Strong Correlation Between Concentrations of Antiretrovirals in Home-Collected and Study-Collected Hair Samples: Implications for Adherence Monitoring

Saberi, Parya; Neilands, Torsten B.; Ming, Kristin; Johnson, Mallory O.; Kuncze, Karen; Koss, Catherine A.; Gandhi, Monica

doi:10.1097/qai.0000000000001492

Cited by 15 publications

(16 citation statements)

References 12 publications

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“…Hair collection has some feasibility advantages in the field since no phlebotomy or cold chain is required and hair samples can be self-collected. [17] In this substudy of the Demo Project, we demonstrated that DBS and hair concentrations of PrEP drugs were highly concordant (84%) and that high-risk behavior (condomless receptive anal sex and amphetamine use), and a more stable living situation were associated with higher levels of adherence to PrEP drugs as adjudicated by hair levels. Furthermore, we found a greater decline in renal function (and greater increases in creatinine) from baseline with higher hair levels of PrEP drugs.…”

Section: Discussionmentioning

confidence: 94%

“…In other studies where hair collection is incorporated early in the protocol and the field staff trained that hair can be collected from very short hair, takes very little time, and does not disrupt hair styles, acceptability has been very high. [32–34] New data that self-collected hair yields similar concentration data to hair collected in the field [17] may enhance the acceptability of this measure. Of importance in this study was that only 1% of participants were concerned about providing a sample that could reveal their adherence level and other studies have suggested that provision of drug levels could improve subsequent drug-taking.…”

Section: Discussionmentioning

confidence: 99%

“…[10] Concentrations of TFV and/or FTC (or their metabolites) in dried blood spots (DBS) [11] and hair samples [12] measure longer-term adherence and exposure, are highly correlated, [13] are associated with both efficacy [14] and toxicities of PrEP, [15, 16] and have therefore been increasingly incorporated as adherence metrics into PrEP programs during scale-up. Since hair can be collected (even at home [17] ) and stored at room temperature without biohazardous precautions, providing feasibility in the field, we sought to compare its utility as an alternative adherence measure to DBS in a large PrEP study.…”

Section: Introductionmentioning

confidence: 99%

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Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen

Gandhi¹,

Murnane

Bacchetti

et al. 2017

Aids

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Objective The U.S. PrEP Demonstration Project (Demo) evaluated men-who-have-sex-with-men on pre-exposure prophylaxis (PrEP) post-marketing and found low seroconversion rates. The objective of this study is to examine hair levels as an adherence measure to PrEP. Design Using an “opt-in” design, participants of PrEP Demo were invited to enroll into a substudy where hair was collected quarterly. Methods Tenofovir concentrations were measured in hair by liquid-chromatography/tandem-mass-spectrometry. Hair levels consistent with ≥4 doses per week (protective in other studies) defined adequate adherence. Mixed effects multivariate logistic regression models examined factors associated with ≥4 doses/week. Separate mixed effects models evaluated the relationship between hair PrEP levels and changes in creatinine clearance (CrCl) over time. Results Overall, 58% of Demo participants enrolled into this opt-in study; reasons for non-participation included insufficient hair (61%) and concerns about hairstyle (27%). Hair and DBS levels consistent with ≥4 doses/week were highly concordant (84%). Hair levels showed adequate adherence in 87% of 875 person-visits (among 280 participants). Factors associated with adequate adherence in multivariate models were amphetamine use (aOR 2.59 (0.97–6.9, p 0.06), condomless receptive anal sex (aOR 2.28 (1.19–4.40, p 0.01), and stable housing (aOR 2.63 (1.03–6.67), p 0.04). Hair levels of tenofovir showed a monotonic relationship with decline in CrCl (p 0.01 for trend). Conclusions In this substudy of the PrEP Demonstration Project, hair and DBS levels were highly concordant and hair concentrations demonstrated adequate adherence 87% of the time, with stable housing and high-risk behavior associated with higher adherence. Daily PrEP drug-taking is associated with modest declines in CrCl.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen

Gandhi¹,

Murnane

Bacchetti

et al. 2017

Aids

Self Cite

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“…To date, multiple different liquid chromatography-based assays to quantify these drugs have been developed[76–78] and utilized as adherence measures in HIV treatment and prevention studies. These methods usually require 50–100 strands of hair that is obtained as close as possible to the scalp[79], which can also be obtained through self-collection, with good correlation with traditional hair collection procedures[80]. In HIV treatment, hair concentrations have been demonstrated to be strong predictors of virologic success in large and diverse prospective clinical cohorts of PLWH, performing better than other traditional adherence measures as predictors of treatment outcomes[79, 81–85].…”

Section: New Pharmacologic Measures That Quantify Cumulative Drug Expmentioning

confidence: 99%

Adherence Measurements in HIV: New Advancements in Pharmacologic Methods and Real-Time Monitoring

2018

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Antiretroviral drug concentrations in hair and dried blood spots are two novel pharmacological measures of cumulative drug adherence and exposure that have been recently evaluated in HIV treatment and pre-exposure prophylaxis. Real-time adherence monitoring using electronic devices has also proven highly informative, feasible, and well accepted, offering the possibility for an immediate intervention when non-adherence is detected. Both approaches offer considerable advantages over traditional adherence measures in predicting efficacy. New methods to objectively monitor adherence in real-time and over long time periods have been developed. Further research is required to better understand how these measures can optimize adherence and, ultimately, improve clinical outcomes in HIV treatment and prevention.

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“…One way to objectively monitor adherence is to analyze antiretroviral (ARV) drug concentrations in different biomatrices. Our group has developed expertise in the measurement of ARV levels in hair to assess adherence and its exposure in the context of both HIV prevention and treatment …”

Section: Introductionmentioning

confidence: 99%

Development and validation of an assay to analyze atazanavir in human hair via liquid chromatography/tandem mass spectrometry

Phung

Kuncze

Okochi

et al. 2018

Rapid Comm Mass Spectrometry

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Rationale Assays to quantify antiretrovirals in hair samples are increasingly used to monitor adherence and exposure in both HIV prevention and treatment studies. Atazanavir (ATV) is a protease inhibitor used in combination antiretroviral therapy (ART). We developed and validated a liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based method to quantify ATV in human hair, per the NIH Division of AIDS Clinical Pharmacology Quality Assurance (CPQA) program and the FDA bioanalytical method validation guidelines. Methods ATV was extracted from hair using optimized methods and the extracts were injected onto a BDS C-18 column (5 μm, 4.6 × 100 mm), followed by isocratic elution via a mobile phase composed of 55% acetonitrile, 45% water, 0.15% acetic acid, and 4 mM ammonium acetate, at a flow rate of 0.8 mL/min prior to analysis by MS/MS. Levels were quantified using positive electrospray ionization by multiple reaction monitoring (MRM) for the transitions MH+ m/z 705.3 to m/z 168.0 and MH+ m/z 710.2 to m/z 168.0 for ATV and ATV-d5 (internal standard), respectively. Results Our assay demonstrated a linear standard curve (r = 0.99) over the concentration range of 0.0500 ng ATV/mg hair to 20.0 ng/mg hair. The inter- and intraday accuracy of ATV quality control (QC) samples was −1.33 to 4.00% and precision (% coefficient of variation (%CV)) was 1.75 to 6.31%. The %CV for ATV levels in hair samples from highly adherent patients (incurred samples) was less than 10%. No significant endogenous peaks or crosstalk were observed in the specificity test with other HIV drugs. The overall extraction efficiency of ATV from incurred hair samples was greater than 95%. Conclusions This highly sensitive, highly specific and validated assay can be considered for therapeutic drug monitoring for HIV-infected patients on ATV-based ART.

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Strong Correlation Between Concentrations of Antiretrovirals in Home-Collected and Study-Collected Hair Samples: Implications for Adherence Monitoring

Cited by 15 publications

References 12 publications

Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen

Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen

Adherence Measurements in HIV: New Advancements in Pharmacologic Methods and Real-Time Monitoring

Development and validation of an assay to analyze atazanavir in human hair via liquid chromatography/tandem mass spectrometry

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