The overarching goal of the PANGEA consortium is to identify individual and population level factors that drive the epidemic using HIV-1 phylogenetic data, analyse the dynamics of the epidemic, and translate these findings into information that can be used to more effectively target interventions. PANGEA consists of many partners in Africa, Europe and the US.
PANGEA HIV 2
PANGEA HIV 2 is a collaboration between scientists from the Africa Health Research Institute (South Africa), Rakai Health Sciences Program (Uganda), Johns Hopkins University (USA), Medical Research Council/Uganda Virus Research Institute (Uganda), Zambart Project (Zambia), London School of Hygiene and Tropical Medicine (UK), Imperial College London (UK), Partners in Prevention Project at the University of Washington (USA), Botswana Harvard AIDS Institute Partnership (Botswana/USA), University of Edinburgh (UK), and the University of Oxford (UK).
Executive Committee: Christophe Fraser (PI), Deenan Pillay, Kate Grabowski, Andrew Rambaut
Project Management: Lucie Abeler-Dörner
Steering Committee: Helen Ayles, Lucie Abeler-Dörner, David Bonsall, Rory Bowden, Vincent Calvez, Max Essex, Sarah Fidler, Christophe Fraser, Kate Grabowski, Tanya Golubchik, Richard Hayes, Joshua Herbeck, Joseph Kagaayi, Pontiano Kaleebu, Jairam Lingappa, Vladimir Novitsky, Deenan Pillay, Thomas Quinn, Andrew Rambaut, Oliver Ratmann, Janet Seeley, Deogratius Ssemwanga, Frank Tanser, and Maria Wawer
Scientific Advisory Board: Myron Cohen, Caroline Colijn, Anne Johnson, Peter Geoffrey-Faussett, Musonda Simwinga
PANGEA has been funded in two phases by the Bill & Melinda Gates Foundation. The first phase (2013-2017) establishing the network, obtaining viral sequences and clinical data, and creating a sequence database. Over 13,000 HIV genomes were sequenced during this first phase of the project. The second phase (2017-2021) will will see the generation of more sequences, but mainly focus on analysis.
PANGEA 1 was led by Deenan Pillay, with Andrew Leigh Brown, Christophe Fraser, Paul Kellam and Tulio de Oliveira as members of the executive committee and Anne Hoppe as project manager. Members of the PANGEA 1 Steering Committee were Myron Cohen, Tulio de Oliveira, Ann Dennis, Max Essex, Sarah Fidler, Daniel Frampton, Christophe Fraser, Richard Hayes, Joshua Herbeck, Anne Hoppe, Pontiano Kaleebu, Paul Kellam, Cissy Kiyo, Andrew Leigh Brown, Jairam Lingappa, Vladimir Novitsky, Nick Paton, Deenan Pillay, Thomas Quinn, Oliver Ratmann, Deogratius Sseemwanga, Frank Tanser, and Maria Wawer. Members of the scientific advisory board were Kevin de Cock, Carl Dieffenbach, Eric Goosby, Simon Hay, Anne Johnson, Stuart Ray, and Christine Wasunna.
Proven HIV prevention methods are becoming increasingly available worldwide, yet there is little consensus on how to effectively deploy them, or how best to evaluate their impact. It is unknown whether treatment as prevention can be effectively targeted at either high-risk individuals or subpopulations, or what the contributions to the epidemic of different risk groups are. The role of acute and early infection is still disputed, particularly for heterosexual epidemics, and there is an increasing realisation that movement and migration may be an important epidemic driver.
Sources and sinks
An epidemic can be described by a model of connected sources, sinks, and hubs. Sources are groups in a population that disproportionately pass on infections, sinks are groups that disproportionately receive infections, and hubs are both sources and sinks. Population groups can be defined by age, gender, riskiness of sexual behaviour, geography, occupation, cultural preferences and norms, migrational behaviour, or other characteristics and combinations thereof. Identifying these groups allows prevention to be tailored.
The most powerful tool available to study HIV transmission is phylogenetics. A viral phylogeny reveals who is close to whom in the transmission network. With additional epidemiological information or modelling one can identify which of these close individuals are likely sources of new infections. Following theoretical work on incorporating within-host diversity into phylogenetic inference, we have developed a tool called phyloscanner that can be used for source attribution in HIV next generation sequencing (NGS) data. Once sources have been identified with quantified uncertainty, epidemiological questions about the characteristics of transmitters can be addressed. For example, transmission networks will enable us to detect individuals that are at high risk of infecting others and quantify their contribution to transmission.
The project covers four interlinked themes: 1. Molecular Epidemiology and Mathematical Modelling, 2. Phylodynamics, 3. Mobility and Migration, and 4. Clinical Science, Drug Resistance and Ethics. The four themes correspond to four working groups that will each be led by one member of the Executive Committee.
Molecular Epidemiology and Mathematical Modelling (Christophe Fraser)
This theme is building a transmission network from the PANGEA sequences, to answer several epidemiological questions, e.g. which demographical, clinical and virological correlates identify transmitters, whether stratifying the analysis by age and gender reveals transmission cycles across different age groups, and how drug-sensitive and drug-resistant viruses are transmitted. Mathematical modelling is a key tool for designing public health interventions, but several uncertainties have been difficult to resolve in HIV models, e.g. infectiousness of acute infection, transmission patterns between age and sex groups, heterogeneity of transmission rates and the contribution of hidden risk populations. As new technologies result in more costly interventions, it becomes ever more important to estimate key parameters using phylogenetics to prioritise target groups, to assess the impact of interventions and to use models to predict their likely effect.
Phylodynamics (Andrew Rambaut)
This theme takes the analysis of phylogenetic trees a step further, looking at spatial movement patterns of the virus across cohorts and countries and the identification of ‘outbreaks’, unusually dense transmission clusters in geographically or demographically defined groups which might indicate concentrated epidemics within the epidemic. The theme will also dig deeper into the trees, linking the branching length to time, thereby identifying core groups that disproportionally spread the epidemic and assessing the impact that the stage of infection has on onward transmission. The Phylodynamics team also works on visualising the results and on further developing the analysis software used in this project. They will adopt existing phylodynamics tools to account for genetic variation and for use with large datasets.
Mobility and Migration (Kate Grabowski)
This theme investigates how mobility and migration influences the spread of the HIV epidemic in different African countries. There is growing evidence that mobile populations are at higher risk of for HIV and can sustain epidemics by not being eligible for treatment. Analysing mobility can also inform us to what extent high prevalence areas fuel epidemics in surrounding areas of low prevalence. When this happens in areas of population trials (which is the case for three of the PANGEA sites), this might impact on the interpretation of the results. Phylogenetics offers a unique way to track the spread of the virus along with mobile populations and define local sources, sinks and hubs.
Clinical Science, Drug Resistance and Ethics (Deenan Pillay)
This theme investigates why incidence in many parts of Africa is not falling as fast as expected despite a dramatic increase of antiretroviral coverage and how new prevention approaches will impact on the epidemic. It also monitors to what extent the rapidly expanding use or antiretroviral therapy is associated with the emergence of HIV drug resistance. The phylogenetic approach will make it possible to find the groups that are still at high risk of HIV infection and target them in prevention approaches. Finally, this theme will look at the ethical issues around phylogenetic studies in a highly stigmatised disease like HIV and how the risks and benefits can best be explained to study participants.
Currently the PANGEA database holds over 18,000 NGS sequence files from sub-Saharan Africa with basic epidemiological metadata associated with them. For some cohorts, extensive metadata is available; contact us for more information. We currently obtain full genomes from ~ 90% of high-quality samples, with many of the less-complete sequences originating from participants who are likely to be virally suppressed. See the resource section for sequencing protocols used.
Last updated December 2018 *Sequences from PopART Phylogenetics will become available to accredited researchers in spring 2020.
How to get involved
There are different ways in which external researchers can be involved with PANGEA. 1) Sequence your samples with PANGEA: We offer subsidised state-of-the-art NGS sequencing to collaborators who are willing to contribute their sequence data, and associated epidemiological data to the PANGEA database 12 months after they have received the data. 2) Contribute sequence data: If your project is at a stage where you are ready to reach out to a wider range of collaborators or if you are looking for a secure storing place for your data, consider contributing your sequence data to the PANGEA database. 3) Join the community of PANGEA researchers: The aim of PANGEA is to make the best possible use of the data for public health and scientific discovery, and to give credit to the people who generated the data. PANGEA therefore operates a data sharing policy that is as open as possible given the sensitivity of the data. External researchers can request access to the data via a concept sheet proposal. After six months and two successful progress updates to the consortium, researchers named on the concept sheet proposal can apply to become an accredited PANGEA researcher. Accredited PANGEA researchers have access to all sequence data and less-sensitive metadata. They are required to agree to a code of conduct and update the consortium regularly on their research. Collaborations with researchers from the institutes that generated the data are encouraged. For forms and more information, contact Lucie Abeler-Dörner (firstname.lastname@example.org)
A discussion forum for this project can be found here.
- PANGEA HIV is funded by the Bill& Melinda Gates Foundation.
- The content on this webpage does not necessarily reflect the positions or policies of the funder.