title: Phylogenetic Tools for Generalized HIV-1 Epidemics: Findings from the PANGEA-HIV Methods Comparison.
abstract: Viral phylogenetic methods contribute to understanding how HIV spreads in populations, and thereby help guide the design of prevention interventions. So far, most analyses have been applied to well-sampled concentrated HIV-1 epidemics in wealthy countries. To direct the use of phylogenetic tools to where the impact of HIV-1 is greatest, the Phylogenetics And Networks for Generalized HIV Epidemics in Africa (PANGEA-HIV) consortium generates full-genome viral sequences from across sub-Saharan Africa. Analyzing these data presents new challenges, since epidemics are principally driven by heterosexual transmission and a smaller fraction of cases is sampled. Here, we show that viral phylogenetic tools can be adapted and used to estimate epidemiological quantities of central importance to HIV-1 prevention in sub-Saharan Africa. We used a community-wide methods comparison exercise on simulated data, where participants were blinded to the true dynamics they were inferring. Two distinct simulations captured generalized HIV-1 epidemics, before and after a large community-level intervention that reduced infection levels. Five research groups participated. Structured coalescent modeling approaches were most successful: phylogenetic estimates of HIV-1 incidence, incidence reductions, and the proportion of transmissions from individuals in their first 3 months of infection correlated with the true values (Pearson correlation > 90%), with small bias. However, on some simulations, true values were markedly outside reported confidence or credibility intervals. The blinded comparison revealed current limits and strengths in using HIV phylogenetics in challenging settings, provided benchmarks for future methods' development, and supports using the latest generation of phylogenetic tools to advance HIV surveillance and prevention.
authors.affiliation: Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analyses and Modelling, School of Public Health, Imperial College London, London, United Kingdom oliver.ratmann@imperial.ac.uk.
authors.forename: Oliver
authors.initials: O
authors.lastname: Ratmann
authors.affiliation: School of Biological Sciences, Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Emma B
authors.initials: EB
authors.lastname: Hodcroft
authors.affiliation: Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analyses and Modelling, School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Pickles
authors.affiliation: Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analyses and Modelling, School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Anne
authors.initials: A
authors.lastname: Cori
authors.affiliation: School of Biological Sciences, Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom.|Nuffield Department of Medicine, Li Ka Shing Centre for Health Information and Discovery, Oxford Big Data Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Matthew
authors.initials: M
authors.lastname: Hall
authors.affiliation: School of Biological Sciences, Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom.|The Roslin Institute, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Samantha
authors.initials: S
authors.lastname: Lycett
authors.affiliation: Department of Mathematics, Imperial College London, London, United Kingdom.
authors.forename: Caroline
authors.initials: C
authors.lastname: Colijn
authors.affiliation: Department of Veterinary Medicine, Cambridge Veterinary School, Cambridge, United Kingdom.
authors.forename: Bethany
authors.initials: B
authors.lastname: Dearlove
authors.affiliation: Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analyses and Modelling, School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Xavier
authors.initials: X
authors.lastname: Didelot
authors.affiliation: Department of Veterinary Medicine, Cambridge Veterinary School, Cambridge, United Kingdom.
authors.forename: Simon
authors.initials: S
authors.lastname: Frost
authors.affiliation: Department of Veterinary Medicine, Cambridge Veterinary School, Cambridge, United Kingdom.
authors.forename: A S Md Mukarram
authors.initials: AS
authors.lastname: Hossain
authors.affiliation: Department of Medicine, University of British Columbia, Vancouver, BC, Canada.|British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Joy
authors.affiliation: Department of Mathematics, Imperial College London, London, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: Kendall
authors.affiliation: Department of Environmental Systems Science, ETH Zürich, Zürich, Switzerland.|Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
authors.forename: Denise
authors.initials: D
authors.lastname: Kühnert
authors.affiliation: Department of Environmental Systems Science, ETH Zürich, Zürich, Switzerland.|Department of Civil and Environmental Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA.
authors.forename: Gabriel E
authors.initials: GE
authors.lastname: Leventhal
authors.affiliation: British Columbia Centre for Excellence in HIV/AIDS, Vancouver, BC, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Liang
authors.affiliation: Department of Mathematics, Imperial College London, London, United Kingdom.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Plazzotta
authors.affiliation: Department of Pathology & Laboratory Medicine, Western University, Ontario, Canada.
authors.forename: Art F Y
authors.initials: AF
authors.lastname: Poon
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
authors.forename: David A
authors.initials: DA
authors.lastname: Rasmussen
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
authors.forename: Tanja
authors.initials: T
authors.lastname: Stadler
authors.affiliation: Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analyses and Modelling, School of Public Health, Imperial College London, London, United Kingdom.
authors.forename: Erik
authors.initials: E
authors.lastname: Volz
authors.affiliation: Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.
authors.forename: Caroline
authors.initials: C
authors.lastname: Weis
authors.affiliation: School of Biological Sciences, Institute of Evolutionary Biology, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Leigh Brown
authors.affiliation: Department of Infectious Disease Epidemiology, MRC Centre for Outbreak Analyses and Modelling, School of Public Health, Imperial College London, London, United Kingdom.|Nuffield Department of Medicine, Li Ka Shing Centre for Health Information and Discovery, Oxford Big Data Institute, University of Oxford, Oxford, United Kingdom.
authors.forename: Christophe
authors.initials: C
authors.lastname: Fraser
mesh_terms: D017954:Africa South of the Sahara / Q000453:epidemiology; D003198:Computer Simulation; D058872:Epidemics; D005260:Female; D015658:HIV Infections / Q000453:epidemiology* / Q000517:prevention & control / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008297:Male; D010802:Phylogeny
keywords: HIV transmission and prevention; molecular epidemiology of infectious diseases; viral phylogenetic methods validation