A rapid integrated method to monitor HIV viral load drug resistance and transmission patterns from fingerprick blood samples Dr Sandra E Chaudron Big Data Institute and Welcome Centre for Human Genetics ID: 1046051
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1. Session OAC01: Real-time HIV surveillance to achieve Fast-Track milestonesA rapid, integrated method to monitor HIV viral load, drug resistance, and transmission patterns from finger-prick blood samples Dr. Sandra E. ChaudronBig Data Institute and Welcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, United Kingdomaids2022.org AIDS Conference 2022 Montreal, 31.07.20221
2. Decrease community-level HIV incidencePrevention interventionsMolecular EpidemiologyModelling Projections>22k whole HIV genomesDrivers of on-going transmissionChanging patterns in drug resistanceHall et al, MedRxiv, 202125-40y/o men are missing in the care cascade and account for 40% transmissionsWymant et al, Science, 2022Highly virulent variant of subtype-B HIV-1 An increasing proportion of new infections will come from ART experienced people who have been infected for longer. Background Rationale Method Results Conclusion Acknowledgement2
3. People Living with Infectious diseaseHealth Care ProvidersPolicy- makersAMPHEUSAnalytics and Microbiology for Precision Health and Epidemiology – A Unified SolutionAn integrated laboratory systemHIV Viral Load + Drug Resistance + Recency + Transmission + PhylogeneticsPhylogeneticsTransmission networksViral loadDrug resistance Background Rationale Method Results Conclusion Acknowledgement3
4. Diagnostics + Public HealthReal-time monitoring of drug resistance, transmission patterns, and co-infectionsTimely delivery of dataSame day viral load (≈$10)Batched sequencing (≈$20)48 – 72 hrsSelf-collect blood sampling(eg. finger prick)Digital health integration(eg. Phone apps and vending machines)A ‘clinic-light’ solutionLink to existing clinical systemsAugment, not replace existing systemsIntegration with public health dashboards and periodic reportingOpportunities for researchHigh and low throughputUp to 1000 viral load tests per day 384 – 1500 sequences per weekPathogen-agnostic, metagenomic-basedEndemic disease management withintegrated pathogen surveillanceAllows instant ‘pivot’ to outbreak responseTested on RNA + DNA pathogens(HBV, RSV, SARS-COV-2, HIV, HCV)15k SARS-COV-2 sequences to COG-UK, AZ-vaccine research and UK surveillanceFast &Cost-effectiveAppealingAccessibleNetworkedScalableMulti-pathogenIntegratedIntegratedFast &Cost-effectiveAppealingAccessibleNetworkedScalableMulti-PathogenAMPHEUS(specification) Background Rationale Method Results Conclusion Acknowledgement4
5. Nucleic acid extractionLibrary preparation with integrated viral loadProbe enrichment of viraemic librariesSequencingBioinformatics Molecular epidemiologyLow-volume blood collectionLow-volume blood collectionNucleic acid extractionLibrary preparation with integrated viral loadProbes enrichment of viraemic librariesSequencingBioinformatics Molecular epidemiologyAMPHEUS(Methods)Report viral loadRoute viraemic samples for sequencingProbe enrichment of batched viraemic samples Increases sensitivity and reduces cost Background Rationale Method Results Conclusion Acknowledgement5
6. Assay quantitativity and sequencing sensitivity Background Rationale Method Results Conclusion AcknowledgementPX Study~200 copies in the reaction ~1000 copies in the reaction6
7. Phyloscanner (Wymant, Hall et al., Molecular Biology and Evolution, 2017)PacBioIlluminaPhylogenetics to characterize HIV-1 transmission Background Rationale Method Results Conclusion Acknowledgement7
8. Data adapted from Dr. Lele ZhaoA sensitive assay to characterise HIV-1 linked transmission pairs Background Rationale Method Results Conclusion Acknowledgement8
9. Background Rationale Method Results Conclusion AcknowledgementTake-home message on the AMPHEUS platform Integrated platform using low volume blood samples for rapid diagnostics and whole genome sequencingHigh-resolution molecular epidemiological data with transmission source attribution – Improved with PacBIO long read sequencingLow cost and high throughputEpidemic/pandemic response and preparednessImplementation of the platform in Zambia9
10. Co-authors:David BonsallChristophe FraserLele ZhaoGeorge Macintyre-Cockett Anna JeffreysLaura ThompsonIan BaudiKwitaka MaluziMohammed LimbadaSian FloydBarry KosloffKwame ShanaubeSarah FidlerRichard HayesHelen AylesJoshua HerbeckThe PANGEA ConsortiumThe AMPHEUS research groupMembers of the Bonsall and Fraser GroupOxford Genomic Centre Background Rationale Method Results Conclusion Acknowledgement10