Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes

Mave, Vidya; Kadam, Dileep; Gaikwad, Sanjay; Kinikar, Aarti; Aguilar, David; Chavan, Amol; Paradkar, Mandar; Yogendra, Singh; Bharadwaj, Renu; Kagal, Anju; Suryavanshi, Nishi; Golub, Jonathan E.; Kulkarni, Vandana; Dooley, KE; Gupta, Amita; Bacchetti, Peter; Gerona, Roy; Gupte, Nikhil; Gandhi, Monica

doi:10.5588/ijtld.20.0574

Cited by 9 publications

(14 citation statements)

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“…Acting upon such delays may be of benefit in India, where PWT face challenges in reaching clinics to collect their medication refills [ 4 ]. Measuring drug metabolites in other specimens such as hair may also be valuable, although these assays may be more costly than urine testing [ 40 ]. In addition, given that ~11% of people with TB in India without a prior treatment history (ie, “new cases”) have isoniazid-monoresistant disease [ 41 ], point-of-care drug metabolite testing approaches need to be developed for other TB drugs.…”

Section: Discussionmentioning

confidence: 99%

Measuring tuberculosis medication adherence: a comparison of multiple approaches in relation to urine isoniazid metabolite testing within a cohort study in India

Subbaraman

Thomas

Kumar

et al. 2021

Open Forum Infectious Diseases

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Background Nonadherence to tuberculosis medications is associated with poor outcomes. However, measuring adherence in practice is challenging. In this study, we evaluated the accuracy of multiple tuberculosis adherence measures. Methods We enrolled adult Indians with drug-susceptible tuberculosis who were monitored using 99DOTS, a cellphone-based technology. During an unannounced home visit with each participant, we assessed adherence using a pill estimate, four-day dose recall, a last missed dose question, and urine isoniazid metabolite testing. We estimated the area under the receiver operating characteristic curve (AUC) for each alternate measure in comparison to urine testing. 99DOTS data were analyzed using patient-reported doses alone and patient- and provider-reported doses, the latter reflecting how 99DOTS is implemented in practice. We assessed each measure’s operating characteristics, with particular interest in specificity—i.e., the percentage of participants detected as being nonadherent by each alternate measure, among those who were nonadherent by urine testing. Results Compared to urine testing, alternate measures had the following characteristics: 99DOTS patient-reported doses alone (AUC 0.65, specificity 70%, 95%CI:58—81%), 99DOTS patient- and provider-reported doses (AUC 0.61, specificity 33%, 95%CI: 22—45%), pill estimate (AUC 0.55, specificity 21%, 95%CI:12—32%), four-day recall (AUC 0.60, specificity 23%, 95%CI: 14—34%), and last missed dose question (AUC 0.65, specificity 52%, 95%CI:40—63%). Conclusions Alternate measures missed detecting at least 30% of people who were nonadherent by urine testing. The last missed dose question performed similarly to 99DOTS using patient-reported doses alone. Tuberculosis programs should evaluate the feasibility of integrating more accurate, objective measures, such as urine testing, into routine care.

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Section: Discussionmentioning

confidence: 99%

Measuring tuberculosis medication adherence: a comparison of multiple approaches in relation to urine isoniazid metabolite testing within a cohort study in India

Subbaraman

Thomas

Kumar

et al. 2021

Open Forum Infectious Diseases

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“…Once there, we (R.A. and A.R.R.) extracted and quantified INH and acetyl INH (a metabolite that is dependent on host acetylation status) in the hair samples using the isotope dilution method (internal standards: INH-d4 and acetyl-INH-d4) by LC-MS/MS [ 22 , 23 ].…”

Section: Methodsmentioning

confidence: 99%

Agreement Between Measures of Adherence to Isoniazid Preventive Therapy Among People With HIV in Uganda

Forman

Lodi

Fatch

et al. 2022

Open Forum Infectious Diseases

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Background Isoniazid (INH) preventative therapy is recommended for people with HIV (PWH) in resource-constrained settings. Valid measures are needed to assess adherence. We aimed to examine agreement between measures overall and by level of social desirability. Methods PWH with latent TB were recruited in Mbarara, Uganda. Past 30-day adherence was measured by the number of days with pill bottle openings using a Medication Event Monitoring System (MEMS) and self-reported number of days pills taken. INH concentration (INH plus acetyl INH and their ratio) in hair samples was measured. We used Bland-Altman plots to examine agreement between adherence measures, and calculated the area under the receiver operator curve (ARUC) to determine if INH hair concentration predicted optimal MEMS-measured adherence (≥90%). Results 301 participants enrolled; 92% were virologically suppressed, and adherence was high. Median [IQR] number of pill bottle openings in 30 days were 28 [24, 30] compared to 30 [28, 30] via self-report. INH concentration was 36.2 [17.2, 62.4], and the INH:acetyl ratio was 2.43 [0.99, 3.92]. Agreement between self-reported and MEMS adherence was greater at more optimal adherence levels. INH:acetyl INH ratio was not predictive of optimal adherence according to MEMS (ARUC 0.62 (95% CI: 0.52, 0.72)) in a subset (n = 161). Conclusions Lower MEMS adherence levels compared to self-report suggest the need for objective adherence measures. Biologic measures have potential, although in this study INH concentration was not predictive of MEMS measured adherence. More data are needed to assess their accuracy.

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“…Our survey showed that progress in TDM is being made, with half of the survey participants using TDM. Cheaper and easy to use assays [9][10][11], clinical guidelines [2][3][4] and laboratory quality control standards [12] are all increasing in availability. However, the main challenge is a lack of widespread information about TDM, with progress being recognised by participants who look towards guidelines and research when performing TDM.…”

Section: Https://isgd/tdmsurveymentioning

confidence: 99%

Practices of therapeutic drug monitoring in tuberculosis: an international survey

et al. 2022

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Measuring TB drug levels in the hair in adults and children to monitor drug exposure and outcomes

Cited by 9 publications

References 0 publications

Measuring tuberculosis medication adherence: a comparison of multiple approaches in relation to urine isoniazid metabolite testing within a cohort study in India

Measuring tuberculosis medication adherence: a comparison of multiple approaches in relation to urine isoniazid metabolite testing within a cohort study in India

Agreement Between Measures of Adherence to Isoniazid Preventive Therapy Among People With HIV in Uganda

Practices of therapeutic drug monitoring in tuberculosis: an international survey

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