Epidemiology in Nigeria: Origin, Diversity, Demography and Geographic Spread

Characterisation of HIV-1 Molecular Epidemiology in Nigeria: Origin, Diversity, Demography and Geographic Spread

Phylogenetic Clustering by Linear Integer Programming (PhyCLIP)

A cross-sectional study to characterize local HIV-1 dynamics in Washington, DC using next-generation sequencing

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