Understanding Nonadherence to Tuberculosis Medications in India Using Urine Drug Metabolite Testing: A Cohort Study.

BACKGROUND: Poor adherence to tuberculosis (TB) treatment is associated with disease recurrence and death. Little research has been conducted in India to understand TB medication nonadherence. METHODS: We enrolled adult drug-susceptible TB patients, approximately half of whom were people with human immunodeficiency virus (PWH), in Chennai, Vellore, and Mumbai. We conducted a single unannounced home visit to administer a survey assessing reasons for nonadherence and collect a urine sample that was tested for isoniazid content. We described patient-reported reasons for nonadherence and identified factors associated with nonadherence (ie, negative urine test) using multivariable logistic regression. We also assessed the association between nonadherence and treatment outcomes. RESULTS: Of 650 participants in the cohort, 77 (11.8%) had a negative urine test. Nonadherence was independently associated with daily wage labor (adjusted odds ratio [aOR], 2.7; confidence interval [CI], 1.1-6.5; P = .03), the late continuation treatment phase (aOR, 2.0; CI, 1.1-3.9; P = .03), smear-positive pulmonary disease (aOR, 2.1; CI, 1.1-3.9; P = .03), alcohol use (aOR, 2.5; CI, 1.2-5.2; P = .01), and spending ≥30 minutes collecting medication refills (aOR, 6.6; CI, 1.5-29.5; P = .01). People with HIV reported greater barriers to collecting medications than non-PWH. Among 167 patients reporting missing doses, reported reasons included traveling from home, forgetting, feeling depressed, and running out of pills. The odds of unfavorable treatment outcomes were 4.0 (CI, 2.1-7.6) times higher among patients with nonadherence (P < .0001). CONCLUSION: Addressing structural and psychosocial barriers will be critical to improve TB treatment adherence in India. Urine isoniazid testing may help identify nonadherent patients to facilitate early intervention during treatment.

Acceptability of the Medication Event Reminder Monitor for Promoting Adherence to Multidrug-Resistant Tuberculosis Therapy in Two Indian Cities: Qualitative Study of Patients and Health Care Providers.

BACKGROUND: Patients with multidrug-resistant tuberculosis (MDR-TB) face challenges adhering to medications, given that treatment is prolonged and has a high rate of adverse effects. The Medication Event Reminder Monitor (MERM) is a digital pillbox that provides pill-taking reminders and facilitates the remote monitoring of medication adherence. OBJECTIVE: This study aims to assess the MERM's acceptability to patients and health care providers (HCPs) during pilot implementation in India's public sector MDR-TB program. METHODS: From October 2017 to September 2018, we conducted qualitative interviews with patients who were undergoing MDR-TB therapy and were being monitored with the MERM and HCPs in the government program in Chennai and Mumbai. Interview transcripts were independently coded by 2 researchers and analyzed to identify the emergent themes. We organized findings by using the Unified Theory of Acceptance and Use of Technology (UTAUT), which outlines 4 constructs that predict technology acceptance-performance expectancy, effort expectancy, social influence, and facilitating conditions. RESULTS: We interviewed 65 patients with MDR-TB and 10 HCPs. In patient interviews, greater acceptance of the MERM was related to perceptions that the audible and visual reminders improved medication adherence and that remote monitoring reduced the frequency of clinic visits (performance expectancy), that the device's organization and labeling of medications made it easier to take them correctly (effort expectancy), that the device facilitated positive family involvement in the patient's care (social influences), and that remote monitoring made patients feel more cared for by the health system (facilitating conditions). Lower patient acceptance was related to problems with the durability of the MERM's cardboard construction and difficulties with portability and storage because of its large size (effort expectancy), concerns regarding stigma and the disclosure of patients' MDR-TB diagnoses (social influences), and the incorrect understanding of the MERM because of suboptimal counseling (facilitating conditions). In their interviews, HCPs reported that MERM implementation resulted in fewer in-person interactions with patients and thus allowed HCPs to dedicate more time to other tasks, which improved job satisfaction. CONCLUSIONS: Several features of the MERM support its acceptability among patients with MDR-TB and HCPs, and some barriers to patient use could be addressed by improving the design of the device. However, some barriers, such as disease-related stigma, are more difficult to modify and may limit use of the MERM among some patients with MDR-TB. Further research is needed to assess the accuracy of MERM for measuring adherence, its effectiveness for improving treatment outcomes, and patients' sustained use of the device in larger scale implementation.

Measuring Tuberculosis Medication Adherence: A Comparison of Multiple Approaches in Relation to Urine Isoniazid Metabolite Testing Within a Cohort Study in India.

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, 4-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-that is, the percentage of participants detected as being nonadherent by each alternate measure, among those who were nonadherent by urine testing. Results: Compared with urine testing, alternate measures had the following characteristics: 99DOTS patient-reported doses alone (area under the curve [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%), 4-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.

Explaining Differences in the Acceptability of 99DOTS, a Cell Phone-Based Strategy for Monitoring Adherence to Tuberculosis Medications: Qualitative Study of Patients and Health Care Providers.

BACKGROUND: 99DOTS is a cell phone-based strategy for monitoring tuberculosis (TB) medication adherence that has been rolled out to more than 150,000 patients in India's public health sector. A considerable proportion of patients stop using 99DOTS during therapy. OBJECTIVE: This study aims to understand reasons for variability in the acceptance and use of 99DOTS by TB patients and health care providers (HCPs). METHODS: We conducted qualitative interviews with individuals taking TB therapy in the government program in Chennai and Vellore (HIV-coinfected patients) and Mumbai (HIV-uninfected patients) across intensive and continuation treatment phases. We conducted interviews with HCPs who provide TB care, all of whom were involved in implementing 99DOTS. Interviews were transcribed, coded using a deductive approach, and analyzed with Dedoose 8.0.35 software (SocioCultural Research Consultants, LLC). The findings of the study were interpreted using the unified theory of acceptance and use of technology, which highlights 4 constructs associated with technology acceptance: performance expectancy, effort expectancy, social influences, and facilitating conditions. RESULTS: We conducted 62 interviews with patients with TB, of whom 30 (48%) were HIV coinfected, and 31 interviews with HCPs. Acceptance of 99DOTS by patients was variable. Greater patient acceptance was related to perceptions of improved patient-HCP relationships from increased phone communication, TB pill-taking habit formation due to SMS text messaging reminders, and reduced need to visit health facilities (performance expectancy); improved family involvement in TB care (social influences); and from 99DOTS leading HCPs to engage positively in patients' care through increased outreach (facilitating conditions). Lower patient acceptance was related to perceptions of reduced face-to-face contact with HCPs (performance expectancy); problems with cell phone access, literacy, cellular signal, or technology fatigue (effort expectancy); high TB- and HIV-related stigma within the family (social influences); and poor counseling in 99DOTS by HCPs or perceptions that HCPs were not acting upon adherence data (facilitating conditions). Acceptance of 99DOTS by HCPs was generally high and related to perceptions that the 99DOTS adherence dashboard and patient-related SMS text messaging alerts improve quality of care, the efficiency of care, and the patient-HCP relationship (performance expectancy); that the dashboard is easy to use (effort expectancy); and that 99DOTS leads to better coordination among HCPs (social influences). However, HCPs described suboptimal facilitating conditions, including inadequate training of HCPs in 99DOTS, unequal changes in workload, and shortages of 99DOTS medication envelopes. CONCLUSIONS: In India's government TB program, 99DOTS had high acceptance by HCPs but variable acceptance by patients. Although some factors contributing to suboptimal patient acceptance are modifiable, other factors such as TB- and HIV-related stigma and poor cell phone accessibility, cellular signal, and literacy are more difficult to address. Screening for these barriers may facilitate targeting of 99DOTS to patients more likely to use this technology.

Evaluation of the Accuracy of 99DOTS, a Novel Cellphone-based Strategy for Monitoring Adherence to Tuberculosis Medications: Comparison of DigitalAdherence Data With Urine Isoniazid Testing.

99DOTS is a cellphone-based strategy for monitoring tuberculosis medication adherence. In a sample of 597 Indian patients with tuberculosis, we compared 99DOTS' adherence assessments against results of urine isoniazid tests collected during unannounced home visits. 99DOTS had suboptimal accuracy for measuring adherence, partly due to poor patient engagement with 99DOTS.