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 and enablers, psychological interventions, reminders and tracers, and digital health technologies. Trained healthcare providers as well as community delivery provides patient-centered DOT options that both enhance adherence and improve treatment outcomes as compared to unsupervised, SAT alone.

Highlights

  • Adherence to treatment is challenging, given the complexity, modest tolerability, and long duration of treatment regimens currently available for both drug-susceptible and -resistant tuberculosis (TB)

  • When compared to directly observed therapy (DOT) provided by healthcare providers, DOT provided by family members was associated with a lower rate of adherence (CS: risk ratio (RR) 0.86, 95% CI 0.79–0.94)

  • TB treatment outcomes are improved with the use of adherence interventions, such as patient education and counseling, incentives and enablers, psychological interventions, reminders and tracers, and digital health technologies

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Summary

Introduction

Adherence to treatment is challenging, given the complexity, modest tolerability, and long duration of treatment regimens currently available for both drug-susceptible and -resistant tuberculosis (TB). Public health programs have used a variety of strategies to improve adherence at the health system level via financial incentives or enablers to offset the cost of accessing treatment, improving coordination and logistics around TB treatment delivery, and training healthcare providers. Other interventions aimed at supporting adherence through DOT include incentives, which are material or financial rewards provided to those adhering treatment [15], and enablers, which are interventions that allow patients to overcome economic constraints associated with DOT, such as absence from work or the direct and indirect patient costs of accessing TB treatment. Reminder systems and patient tracers are targeted at assisting patients to keep appointments and to take action when patients miss appointments [17] These interventions include reminder letters, phone calls, home visits, and, more recently, short message service (SMS) technology as well as electronic pill boxes. Given the significant losses patients and the health system incur as a result of poor TB treatment outcomes, identifying those interventions that are most likely to improve adherence and outcomes, especially in resource-limited settings, is crucial

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