Dataset Information

Phylogenetic prioritization of HIV-1 transmission clusters with viral lineage-level diversification rates.

ABSTRACT:

Background and objectives

Public health officials faced with a large number of transmission clusters require a rapid, scalable and unbiased way to prioritize distribution of limited resources to maximize benefits. We hypothesize that transmission cluster prioritization based on phylogenetically derived lineage-level diversification rates will perform as well as or better than commonly used growth-based prioritization measures, without need for historical data or subjective interpretation.

Methodology

9822 HIV pol sequences collected during routine drug resistance genotyping were used alongside simulated sequence data to infer sets of phylogenetic transmission clusters via patristic distance threshold. Prioritized clusters inferred from empirical data were compared to those prioritized by the current public health protocols. Prioritization of simulated clusters was evaluated based on correlation of a given prioritization measure with future cluster growth, as well as the number of direct downstream transmissions from cluster members.

Results

Empirical data suggest diversification rate-based measures perform comparably to growth-based measures in recreating public heath prioritization choices. However, unbiased simulated data reveals phylogenetic diversification rate-based measures perform better in predicting future cluster growth relative to growth-based measures, particularly long-term growth. Diversification rate-based measures also display advantages over growth-based measures in highlighting groups with greater future transmission events compared to random groups of the same size. Furthermore, diversification rate measures were notably more robust to effects of decreased sampling proportion.

Conclusions and implications

Our findings indicate diversification rate-based measures frequently outperform growth-based measures in predicting future cluster growth and offer several additional advantages beneficial to optimizing the public health prioritization process.

SUBMITTER: Miller RL

PROVIDER: S-EPMC9311310 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background and objectivesAlthough HIV sequence clustering is routinely used to identify subpopulations experiencing elevated transmission, it over-simplifies transmission dynamics and is sensitive to methodology. Complementarily, viral diversification rates can be used to approximate historical transmission rates. Here, we investigated the concordance and sensitivity of HIV transmission risk factors identified by phylogenetic clustering, viral diversification rate, changes in viral diversification rate and a combined approach.MethodologyViral sequences from 9848 people living with HIV in British Columbia, Canada, sampled between 1996 and February 2019, were used to infer phylogenetic trees, from which clusters were identified and viral diversification rates of each tip were calculated. Factors associated with heightened transmission risk were compared across models of cluster membership, viral diversification rate, changes in diversification rate, and viral diversification rate among clusters.ResultsViruses within larger clusters had higher diversification rates and lower changes in diversification rate than those within smaller clusters; however, rates within individual clusters, independent of size, varied widely. Risk factors for both cluster membership and elevated viral diversification rate included being male, young, a resident of health authority E, previous injection drug use, previous hepatitis C virus infection or a high recent viral load. In a sensitivity analysis, models based on cluster membership had wider confidence intervals and lower concordance of significant effects than viral diversification rate for lower sampling rates.Conclusions and implicationsViral diversification rate complements phylogenetic clustering, offering a means of evaluating transmission dynamics to guide provision of treatment and prevention services.Lay summaryUnderstanding HIV transmission dynamics within clusters can help prioritize public health resource allocation. We compared socio-demographic and clinical risk factors associated with phylogenetic cluster membership and viral diversification rate, a historical branching rate, in order to assess their relative concordance and sampling sensitivity.

Project description:BackgroundTransmission patterns of sexually-transmitted infections (STIs) could relate to the structure of the underlying sexual contact network, whose features are therefore of interest to clinicians. Conventionally, we represent sexual contacts in a population with a graph, that can reveal the existence of communities. Phylogenetic methods help infer the history of an epidemic and incidentally, may help detecting communities. In particular, phylogenetic analyses of HIV-1 epidemics among men who have sex with men (MSM) have revealed the existence of large transmission clusters, possibly resulting from within-community transmissions. Past studies have explored the association between contact networks and phylogenies, including transmission clusters, producing conflicting conclusions about whether network features significantly affect observed transmission history. As far as we know however, none of them thoroughly investigated the role of communities, defined with respect to the network graph, in the observation of clusters.MethodsThe present study investigates, through simulations, community detection from phylogenies. We simulate a large number of epidemics over both unweighted and weighted, undirected random interconnected-islands networks, with islands corresponding to communities. We use weighting to modulate distance between islands. We translate each epidemic into a phylogeny, that lets us partition our samples of infected subjects into transmission clusters, based on several common definitions from the literature. We measure similarity between subjects' island membership indices and transmission cluster membership indices with the adjusted Rand index.Results and conclusionAnalyses reveal modest mean correspondence between communities in graphs and phylogenetic transmission clusters. We conclude that common methods often have limited success in detecting contact network communities from phylogenies. The rarely-fulfilled requirement that network communities correspond to clades in the phylogeny is their main drawback. Understanding the link between transmission clusters and communities in sexual contact networks could help inform policymaking to curb HIV incidence in MSMs.

Project description:BackgroundPublic health measures designed to reduce SARS-CoV-2 transmission led to reduced access to care and prevention services for people living with or at risk of acquiring HIV, particularly during the initial introduction of extensive restrictions. This reduction in access may have contributed to increases in HIV transmission not outweighed by decreases in transmission occurring as a result of reduced contact rates promoted by the same public health measures.MethodsWe synthesize available province-wide HIV data in British Columbia, Canada, together with public mobility data to phylogenetically investigate the early impacts of SARS-CoV-2 on HIV transmission. Cluster growth, coalescent branching events and lineage-level diversification rates were assessed in "pre-lockdown" (January 22-March 21, 2020), "lockdown" (March 22-May 20, 2020) and "post-lockdown" (May 21-July 19, 2020) to facilitate comparison of transmission trends across key populations.FindingsResults reveal increased HIV transmission in a limited number of clusters in association with reduced access to health services during the initial introduction of SARS-CoV-2-related restrictions. In particular, clusters associated with people who inject drugs (PWID) show rapid growth, extensive branching events in phylogenetic trees during and following the lockdown period, and elevated median change in individuals' viral diversification rates during lockdown compared to clusters associated with men who have sex with men (MSM), consistent with increased transmission rates between PWID.InterpretationIncreased vigilance and innovative targeted solutions are critical to offset potential negative impacts of SARS-CoV-2 or future pandemic-related restrictions on HIV epidemic dynamics.FundingFunding sources include Genome Canada and Genome BC, the Public Health Agency of Canada, the BC Centre for Excellence in HIV/AIDS, and the Canadian Institutes of Health Research Coronavirus Rapid Response Programme. Student funding includes a NSERC CREATE scholarship and a Canadian Institutes of Health Research graduate fellowship.