Actionable Adherence Monitoring: Technological Methods to Monitor and Support Adherence to Antiretroviral Therapy

Bell, Kate M.; Haberer, Jessica

doi:10.1007/s11904-018-0413-0

Cited by 19 publications

(25 citation statements)

References 57 publications

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“…The RESTRICT assay could be used to fill the gap of rapid long-term adherence measurement to promote more honest conversations about PrEP use and enable improved PrEP counselling. [ 7 , 33 , 34 ].…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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show abstract

“…The RESTRICT assay could be used to ll the gap of rapid long-term adherence measurement to promote more honest conversations about PrEP use and enable improved PrEP counselling. (7,33,34) List Of Abbreviations…”

Section: Discussionmentioning

confidence: 99%

Pilot Evaluation of an Enzymatic Assay for Rapid Measurement of Antiretroviral Drug Concentrations

Olanrewaju

Sullivan

Bardon

et al. 2021

Preprint

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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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“…To increase efficiency, electronic pharmacy refills that interface with prescribing clinics would streamline data collection, and can even enable clinical alerts to providers when a patient has missed picking up a prescription. 31 The most significant limitation to monitoring pharmacy refills is the assumption that individuals are taking all doses that they pick up, and this method likely overestimates adherence when compared to other objective measures. 32…”

Section: Objective Tools For Monitoring Prep Adherencementioning

confidence: 99%

“…Electronic adherence monitors (EAMs) are devices that enable day-to-day adherence monitoring and have been used for ART 31 and tuberculosis treatment 35 but have yet to be fully explored for PrEP. The most widely known is the Medication Event Monitoring System (MEMS), a medication bottle that records a time and date stamp when the bottle is opened and allows for the transfer of this information to a computer via USB.…”

Section: Objective Tools For Monitoring Prep Adherencementioning

confidence: 99%

“…Messages can be sent to the prescribed individual, but can also be sent to other individuals (eg friends or providers) who can act as a support group. 31 This technology, among others, was shown to improve ART adherence in a cohort of rural Ugandans living with HIV. 36 The automatic reminder strategy may be helpful for daily use of PrEP, although with on-demand use it may be less relevant.…”

Section: Objective Tools For Monitoring Prep Adherencementioning

confidence: 99%

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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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Actionable Adherence Monitoring: Technological Methods to Monitor and Support Adherence to Antiretroviral Therapy

Cited by 19 publications

References 57 publications

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

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

Pilot Evaluation of an Enzymatic Assay for Rapid Measurement of Antiretroviral Drug Concentrations

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

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