Point-of-care and Near Real-time Testing for Antiretroviral Adherence Monitoring to HIV Treatment and Prevention

Drain, Paul K.; Bardon, Ashley; Simoni, Jane M.; Cressey, Tim R.; Anderson, Pete; Sevenler, Derin; Olanrewaju, Ayokunle; Gandhi, Monica; Celum, Connie

doi:10.1007/s11904-020-00512-3

Cited by 24 publications

(40 citation statements)

References 102 publications

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“…To achieve this goal, novel intervention packages and adherence monitoring strategies are needed to objectively assess ART adherence, identify discrepancies in ART adherence and viral suppression, and motivate optimal adherence patterns among PLHIV. 27 Existing strategies for ART adherence monitoring may be ineffective in identifying adherence challenges or drug resistance before virological failure or disengagement from care occurs. 27 Therefore, implementing effective adherence and retention interventions, including enhanced adherence counselling for those who are at risk of developing viraemia at the point of care, is vital to extend the durability of first-line treatment.…”

Section: Methodsmentioning

confidence: 99%

“… 29 POC tests for routine monitoring of ART adherence and VL may be helpful in promoting good adherence practices and managing care for PLHIV in real time. 27 We seek to evaluate the effects of integrating two POC tests—a TFV adherence test and a VL test—into care for PLHIV at a large, public clinic in South Africa. Our primary objective is to determine if an integrated model for HIV monitoring, including routine POC TFV adherence testing and POC HIV VL monitoring, improves ART adherence, viral suppression and retention in care.…”

Section: Introductionmentioning

confidence: 99%

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Simplifying TREAtment and Monitoring for HIV (STREAM HIV): protocol for a randomised controlled trial of point-of-care urine tenofovir and viral load testing to improve HIV outcomes

et al. 2021

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IntroductionSubstantial improvements in viral suppression among people living with HIV (PLHIV) are needed to end the HIV epidemic, requiring extensive scale-up of low-cost HIV monitoring services. Point-of-care (POC) tests for monitoring antiretroviral therapy (ART) adherence and viral load (VL) may be efficient and effective tools for real-time clinical decision making. We aim to evaluate the effects of a combined intervention of POC ART adherence and VL testing compared with standard-of-care on ART adherence, viral suppression and retention at 6 and 18 months post-ART initiation among PLHIV.Methods and analysisSimplifying TREAtment and Monitoring for HIV (STREAM HIV) is a two-arm, open-label, randomised controlled superiority trial of POC urine tenofovir (POC TFV) and VL monitoring in PLHIV. We aim to enrol 540 PLHIV initiating a first-line ART regimen at a public HIV clinic in South Africa. Participants will be randomised 1:1 to the intervention or control arm. Intervention arm participants will receive monthly POC TFV testing for the first 5 months and POC VL testing at months 6 and 12. Intervention arm participants will also receive reflex POC TFV testing if viraemic and reflex HIV drug resistance testing for those with viraemia and detectable TFV. Control arm participants will receive standard-of-care, including laboratory-based VL testing at months 6 and 12. Primary outcomes include ART adherence (TFV-diphosphate concentration) at 6 months and viral suppression and retention at 18 months. Secondary outcomes include viral suppression and retention at 6 months, TFV-diphosphate concentration at 18 months, cost and cost-effectiveness of the intervention and acceptability of the intervention among PLHIV and healthcare workers.Ethics and disseminationSTREAM HIV has received ethical approval from the University of Washington Institutional Review Board (STUDY00007544), University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC/00000833/2019) and Division of AIDS Regulatory Support Center (38509). Findings will be disseminated at international conferences and in peer-reviewed journals.Trial registration numberNCT04341779.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Simplifying TREAtment and Monitoring for HIV (STREAM HIV): protocol for a randomised controlled trial of point-of-care urine tenofovir and viral load testing to improve HIV outcomes

et al. 2021

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“…Real-time, objective measures of adherence for PrEP are essential to assess how and when people are taking medication, and to accelerate a clinical and/or other supportive response for those with inadequate adherence. 20 , 21 Quantifying and monitoring adherence to PrEP can identify those at risk of becoming lost to follow-up and therefore at greater risk of HIV infection, 22 those in need of additional layers of support to overcome barriers to PrEP (impending health insurance loss, harm reduction tools, logistical support such as tokens), and individuals who need enhanced adherence support (more frequent visits, pill boxes, smart pill bottles, etc.). Indeed, metrics of PrEP adherence were strongly associated with future loss to follow-up in a US demonstration project study.…”

Section: Introductionmentioning

confidence: 99%

Real-Time Monitoring and Point-of-Care Testing: A Review of the Current Landscape of PrEP Adherence Monitoring

Hannaford¹,

Arens²,

Koenig³

2021

PPA

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Background Despite pre-exposure prophylaxis (PrEP) being highly effective at preventing HIV, HIV infections among individuals prescribed PrEP continue to occur. The vast majority of these new infections occur among individuals with sub-optimal adherence. One factor that is likely to decrease HIV incidence among PrEP users is a real-time, objective measurement of adherence. Monitoring adherence to PrEP can identify those at risk of becoming lost to follow-up and therefore at greater risk of HIV infection, those in need of additional layers of support to overcome barriers to PrEP, and individuals who need enhanced adherence support. Objective This paper reviews subjective and objective methods for monitoring PrEP including self-report, drug level monitoring (including serum, plasma, peripheral blood mononuclear cells [PBMC], red blood cell dried blood spots [DBS], hair, and urine) and by measuring participant interaction with the study drug (pill counts, medication event monitoring systems [MEMS] caps). Clinical Use A multitude of methods exist for monitoring and supporting adherence. Objective monitoring using DBS and urine will provide a more accurate picture of adherence compared to subjective and non-biomarker objective methods. Preliminary data show that detection of non-adherence using biomarkers, followed by augmented adherence support and counseling, is associated with improved adherence, although more research is needed. PrEP providers will need knowledge of and access to these various strategies, which will require investment and resource allocation from clinics and other PrEP care sites to provide these tools.

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“…In several PrEP trials and implementation studies, PrEP clients had difficulties maintaining adequate adherence and persistence, and monitoring their PrEP use was challenging [ 4 , 6 , 7 ]. Various indirect and subjective measures have been used to measure adherence [ 8 – 11 ], while quantifying concentrations of HIV drugs in clinical samples may provide more objective information for adherence measurement [ 8 , 12 – 14 ].…”

Section: Introductionmentioning

confidence: 99%

Pilot evaluation of an enzymatic assay for rapid measurement of antiretroviral drug concentrations

Olanrewaju

Sullivan

Bardon

et al. 2021

Virol J

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Objective Maintaining adequate drug adherence is crucial to ensure the HIV prevention benefits of pre-exposure prophylaxis (PrEP). We developed an enzymatic assay for rapidly measuring tenofovir-diphosphate (TFV-DP) concentrations—a metabolite that indicates long-term PrEP adherence. Setting The study was conducted at the Madison HIV Clinic at Harborview Medical Center in Seattle. Methods We enrolled adults receiving standard oral PrEP, and individuals not receiving any antiretrovirals. We measured TFV-DP concentrations in diluted whole blood using our novel REverSe TRanscrIptase Chain Termination (RESTRICT) assay, based on inhibition of HIV reverse transcriptase (RT) enzyme. Blood samples were diluted in water, DNA templates, nucleotides, RT, and intercalating dye added, and results measured with a fluorescence reader—stronger fluorescence indicated higher RT activity. We compared RESTRICT assay results to TFV-DP concentrations from matched dried blood spot samples measured by liquid chromatography tandem mass spectrometry (LC–MS/MS) using ≥ 700 fmol/punch TFV-DP as a threshold for adequate adherence (≥ 4 doses/week). Results Among 18 adults enrolled, 4 of 7 participants receiving PrEP had TFV-DP levels ≥ 700 fmol/punch by LC–MS/MS. RESTRICT fluorescence correlated with LC–MS/MS measurements (r = − 0.845, p < 0.0001). Median fluorescence was 93.3 (95% confidence interval [CI] 90.9 to 114) for samples < 700 fmol/punch and 54.4 (CI 38.0 to 72.0) for samples ≥ 700 fmol/punch. When calibrated to an a priori defined threshold of 82.7, RESTRICT distinguished both groups with 100% sensitivity and 92.9% specificity. Conclusions This novel enzymatic assay for measuring HIV reverse transcriptase activity may be suitable for distinguishing TFV-DP concentrations in blood that correspond to protective PrEP adherence.

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Point-of-care and Near Real-time Testing for Antiretroviral Adherence Monitoring to HIV Treatment and Prevention

Cited by 24 publications

References 102 publications

Simplifying TREAtment and Monitoring for HIV (STREAM HIV): protocol for a randomised controlled trial of point-of-care urine tenofovir and viral load testing to improve HIV outcomes

Simplifying TREAtment and Monitoring for HIV (STREAM HIV): protocol for a randomised controlled trial of point-of-care urine tenofovir and viral load testing to improve HIV outcomes

Real-Time Monitoring and Point-of-Care Testing: A Review of the Current Landscape of PrEP Adherence Monitoring

Pilot evaluation of an enzymatic assay for rapid measurement of antiretroviral drug concentrations

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