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Revealing the Phylodynamics of HIV-1 in Australia

English title Revealing the Phylodynamics of HIV-1 in Australia
Applicant Di Giallonardo Francesca
Number 174462
Funding scheme Advanced Postdoc.Mobility
Research institution Immunovirology and Pathogenesis Program The Kirby Institute University of New South Wales
Institution of higher education Institution abroad - IACH
Main discipline Molecular Biology
Start/End 01.01.2018 - 30.06.2019
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All Disciplines (3)

Discipline
Molecular Biology
Infectious Diseases
Genetics

Keywords (4)

phylogenetics; prevention; HIV-1; emergence

Lay Summary (German)

Lead
Das Humane Immundefizienz-Virus Typ 1 (HIV-1) ist die Ursache der schwerwiegenden Pandemie Acquired Immunodeficiency Syndrome (AIDS), welche erstmals in 1981 auftrat. Leider existiert bis heute weder eine Heilung noch eine Impfung und in den letzten 30 Jahren sind über 30 Millionen Menschen an AIDS gestorben. Glücklicherweise ist eine Therapie möglich, welche Menschen mit AIDS eine normale Lebenserwartung ermöglicht. Dank dieser antiretroviralen Therapie (ART) ist die Anzahl HIV positiver Menschen stark gesunken und in manchen westlichen Länder hat diese Therapie sogar das auftreten von AIDS extrem reduziert. Jedoch ist in den letzten zehn Jahren die HIV-Übertragungsrate wieder leicht angestiegen und eine Ausrottung von HIV scheint in weiter Ferne.
Lay summary

Titel des Forschungsprojekts

Die Evolution und Phylogenie von HIV in Australien

L’evoluzione e la filogenesi dell’HIV in Australia

L’évolution et la phylogénie du VIH en Australie

 

Lead

Das Humane Immundefizienz-Virus Typ 1 (HIV-1) ist die Ursache der schwerwiegenden Pandemie Acquired Immunodeficiency Syndrome (AIDS), welche erstmals in 1981 auftrat. Leider existiert bis heute weder eine Heilung noch eine Impfung und in den letzten 30 Jahren sind über 30 Millionen Menschen an AIDS gestorben. Glücklicherweise ist eine Therapie möglich, welche Menschen mit AIDS eine normale Lebenserwartung ermöglicht. Dank dieser antiretroviralen Therapie (ART) ist die Anzahl HIV positiver Menschen stark gesunken und in manchen westlichen Länder hat diese Therapie sogar das auftreten von AIDS extrem reduziert. Jedoch ist in den letzten zehn Jahren die HIV-Übertragungsrate wieder leicht angestiegen und eine Ausrottung von HIV scheint in weiter Ferne.

 

 

Inhalt und Ziel des Forschungsprojekts

Dieses Forschungsprojekt untersucht die Evolution und Übertragungsrate von HIV in verschiedenen Risikogruppen in Australien. Eine Datenbank ist nun verfügbar, welche die genetische Information von HI Viren mit den epidemiologischen Faktoren der Patienten verknüpft. Dies ermöglicht eine detaillierte Analyse der Evolutionsfaktoren welche die Epidemie in Australien geprägt haben.

Ziel dieses Forschungsprojekt ist zu verstehen weshalb die HIV-Übertragungsrate trotz erfolgreicher ART nicht weiter sink. Ausserdem wird untersucht ob neue Präventionsstrategien tatsächlich von Vorteil sind und die HIV-Rate senken.

 

Wissenschaftlicher und gesellschaftlicher Kontext des Forschungsprojekts

Dieses Projekt wird den Einfluss von Präventionsstrategien auf die HIV Evolution und Übertragungsrate untersuchen. Die Resultate werden die Grenzen der HIV Prävention offenbaren und zeigen welche Faktoren die HIV Rate am meisten beeinflussen. 

 

Key words

Phylogenetics, prevention, HIV-1, emergence

Direct link to Lay Summary Last update: 28.06.2017

Responsible applicant and co-applicants

Publications

Publication
Limited Sustained Local Transmission of HIV-1 CRF01_AE in New South Wales, Australia.
Di Giallonardo Francesca, Pinto Angie N, Keen Phillip, Shaik Ansari, Carrera Alex, Salem Hanan, Telfer Barbara, Cooper Craig, Price Karen, Selvey Christine, Holden Joanne, Bachmann Nadine, Lee Frederick J, Dwyer Dominic E, Duchêne Sebastián, Holmes Edward C, Grulich Andrew E, Kelleher Anthony D (2019), Limited Sustained Local Transmission of HIV-1 CRF01_AE in New South Wales, Australia., in Viruses, 11(5), 482.
A10 Using the molecular epidemiology of HIV transmission in New South Wales to inform public health response: Assessing the representativeness of linked phylogenetic data
PintoAngie, Di GiallonardoFrancesca, KeenPhillip, CooperCraig, TelferBarbara, Cooper David, GrulichAndrew, KelleherAnthony (2018), A10 Using the molecular epidemiology of HIV transmission in New South Wales to inform public health response: Assessing the representativeness of linked phylogenetic data, in Virus Evolution, 4(suppl_1), vey010.009.

Datasets

Limited Sustained Local Transmission of HIV-1 CRF01_AE in New South Wales, Australia

Author Di Giallonardo, Francesca; Pinto, Angie N.; Keen, Phillip; Shaik, Ansari; Carrera, Alex; Salem, Hanan; Telfer, Barbara; Cooper, Craig; Price, Karen; Selvey, Christine; Holden, Joanne; Bachmann, Nadine; Lee, Frederick J.; Dwyer, Dominic E.; Duchêne, Sebastián; Holmes, Edward C.; Grulich, Andrew E.; Kelleher, Anthony D.
Publication date 27.05.2019
Persistent Identifier (PID) MK941065-MK941134
Repository NCBI
Abstract
Australia’s response to the human immunodeficiency virus type 1 (HIV-1) pandemic led to effective control of HIV transmission and one of the world’s lowest HIV incidence rates-0.14%. Although there has been a recent decline in new HIV diagnoses in New South Wales (NSW), the most populous state in Australia, there has been a concomitant increase with non-B subtype infections, particularly for the HIV-1 circulating recombinant form CRF01_AE. This aforementioned CRF01_AE sampled in NSW, were combined with those sampled globally to identify NSW-specific viral clades. The population growth of these clades was assessed in two-year period intervals from 2009 to 2017. Overall, 109 NSW-specific clades were identified, most comprising pairs of sequences; however, five large clades comprising ≥10 sequences were also found. Forty-four clades grew over time with one or two sequences added to each in different two-year periods. Importantly, while 10 of these clades have seemingly discontinued, the remaining 34 were still active in 2016/2017. Seven such clades each comprised ≥10 sequences, and are representative of individual sub-epidemics in NSW. Thus, although the majority of new CRF01_AE infections were associated with small clades that rarely establish ongoing chains of local transmission, individual sub-epidemics are present and should be closely monitored.

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
Australasian HIV & AIDS Conference Poster Local geographic differences in long-lasting HIV-1 clusters in New South Wales 24.09.2018 Sydney, Australia Di Giallonardo Francesca;
Virus Genomics and Evolution Poster Local geographic differences in long lasting HIV-1 clusters in New South Wales, Australia 18.06.2018 Cambridge, Great Britain and Northern Ireland Di Giallonardo Francesca;


Associated projects

Number Title Start Funding scheme
151594 DIVERSITY, EVOLUTION AND CONTROL OF DENGUE VIRUS 01.04.2014 Early Postdoc.Mobility

Abstract

The human immunodeficiency virus 1 (HIV-1) causes 2.1 million new infections each year. Although antiretroviral therapy (ART) has been a success in reducing the HIV-1 burden, only ~50% of infected people worldwide receive treatment. This number is higher in western countries with an estimated 93% and 84% of known HIV-1 positive patients receiving ART in Switzerland and Australia, respectively. Notably, there has been an increase in new infection in both countries, indicative that current treatment and prevention strategies are not sufficient in reducing the incidence of HIV-1. While Switzerland is renowned for its comprehensive HIV cohort study (SHCS) that links the molecular data to the epidemiological data, a similar database is yet to be established in Australia. In that regard, there is a profound knowledge-gap regarding the HIV-1 phylodynamics in Australia. In this study I will use the ‘linkage database’ that is now available for the HIV-1 sequences in New South Wales (NSW) to decipher the evolutionary patterns of HIV-1 over the past 20 years. In the project presented here I propose the following aims to resolve the uncertainties regarding the HIV-1 evolution dynamics in Australia: (i) uncover the HIV-1 transmission dynamics in Australia, (ii) evaluate the HIV-1 population structure in different risk groups, and (iii) assess the impact of preventive interventions on the transmission rate of HIV-1. To resolve these issues I will use virus sequence data from the NSW HIV reference laboratories that perform all the genotypic antiretroviral resistance testing (GART) and the NSW HIV register that contains epidemiological data, both of which have been included into the linkage database. I will also use public available HIV-1 sequences from the Los Alamos HIV sequence database. I will perform phylogenetic analysis using maximum likelihood and Bayesian methods to infer phylogenetic trees and virus population structure. The results will uncover the evolutionary history of HIV-1 in Australia; in particular the changes in genetic diversity, virus population size, and basic reproductive number (R0) over time. These changes will reflect the effect of public health interventions that have been implemented at the clinical-level on the evolutionary development at a molecular level. Of particular interest is the efficacy of the ‘test and treat’ strategy on the different risk groups and the pre-exposure prophylaxis (PrEP) on men who have sex with men. The comparison of the phylogenetic markers for risk groups and the transmission rate estimates within and between these groups are central for the understanding of the transmission dynamics between risk groups, which in turn can affect the impact of preventive measurements. Finally, the changes on the evolutionary patterns of HIV-1 will provide a detailed view of the phylodynamics of the virus population over time, in particular the population size, potential transmission clusters, and infection rate and how these factors have been shaped by public health interventions.
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