Phylogenetic studies of transmission dynamics in generalized HIV epidemics: an essential tool where the burden is greatest?
01 Oct 2014-Journal of Acquired Immune Deficiency Syndromes (Lippincott Williams and Wilkins)-Vol. 67, Iss: 2, pp 181-195
TL;DR: This work describes the current uses for phylogenetics in generalized epidemics and discusses their promise for elucidating transmission patterns and informing prevention trials, and reviews logistic and technical challenges inherent to large-scale molecular epidemiological studies of generalized Epidemics and suggest potential solutions.
Abstract: Efficient and effective HIV prevention measures for generalized epidemics in sub-Saharan Africa have not yet been validated at the population level. Design and impact evaluation of such measures requires fine-scale understanding of local HIV transmission dynamics. The novel tools of HIV phylogenetics and molecular epidemiology may elucidate these transmission dynamics. Such methods have been incorporated into studies of concentrated HIV epidemics to identify proximate and determinant traits associated with ongoing transmission. However, applying similar phylogenetic analyses to generalized epidemics, including the design and evaluation of prevention trials, presents additional challenges. Here we review the scope of these methods and present examples of their use in concentrated epidemics in the context of prevention. Next, we describe the current uses for phylogenetics in generalized epidemics and discuss their promise for elucidating transmission patterns and informing prevention trials. Finally, we review logistic and technical challenges inherent to large-scale molecular epidemiological studies of generalized epidemics and suggest potential solutions.
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TL;DR: A large-scale community-wide phylogenetic study to examine the underlying HIV transmission dynamics and the source and consequences of high rates of HIV infection in young women in South Africa finds sexual partnering between young women and older men, who might have acquired HIV from women of similar age, is a key feature of the sexual networks driving transmission.
230 citations
TL;DR: HIV-TRACE implements an approach inspired by traditional epidemiology, by identifying chains of partners whose viral genetic relatedness imply direct or indirect epidemiological connections, and can be applied to study outbreaks and epidemics of other rapidly evolving pathogens.
Abstract: 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.
190 citations
TL;DR: It is concluded that genetic linkage provides more reliable evidence for identifying potential transmission partners than partner naming, highlighting the importance and complementarity of both epidemiological and molecular genetic surveillance for characterizing regional HIV-1 epidemics.
Abstract: CITATION: Wertheim, J. O. et al. 2017. Social and genetic networks of HIV-1 transmission in New York City. PLoS Pathogens, 13(1): e1006000, doi:10.1371/journal.ppat.1006000.
154 citations
TL;DR: The data suggest that HIV infections among heterosexual women predominantly originate from MSM, followed by heterosexual men, and interventions that reduce transmissions involving MSM are likely to also reduce HIV acquisition among other risk groups.
Abstract: BACKGROUND Studying HIV transmission networks provides insight into the spread of HIV and opportunities for intervention. We identified transmission dynamics among risk groups and racial/ethnic groups in the United States. METHODS For HIV-1 pol sequences reported to the US National HIV Surveillance System during 2001-2012, we calculated pairwise genetic distance, identified linked pairs of sequences (those with distance ≤1.5%), and examined transmission category and race/ethnicity of these potential transmission partners. RESULTS Of 40,950 sequences, 12,910 (32%) were linked to ≥1 other sequence. Of men who have sex with men (MSM) who were linked to ≥1 sequence, 88% were linked to other MSM and only 4% were linked to heterosexual women. Of heterosexual women for whom we identified potential transmission partners, 29% were linked to MSM, 21% to heterosexual men, and 12% to persons who inject drugs. Older and black MSM were more likely to be linked to heterosexual women. Assortative mixing was present for all racial/ethnic groups; 81% of blacks/African Americans linked to other blacks. CONCLUSIONS This analysis is the first use of US surveillance data to infer an HIV transmission network. Our data suggest that HIV infections among heterosexual women predominantly originate from MSM, followed by heterosexual men. Although few MSM were linked to women, suggesting that a minority of MSM are involved in transmission with heterosexual women, these transmissions represent a substantial proportion of HIV acquisitions by heterosexual women. Interventions that reduce transmissions involving MSM are likely to also reduce HIV acquisition among other risk groups.
131 citations
TL;DR: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI), and diagnostic, clinical, and public health implications of identifying and treating persons with AHI are examined.
Abstract: Introduction: The unchanged global HIV incidence may be related to ignoring acute HIV infection (AHI). This scoping review examines diagnostic, clinical, and public health implications of identifying and treating persons with AHI.
Methods: We searched PubMed, in addition to hand-review of key journals identifying research pertaining to AHI detection and treatment. We focused on the relative contribution of AHI to transmission and the diagnostic, clinical, and public health implications. We prioritized research from low- and middle-income countries (LMICs) published in the last fifteen years.
Results and Discussion: Extensive AHI research and limited routine AHI detection and treatment have begun in LMIC. Diagnostic challenges include ease-of-use, suitability for application and distribution in LMIC, and throughput for high-volume testing. Risk score algorithms have been used in LMIC to screen for AHI among individuals with behavioural and clinical characteristics more often associated with AHI. However, algorithms have not been implemented outside research settings. From a clinical perspective, there are substantial immunological and virological benefits to identifying and treating persons with AHI – evading the irreversible damage to host immune systems and seeding of viral reservoirs that occurs during untreated acute infection. The therapeutic benefits require rapid initiation of antiretrovirals, a logistical challenge in the absence of point-of-care testing. From a public health perspective, AHI diagnosis and treatment is critical to: decrease transmission via viral load reduction and behavioural interventions; improve pre-exposure prophylaxis outcomes by avoiding treatment initiation for HIV-seronegative persons with AHI; and, enhance partner services via notification for persons recently exposed or likely transmitting.
Conclusions: There are undeniable clinical and public health benefits to AHI detection and treatment, but also substantial diagnostic and logistical barriers to implementation and scale-up. Effective early ART initiation may be critical for HIV eradication efforts, but widespread use in LMIC requires simple and accurate diagnostic tools. Implementation research is critical to facilitate sustainable integration of AHI detection and treatment into existing health systems and will be essential for prospective evaluation of testing algorithms, point-of-care diagnostics, and efficacious and effective first-line regimens.
102 citations
Cites background from "Phylogenetic studies of transmissio..."
...[48] Dennis AM, Herbeck JT, Brown AL, Kellam P, De Oliveira T, Pillay D, et al....
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...vaginal intercourse) by region and population [48]....
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References
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University of North Carolina at Chapel Hill1, Fred Hutchinson Cancer Research Center2, FHI 3603, University of Zimbabwe4, Johns Hopkins University5, Oswaldo Cruz Foundation6, Chiang Mai University7, Fenway Health8, Harvard University9, Kenya Medical Research Institute10, University of the Witwatersrand11, University of California, San Francisco12, University of Nebraska Medical Center13, National Institutes of Health14, University of California, Los Angeles15, University of Washington16
TL;DR: In this article, Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.
Abstract: Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we...
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TL;DR: The exciting evidence generated by this paper – that antiretroviral treatment of HIV-1 infection definitively reduces the risk of onward transmission of the virus by 96% – was rightly dubbed Science magazine's ‘Breakthrough of the Year’ in 2011.
Abstract: MS Cohen, YQ Chen, M McCauley N Engl J Med 2011 365:493–505.
The exciting evidence generated by this paper – that antiretroviral treatment of HIV-1 infection definitively reduces the risk of onward transmission of the virus by 96% – was rightly dubbed Science magazine's ‘Breakthrough of the Year’ in 2011.1 ,2
It has long been known that the probability of sexual transmission of HIV is strongly correlated with concentrations of HIV in blood and genital fluids.3 ,4 Effective antiretroviral therapy (ART) produces prolonged and sustained suppression of HIV replication in these compartments, reducing the amount of free virus.5 ,6 Thus, there has long been a …
4,259 citations
"Phylogenetic studies of transmissio..." refers background in this paper
...Prevention, TasP) has garnered excitement as a means to curb the spread of the virus.(3) A recent population-based cohort study conducted in a high prevalence region in KwaZulu-Natal found...
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TL;DR: The Bayesian skyline plot is introduced, a new method for estimating past population dynamics through time from a sample of molecular sequences without dependence on a prespecified parametric model of demographic history, and a Markov chain Monte Carlo sampling procedure is described that efficiently samples a variant of the generalized skyline plot, given sequence data.
Abstract: We introduce the Bayesian skyline plot, a new method for estimating past population dynamics through time from a sample of molecular sequences without dependence on a prespecified parametric model of demographic history. We describe a Markov chain Monte Carlo sampling procedure that efficiently samples a variant of the generalized skyline plot, given sequence data, and combines these plots to generate a posterior distribution of effective population size through time. We apply the Bayesian skyline plot to simulated data sets and show that it correctly reconstructs demographic history under canonical scenarios. Finally, we compare the Bayesian skyline plot model to previous coalescent approaches by analyzing two real data sets (hepatitis C virus in Egypt and mitochondrial DNA of Beringian bison) that have been previously investigated using alternative coalescent methods. In the bison analysis, we detect a severe but previously unrecognized bottleneck, estimated to have occurred 10,000 radiocarbon years ago, which coincides with both the earliest undisputed record of large numbers of humans in Alaska and the megafaunal extinctions in North America at the beginning of the Holocene.
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"Phylogenetic studies of transmissio..." refers background in this paper
...Phylodynamics is the use of pathogen sequences to reconstruct epidemic history using viral genealogies and explicit population genetic models.(120,122,123) Despite great methodological potential and scientific interest, phylodynamics has to date been rarely used for impact evaluation....
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TL;DR: The CD4 cell count at initiation was the dominant prognostic factor in patients starting HAART, and should be taken into account in future treatment guidelines.
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TL;DR: A phylodynamic framework for the dissection of dynamic forces that determine the diversity of epidemiological and phylogenetic patterns observed in RNA viruses of vertebrates is introduced.
Abstract: A key priority for infectious disease research is to clarify how pathogen genetic variation, modulated by host immunity, transmission bottlenecks, and epidemic dynamics, determines the wide variety of pathogen phylogenies observed at scales that range from individual host to population. We call the melding of immunodynamics, epidemiology, and evolutionary biology required to achieve this synthesis pathogen “phylodynamics.” We introduce a phylodynamic framework for the dissection of dynamic forces that determine the diversity of epidemiological and phylogenetic patterns observed in RNA viruses of vertebrates. A central pillar of this model is the Evolutionary Infectivity Profile, which captures the relationship between immune selection and pathogen transmission.
1,248 citations
"Phylogenetic studies of transmissio..." refers background in this paper
...Phylodynamics is the use of pathogen sequences to reconstruct epidemic history using viral genealogies and explicit population genetic models.(120,122,123) Despite great methodological potential and scientific interest, phylodynamics has to date been rarely used for impact evaluation....
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