Adherence interventions and outcomes of tuberculosis treatment: A systematic review and meta-analysis of trials and observational studies

Abstract

BackgroundIncomplete adherence to tuberculosis (TB) treatment increases the risk of delayed culture conversion with continued transmission in the community, as well as treatment failure, relapse, and development or amplification of drug resistance. We conducted a systematic review and meta-analysis of adherence interventions, including directly observed therapy (DOT), to determine which approaches lead to improved TB treatment outcomes.Methods and findingsWe systematically reviewed Medline as well as the references of published review articles for relevant studies of adherence to multidrug treatment of both drug-susceptible and drug-resistant TB through February 3, 2018. We included randomized controlled trials (RCTs) as well as prospective and retrospective cohort studies (CSs) with an internal or external control group that evaluated any adherence intervention and conducted a meta-analysis of their impact on TB treatment outcomes. Our search identified 7,729 articles, of which 129 met the inclusion criteria for quantitative analysis. Seven adherence categories were identified, including DOT offered by different providers and at various locations, reminders and tracers, incentives and enablers, patient education, digital technologies (short message services [SMSs] via mobile phones and video-observed therapy [VOT]), staff education, and combinations of these interventions. When compared with DOT alone, self-administered therapy (SAT) was associated with lower rates of treatment success (CS: risk ratio [RR] 0.81, 95% CI 0.73–0.89; RCT: RR 0.94, 95% CI 0.89–0.98), adherence (CS: RR 0.83, 95% CI 0.75–0.93), and sputum smear conversion (RCT: RR 0.92, 95% CI 0.87–0.98) as well as higher rates of development of drug resistance (CS: RR 4.19, 95% CI 2.34–7.49). When compared to DOT provided by healthcare providers, DOT provided by family members was associated with a lower rate of adherence (CS: RR 0.86, 95% CI 0.79–0.94). DOT delivery in the community versus at the clinic was associated with a higher rate of treatment success (CS: RR 1.08, 95% CI 1.01–1.15) and sputum conversion at the end of two months (CS: RR 1.05, 95% CI 1.02–1.08) as well as lower rates of treatment failure (CS: RR 0.56, 95% CI 0.33–0.95) and loss to follow-up (CS: RR 0.63, 95% CI 0.40–0.98). Medication monitors improved adherence and treatment success and VOT was comparable with DOT. SMS reminders led to a higher treatment completion rate in one RCT and were associated with higher rates of cure and sputum conversion when used in combination with medication monitors. TB treatment outcomes improved when patient education, healthcare provider education, incentives and enablers, psychological interventions, reminders and tracers, or mobile digital technologies were employed. Our findings are limited by the heterogeneity of the included studies and lack of standardized research methodology on adherence interventions.ConclusionTB treatment outcomes are improved with the use of adherence interventions, such as patient education and counseling, incentives...

Video directly observed therapy for supporting and monitoring adherence to tuberculosis treatment in Uganda: a pilot cohort study

“…The End TB Strategy envisions a world free of tuberculosis (TB): zero deaths, disease and suffering due to TB by 2035 [1]. Nonadherence to treatment remains a major obstacle to TB control because it reduces cure rates, prolongs infectiousness and contributes to the emergence of acquired multidrug-resistant strains [2][3][4][5]. Nonadherence to treatment is a challenge particularly in sub-Saharan Africa, where TB rates can be as high as 800 per 100 000, yet resources for healthcare delivery are limited [1].…”

“Kill-TB” Drug Reminder Mobile Application for Tuberculosis Patients at Bengaluru, India: Effectiveness and Challenges

“…The non-adherence rate per 100 persons-months is reduced by 50% and the loss-to follow-up rate is reduced when compared to those without mobile application. Several studies have shown that electronic reminders improve adherence to chronic medication [8]. Patient-centric mobile application and providing human touch to patients through directly observed treatment will strengthen the bonding between the patients and the health system and might improve treatment outcomes.…”

“…Apart from the directly observed treatment (DOT), many e-health strategies have been adopted by different national TB programmes to monitor the treatment adherence with different degrees of success [3]. These strategies include short messaging services, giving missed calls, ingestible sensors, digital pill boxes, smart or mobile phone-based technologies and video observed therapy [4] [5] [6] [7] [8].…”

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“…In a meta-analysis of the trials of fluoroquinolones-containing 4-month regimens for drugsusceptible TB, modest nonadherence was associated with significantly increased risk of unfavorable outcome, in both experimental and control regimens [17]. This underscores the importance of the quality of execution in noninferiority trials, as differential adherence across treatment arms could lead to erroneous conclusions about treatment efficacy [39,45].…”