Effects of mu-opiate receptor engagement on microbial translocation and residual immune activation in HIV-infected, ART suppressed opioid use disorder patents initiating medication-assisted treatment
mu-阿片受体结合对 HIV 感染者、ART 抑制的阿片类药物使用障碍患者微生物易位和残余免疫激活的影响,开始药物辅助治疗
基本信息
- 批准号:10654008
- 负责人:
- 金额:$ 162.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-01 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:Acquired Immunodeficiency SyndromeAcuteAdherenceAgonistAwardBehavioralCaringCellsCharacteristicsChronicCirculationCitiesClinicClinicalClinical ResearchClinical TrialsCounselingCountryDNADataExposure toFranceFutureGenetic TranscriptionGovernmentHIVHIV InfectionsHIV-1HIV/AIDSHarm ReductionHealthHepatitisHeroinHeroin UsersHigh PrevalenceImmunologicsImmunotherapyIndividualIndustryInflammationInfrastructureInjecting drug userInterdisciplinary StudyInternationalIntravenousKineticsLegal patentLinkMaintenanceMeasuresMethadoneMorbidity - disease rateNaltrexoneOpiate AddictionOpioidOpioid ReceptorOralOutcomeOutcome StudyPatientsPennsylvaniaPeripheral Blood Mononuclear CellPersonsPharmaceutical PreparationsPhiladelphiaRNARandomizedRecoveryResearchResidual stateRiskSiteTestingThe Wistar InstituteTimeUniversitiesVietnamVietnameseViraladdictionantagonistantiretroviral therapyarmclinical careclinically relevantcohortimmune activationimmune reconstitutionindustry partnerintervention effectintervention programmedication-assisted treatmentmembermethadone treatmentmicrobialmortalitymu opioid receptorsopioid useopioid use disorderopioid userprevention serviceprimary endpointprogramsrandomized trialretention ratesystemic inflammatory responsetreatment programtreatment servicestrial comparingviral DNAviral RNA
项目摘要
PROJECT SUMMARY
HIV infection, as well as exposure to opioids including intravenous heroin, are associated with systemic immune
activation including increased microbial translocation from the gut. The overall objective of this study is to
provide clinical evidence on the detrimental link between kinetics and characteristics of immune reconstitution
(microbial translocation, residual immune activation, retained HIV expression) in HIV-1 infected people who
inject drugs (PWIDs) and sustain interaction with the μ-opioid receptor (MOR) while on antiretroviral therapy
(ART). Defining the impact of continued MOR engagement after ART initiation is of relevance to addiction
treatment as maintenance-assisted treatment options include using a MOR agonist (methadone, MET) or a
MOR antagonist (long-acting naltrexone, XR-NTX). Notably, the effect of oral MET, which is widely used in
maintenance treatment, on ART-mediated immune reconstitution is unknown. Based on preliminary data
showing higher microbial translocation, immune activation, and active HIV transcription in ART-suppressed
PWID on MET over XR-NTR, we will test the primary hypothesis that chronic engagement of mu-opioid receptor
by a full MOR agonist (MET) while on ART will result in reduced rates and magnitude of microbial translocation,
with sustained immune activation and inflammation associated with increased levels of persistent HIV (i.e.,
integrated HIV DNA, cell-associated HIV RNA) when compared to a full MOR antagonist (XR-NTX) in spite of
viral suppression. Specifically, we will test these hypotheses in the following specific aims: Specific Aim 1.
Defining the impact of long-term MOR stimulation (MET) or blockage (XR-NTX) on the kinetics and extent of
immune reconstitution in PWID initiating ART. To this end, we will also compare 48 week changes on residual
immune activation, microbial translocation, and systemic inflammation in a cohort of PWID with chronic HIV
infection initiating ART, randomized 1:1 to either MET or XR-NTX. sCD14 level change after ART will serve as
the primary end-point variable. Specific Aim 2. Defining the clinical and virologic correlates of 48 week
treatment with MOR agonists (MET) and antagonists (XR-NTX), by studying effect of the intervention on CD4,
adherence to ART, acceptability of MAT, as well as retention in care. Changes in persistent HIV measures will
also be measured (i.e., persistence of viral RNA and DNA species in PBMC, etc.). Given the high prevalence
of HIV-infected heroin users starting ART and opioid addition therapy, Vietnam is an ideal setting to complete
the proposed study to provide generalizable proof-of-concept data in support of future long-term clinical
outcome studies. This study represents an international multi-disciplinary collaboration between the Vietnam
Ministry of Health, the Vietnam Administration of HIV/AIDS Control, the Provincial AIDS Committee, the
University of Pennsylvania, Expertise France (a French-led initiative to expand access to HIV/ Hepatitis
prevention and treatment services), the Pasteur Institute, Alkermes (industry partner), and The Wistar Institute.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('DAVID S METZGER', 18)}}的其他基金
Effects of mu-opiate receptor engagement on microbial translocation and residual immune activation in HIV-infected, ART suppressed opioid use disorder patents initiating medication-assisted treatment
mu-阿片受体结合对 HIV 感染者、ART 抑制的阿片类药物使用障碍患者微生物易位和残余免疫激活的影响,开始药物辅助治疗
- 批准号:
10197865 - 财政年份:2019
- 资助金额:
$ 162.12万 - 项目类别:
Effects of mu-opiate receptor engagement on microbial translocation and residual immune activation in HIV-infected, ART suppressed opioid use disorder patents initiating medication-assisted treatment
mu-阿片受体结合对 HIV 感染者、ART 抑制的阿片类药物使用障碍患者微生物易位和残余免疫激活的影响,开始药物辅助治疗
- 批准号:
10436808 - 财政年份:2019
- 资助金额:
$ 162.12万 - 项目类别:
Effects of mu-opiate receptor engagement on microbial translocation and residual immune activation in HIV-infected, ART suppressed opioid use disorder patents initiating medication-assisted treatment
mu-阿片受体结合对 HIV 感染者、ART 抑制的阿片类药物使用障碍患者微生物易位和残余免疫激活的影响,开始药物辅助治疗
- 批准号:
10004224 - 财政年份:2019
- 资助金额:
$ 162.12万 - 项目类别:
Rapid initiation of buprenorphine/naloxone to optimize MAT utilization in Philadelphia
快速启动丁丙诺啡/纳洛酮以优化费城 MAT 的利用
- 批准号:
9896726 - 财政年份:2018
- 资助金额:
$ 162.12万 - 项目类别:
Efficacy of Drug-HIV counseling among IDU at Methadone clinics in Jakarta
雅加达美沙酮诊所注射吸毒者药物艾滋病毒咨询的效果
- 批准号:
7835556 - 财政年份:2009
- 资助金额:
$ 162.12万 - 项目类别:
Efficacy of Drug-HIV counseling among IDU at Methadone clinics in Jakarta
雅加达美沙酮诊所注射吸毒者药物艾滋病毒咨询的效果
- 批准号:
7687184 - 财政年份:2009
- 资助金额:
$ 162.12万 - 项目类别:
Efficacy of Drug-HIV counseling among IDU at Methadone clinics in Jakarta
雅加达美沙酮诊所注射吸毒者药物艾滋病毒咨询的效果
- 批准号:
8261981 - 财政年份:2009
- 资助金额:
$ 162.12万 - 项目类别:
Efficacy of Drug-HIV counseling among IDU at Methadone clinics in Jakarta
雅加达美沙酮诊所注射吸毒者药物艾滋病毒咨询的效果
- 批准号:
8085908 - 财政年份:2009
- 资助金额:
$ 162.12万 - 项目类别:
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