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Phylogenetic tools for generalized HIV-1 epidemics: findings from the PANGEA-HIV methods comparison

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Title: Phylogenetic tools for generalized HIV-1 epidemics: findings from the PANGEA-HIV methods comparison
Authors: Ratmann, O
Hodcroft, EB
Pickles, M
Cori, A
Hall, M
Lycett, S
Colijn, C
Dearlove, B
Didelot, X
Frost, S
Hossain, M
Joy, JB
Kendall, M
Kühnert, D
Leventhal, GE
Liang, R
Plazzotta, G
Poon, A
Rasmussen, DA
Stadler, T
Volz, E
Weis, C
Leigh Brown, AJ
Fraser, C
Item Type: Journal Article
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.
Issue Date: 7-Oct-2016
Date of Acceptance: 27-Sep-2016
URI: http://hdl.handle.net/10044/1/42696
DOI: https://dx.doi.org/10.1093/molbev/msw217
ISSN: 1537-1719
Publisher: Oxford University Press
Start Page: 185
End Page: 203
Journal / Book Title: Molecular Biology and Evolution
Volume: 34
Issue: 1
Copyright Statement: © 2016 The Authors. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Engineering & Physical Science Research Council (EPSRC)
Medical Research Council (MRC)
Funder's Grant Number: EP/K026003/1
Keywords: HIV transmission and prevention
molecular epidemiology of infectious diseases
viral phylogenetic methods validation
Evolutionary Biology
0604 Genetics
0603 Evolutionary Biology
0601 Biochemistry And Cell Biology
Publication Status: Published
Article Number: msw217v2
Appears in Collections:Mathematics
Applied Mathematics and Mathematical Physics
School of Public Health
Faculty of Natural Sciences