Pont-of-use Acute HIV Infection Diagnostic for Substance Using Populations
针对药物使用人群的使用点急性 HIV 感染诊断
基本信息
- 批准号:10794830
- 负责人:
- 金额:$ 28.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-07-01 至 2024-06-30
- 项目状态:已结题
- 来源:
- 关键词:3&apos Untranslated RegionsAccelerationAcuteAcute HepatitisAcute Hepatitis CAntibodiesAttitudeBiological AssayBloodBlood capillariesBlood specimenBuffersCessation of lifeChronic Hepatitis CClinicClinicalCold ChainsContinuity of Patient CareCytolysisDetectionDevelopmentDevicesDiagnosisDiagnosticDiagnostic testsDropsDrug userDrynessElementsExposure toFeedbackGenomeGoalsHIVHIV InfectionsHIV diagnosisHIV-1HIV/HCVHealthcareHeatingHepatitis CHepatitis C AntibodiesHepatitis C TransmissionHepatitis C virusHumanHuman immunodeficiency virus testIndividualInfectionInfrastructureInjectionsInterventionKentuckyLaboratoriesLiver CirrhosisLiver diseasesMarketingMicrofluidicsNeedle-Exchange ProgramsNucleic Acid Amplification TestsPaperPharmaceutical PreparationsPharmacy facilityPlasmaPopulationPreparationProcessProteinsProtocols documentationRNARapid diagnosticsReactionReagentResistanceReverse Transcriptase Polymerase Chain ReactionRunningRuralRural HealthSamplingSiteTechnologyTestingTimeUntranslated RNAViralViral Load resultVirusVisualWaxesWhole Bloodacceptability and feasibilityacute infectionanti-hepatitis Cantibody detectionbarrier to careclinically relevantcommunity based participatory researchdesigndetection limithealth care availabilityhigh riskimprovedlateral flow assaynovelnovel strategiesparent grantparticlepreventprototypeservice providerssociocultural determinantsubstance abuse treatmentsubstance usesystemic barriertechnology platformtransmission processusabilityviron
项目摘要
Parent Grant: 1DP2DA051910
Parent Grant Title: Point-of-use Acute HIV Infection Diagnostic for Substance Using Populations
Supplement Title: Expansion of Point-of-use Acute HIV Infection platform for Hepatitis C Virus
An estimated 2.3 million individuals with HIV infection are co-infected with hepatitis C (HCV). In the US, people who
use drugs (PWUD) are at high risk for both infections. HIV accelerates liver cirrhosis caused by HCV and contributes to
the 350,000 deaths that occur due to HCV-related liver disease each year. Unfortunately, existing widely used rapid
diagnostic tests (RDTs) for HCV do not detect the virus itself but instead detect only the anti-HCV antibodies produced
by the infected individual. This antibody-based detection presents two challenges. First, host antibodies develop long after
initial exposure to HCV which can allow for infections to remain undetected and potentially spread to other individuals.
Second, anti-HCV antibodies remain even after HCV clearance and can result in false positive results that do not
differentiate a current infection from a past infection. In contrast, test targeting the virus itself, such as nucleic acid
amplification tests (e.g. RT-PCR), have the potential to detect both acute and chronic HCV infections. However, these
assays typically require cold-chain storage of reagents, significant sample preparation, and extensive laboratory
infrastructure to run. While PWUD are willing to get tested for HIV and HCV at non-traditional sites such as rural
pharmacies (Duong et al 2019), current laboratory-based RT-PCR tests are unable to reach these individuals who are
already underserved by traditional healthcare. Thus, there is an urgent need for a radically new approach to diagnose HCV
among PWUD in order to engage infected individuals in the care continuum at the earliest stages of infection and prevent
progression and transmission of HCV.
In this supplement, we propose to adapt our current platform technology for acute HIV or order to to detect acute HCV
thresholds above the clinically relevant 3000 HCV IU/mL (Reipold et al 2017) at point-of-use settings. Our ongoing DP2
is based on our handheld sample-to-answer technology, an automated microfluidic rapid autonomous analytical device
(microRAAD). We have demonstrated that microRAAD is capable of detecting HIV virons directly from a whole blood
samples. We incorporated dried amplification reagents and wax valves in paper-based substrates with resistive heating
elements and low-power circuitry. By combining feedback-controlled heating of the RT-LAMP assay and wax valves
with paper’s capillary flow, our assembled device automatically isolates viral particles from human blood, lysis the virus,
amplifies HIV-1 RNA, and transports products to a detection zone with familiar visual lateral flow assay readout.
This entire process requires only 3 simple steps for the user: first, a drop of blood is added to the sample pad, next, the
user dispenses a buffer solution, and after a brief waiting period, the user reads the visual yes/no result. We have
demonstrated that the fully integrated microRAAD detects as few as 10^5 HIV-1 vp/reaction directly from whole blood in
under 90 minutes. In the ongoing DP2, we are working with local populations of PWUD and HIV service providers to
evaluate feasibility, acceptability, and usability of the technology and to further reduce this detection to below 10^3 HIV
vp/mL by combining p24 protein-based targeting and RT-LAMP together as well as improving clinical relevance via
integration of an internal amplification control.
Our next steps to adapt MicroRAAD to acute HCV detection will include:
1) Develop and optimize a novel assay for HCV detection targeting the conserved regions of the genome. For HCV assay
design we will compare the 5’non-coding region (5’-NCR) and the 3’untranslated region (3’UTR) which have both been
used in clinical HCV viral load assays. While the 5’-NCR is used in western assays, it’s known that the variability in this
region is somewhat divergent from the sequences circulating worldwide. Therefore, we will also consider the 3’UTR for
RT-LAMP design. We will generate at least two primers to each region and will compare the time to amplification (TTA),
limit of detection (spiking in 0-10^7 IU/mL of synthetic RNA purchased from ATCC), and resistance to whole blood and
plasma spiked into each sample at concentrations ranging from 0-20%.
2) Expand our community-based participatory research with PWUD and their service providers to evaluate HCV-focused
detection at the point-of-use in concert with HIV detection. This will include performing feasibility and acceptability
studies to evaluate the operational, clinical, and market needs specific for HCV detection by and for PWUD at the POU,
evaluate how socio-cultural factors and systemic barriers to care among PWUD impact their HCV testing and integration
into the current HIV care continuum and assess usability of device prototypes to determine the best operational protocols
among stakeholders.
This platform for point-of-use HCV/HIV detection could transform both testing and treatment of HIV and HCV among
PWUD by bringing acute infection detection to substance abuse treatment facilities, needle exchanges, and injection drug
clinics and will elucidate the targeted interventions needed to remove barriers to care.
References:
Reipold IE, Easterbrook P, Trianni A, Panneer N, Krakower D, Ongarello S, Roberts T, Miller V, Denkinger C.
Optimising diagnosis of viraemic hepatitis C infection: the development of a target product profile. BMC Infect Dis. 2017
Nov 1;17(Suppl 1):707. doi: 10.1186/s12879-017-2770-5. PMID: 29143620; PMCID: PMC5688443.
Duong M, Delcher C, Freeman PR, Young AM, Cooper HLF. Attitudes toward pharmacy-based HCV/HIV testing among
people who use drugs in rural Kentucky. J Rural Health. 2022 Jan;38(1):93-99. doi: 10.1111/jrh.12564. Epub 2021 Mar 5.
PMID: 33666274; PMCID: PMC8418619.
父授:1DP2DA051910
项目成果
期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Measurement of Protein-Protein Interaction Dynamics Using Microfluidics and Particle Diffusometry.
- DOI:10.1021/acs.analchem.2c02570
- 发表时间:2022-11-15
- 期刊:
- 影响因子:7.4
- 作者:Ma, Hui;Wereley, Steven T.;Linnes, Jacqueline C.;Kinzer-Ursem, Tamara L.
- 通讯作者:Kinzer-Ursem, Tamara L.
Thinking Beyond the Device: An Overview of Human- and Equity-Centered Approaches for Health Technology Design.
- DOI:10.1146/annurev-bioeng-081922-024834
- 发表时间:2023-06-08
- 期刊:
- 影响因子:9.7
- 作者:
- 通讯作者:
From Crisis To Crisis: Impacts Of The COVID-19 Pandemic On People Living With HIV And AIDS Service Organizations In Indiana.
从危机到危机:COVID-19 大流行对印第安纳州艾滋病毒感染者和艾滋病服务组织的影响。
- DOI:10.21203/rs.3.rs-1003567/v1
- 发表时间:2022
- 期刊:
- 影响因子:0
- 作者:MacNeill,JustinJ;Linnes,JacquelineC;Rodriguez,NataliaM
- 通讯作者:Rodriguez,NataliaM
From crisis to crisis: impacts of the COVID-19 pandemic on people living with HIV and HIV/AIDS service organizations in Indiana.
- DOI:10.1186/s12913-022-07998-0
- 发表时间:2022-05-09
- 期刊:
- 影响因子:2.8
- 作者:MacNeill, Justin J.;Linnes, Jacqueline C.;Hubach, Randolph D.;Rodriguez, Natalia M.
- 通讯作者:Rodriguez, Natalia M.
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Jacqueline Linnes其他文献
Jacqueline Linnes的其他文献
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{{ truncateString('Jacqueline Linnes', 18)}}的其他基金
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- 批准号:
10443827 - 财政年份:2020
- 资助金额:
$ 28.93万 - 项目类别:
Point-of-care screening test for early cervical cancer detection
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10267737 - 财政年份:2020
- 资助金额:
$ 28.93万 - 项目类别:
Pont-of-use Acute HIV Infection Diagnostic for Substance Using Populations
针对药物使用人群的使用点急性 HIV 感染诊断
- 批准号:
10056083 - 财政年份:2020
- 资助金额:
$ 28.93万 - 项目类别:
Point-of-care screening test for early cervical cancer detection
用于早期宫颈癌检测的护理点筛查测试
- 批准号:
10650144 - 财政年份:2020
- 资助金额:
$ 28.93万 - 项目类别:
Smartphone-based diagnostic for HIV self-testing
基于智能手机的 HIV 自检诊断
- 批准号:
10455110 - 财政年份:2018
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Smartphone-based diagnostic for HIV self-testing
基于智能手机的 HIV 自检诊断
- 批准号:
10423656 - 财政年份:2018
- 资助金额:
$ 28.93万 - 项目类别:
Smartphone-based diagnostic for HIV self-testing
基于智能手机的 HIV 自检诊断
- 批准号:
9756313 - 财政年份:2018
- 资助金额:
$ 28.93万 - 项目类别:
A Rapid Instrument Free Molecular Diagnostic for B. Pertussis
百日咳博德特氏菌的快速无仪器分子诊断
- 批准号:
8718586 - 财政年份:2014
- 资助金额:
$ 28.93万 - 项目类别:
A Rapid Instrument Free Molecular Diagnostic for B. Pertussis
百日咳博德特氏菌的快速无仪器分子诊断
- 批准号:
8802766 - 财政年份:2014
- 资助金额:
$ 28.93万 - 项目类别:
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