INTRODUCTION — Tuberculosis (TB) is nearly always curable if patients are treated with effective, uninterrupted antituberculous therapy. Adherence to treatment is critical for cure of individual patients, controlling spread of infection, and minimizing the development of drug resistance [1,2].
Issues related to adherence to treatment of drug-susceptible TB in adults will be reviewed here. The clinical approach to treatment of TB is discussed in detail separately. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection" and "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults with HIV infection: Initiation of therapy" and "Treatment of drug-resistant pulmonary tuberculosis in adults".)
CHALLENGES OF ADHERENCE — Incomplete adherence to treatment has been identified as the most serious problem in TB control [3] and a major obstacle to the elimination of the disease [4]. In one retrospective study including 184 patients with TB in New York City (nearly half of whom were nonadherent), the nonadherent patients took longer to convert sputum to negative culture results (254 versus 64 days), were more likely to acquire drug resistance (relative risk 5.6), and required longer treatment regimens (560 versus 324 days) [5].
Adherence to TB treatment can be particularly challenging; the duration of treatment is long (usually six months or longer), combination therapy is required, and side effects may be unpleasant. Cost of medications (even relatively small copays or deductibles) can be a serious barrier to adherence if not covered by the public health system. Furthermore, patients often experience rapid improvement in symptoms, which may obfuscate the importance of continuing prolonged treatment with drugs that may be perceived as unnecessary.
Factors affecting adherence — Successful treatment among patients with TB may be influenced by several factors:
●Severity of symptoms
●Access to medical care
●Number of medications and their side effects
●Availability and cost of medications (to the patient)
●Dosing frequency
●Duration of treatment
●Personal and social characteristics of patients and providers
●Cultural beliefs of patients and providers and trust in the diagnosis
●Cultural sensitivity of providers and the relationship between provider and patient
●Quality of training among providers
●Quantity and quality of information available about TB
●Extent of patient knowledge about TB and the importance of completing a lengthy treatment regimen even if feeling well
●Commitment of public health system to TB treatment
●Political, legislative, and economic factors
Health care providers must evaluate potential obstacles to treatment and facilitate educating and supporting patients to take medications as prescribed. A poor caregiver-patient relationship is an important cause of nonadherence.
Risk factors for nonadherence — In general, up to half of patients do not follow medical recommendations or use medications as prescribed [6,7]. No single group has been consistently identified to be at risk for nonadherence; the following patients may benefit from close monitoring:
●Patients who have previously failed to complete a regimen of antituberculous therapy (for treatment of active disease or latent infection) or who have had difficulty complying with other medical therapies
●Physically, emotionally, or socioeconomically challenged patients
●Patients unable to pay for medications
●Patients actively abusing drugs, alcohol, or other addictive substances
●Patients who do not believe they have TB or who do not understand the importance of treatment and/or have cultural beliefs opposing treatment
In one series of patients with TB in New York City, an increased rate of nonadherence was observed among African-Americans, people who inject drugs, people experiencing homelessness, people with alcohol use disorder, and people with human immunodeficiency virus (HIV) infection [5]. Multivariate analysis noted that the only consistent predictors of nonadherence were injection drug use and homelessness.
Physicians and other health care workers also have difficulties with adherence [8].
STRATEGIES TO IMPROVE ADHERENCE — Treatment strategies should employ a patient-centered case management approach, using directly observed therapy (DOT) as a tool to maximize adherence [1]. Case management with DOT (at least at the start of treatment) using trained nurses has become a standard of care in TB control and prevention [9]. Other strategies include provision of free medications, use of fixed dose multiple drug combination tablets, patient education, and vouchers for transportation and other needs.
Comprehensive case management — Using this strategy, teams of personnel assume responsibility for case management, continuity of care, and follow-up. Each TB case or suspect is assigned a public health case manager who is responsible for coordinating all aspects of that patient’s care, usually giving the patient a major voice in deciding how care is administered. Description of this strategy are contained in the United States Centers for Disease Control and Prevention (CDC) module on TB: "Managing Tuberculosis Patients and Improving Adherence" [10] the publication by the Rutgers Global TB Institute: Tuberculosis Case Management: A Guide for Nurses (2017) [11].
Patient education — Patient education that is culturally and linguistically appropriate (in combination with other interventions) while minimizing stigmatization is essential for ensuring adherence. The use of simple terms together with both written and pictorial materials are all important. Educational efforts should be directed at identifying the patient's perception of barriers to adherence and at building trust with the health care delivery system.
Use of fixed-dose combination therapy — The use of fixed-dose combinations of antituberculous drugs simplifies therapy and reduces the possibility of missing a component of a multidrug regimen. These preparations reduce the likelihood of acquired drug resistance and are widely used around the world [12]. Combination drugs in the United States have included Rifamate (isoniazid plus rifampin) and Rifater (isoniazid, rifampin, and pyrazinamide); however, their production was discontinued by their manufacturer in June 2020.
Directly or video observed therapy
●Definition and use - Directly observed therapy (DOT) involves observation by a health care provider watching as a patient swallows each dose of antituberculous medication [1,13]. We are in agreement with the 2016 American Thoracic Society, United States Centers for Disease Control (CDC), and Infectious Diseases Society of America guidelines, which suggest using DOT (rather than self-administered therapy) for routine treatment of patients for all forms of TB [1]. In March 2023, the CDC updated this recommendation to include video DOT (vDOT) as an equivalent alternative to in-person DOT [14].
●Prioritizing DOT resources - If routine DOT is not feasible, it should be prioritized for patients with the conditions summarized in the table (table 1). Decisions regarding implementation of observed therapy may be based on local rates of treatment completion and individual patient circumstances. In many programs, patients are observed taking their medications on weekdays and self-administer medications on weekends.
●Efficacy
•DOT - DOT programs require a significant commitment of resources but have been shown to be very effective [13,15-17]. One study of the community-based DOT program in Baltimore, Maryland, illustrated the benefits derived from DOT; during the 1980s and early 1990s, Baltimore experienced a substantial decline in TB incidence while TB incidence elsewhere in the United States increased [16].
Some studies have observed that DOT did not alter rates of cure, treatment interruption, or other outcomes [18,19]. A systematic review of the effectiveness of DOT including 34 studies found that, while overall rates of treatment failure and relapse were low, considerable variability among studies existed in actual compliance and follow-up [20]. A subsequent systematic review including six trials in five mostly high-TB incidence countries concluded that DOT alone did not offer benefit over self-administered care [21]. DOT must be considered a key component of an active case management system in which individual relationships between caregivers and patients form the basis for a treatment plan to ensure safe continuity of treatment.
•Video DOT (vDOT) – The growth of technology has created new opportunities to deliver care via vDOT for patients with TB. vDOT systems must meet jurisdictional privacy requirements. Several studies in high- and low-resource settings have shown that vDOT is effective, feasible and economical [22-26]. In one randomized trial including more than 220 patients with TB in England managed with observed therapy via DOT (observations three to five times per week in the home, community, or clinic settings) or vDOT (daily observation using via mobile phone), completion of ≥80 percent of scheduled observations during the first two months after enrollment was achieved more frequently among patients on vDOT than among patients on DOT (70 versus 31 percent; adjusted odds ratio 5.48, 95% CI 3.10-9.68) [26]. More than half of enrolled patients had a history of homelessness, imprisonment, drug or alcohol use, or mental health problems.
Electronic medication monitoring — Electronic medication monitoring utilizes real-time recording of electronic pill box-opening data to facilitate adherence monitoring by health-care providers.
The efficacy of this tool was evaluated in a trial including 278 patients age ≥15 years with TB disease in Tibet randomly assigned to receive TB treatment administered via an electronic medication monitor (including audio adherence reminders, recorded box-opening data transmitted to health-care providers, and a smartphone app to enable text, audio, and video communication between patients and health-care providers) or usual care plus a deactivated electronic medication monitor (which recorded box-opening data that was not made available to health-care providers) [27]. Poor adherence (defined as missing ≥20 percent of planned medication doses in the month) was observed more frequently in the control group (37 versus 10 percent of treatment months); disease cure was observed more frequently in the intervention group (94 versus 73 percent).
Digital reminders — For settings in which case management with observed therapy is not feasible, use of digital reminders may be beneficial. In a randomized trial in Kenya including more than 1100 patients with TB managed with or without use of interactive text message reminders to take therapy, rates of unsuccessful treatment outcomes were lower among patients who received digital reminders (4.2 versus 13.1 percent) [28].
Incentives and enablers — Incentives and enablers are used to encourage treatment adherence. Incentives are small "rewards" given to patients who adhere to the prescribed treatment regimen and maintain regular clinic visits. Enablers allow the patient to receive treatment more easily (eg, bus tickets or other means of transportation).
Incentives (such as food supplements, food vouchers, cash, and clothing) may be provided to patients to optimize nutrition and cover personal costs for travel and missing work [29]. Material incentives and enablers may have some positive short-time effects on clinic attendance, particularly for marginal populations, but there is insufficient evidence to know if they can improve long-term adherence to TB treatment [30]. Some data suggest that illicit drug users adhere to DOT at equal or higher rates than other patients if appropriate incentives and enablers are offered [31].
Hospitalization — Outpatient treatment with DOT may not be sufficient for adherence in some cases [32,33]. In such circumstances, long-term hospitalization (voluntary or involuntary) may be necessary. In one series of 166 patients in Massachusetts, a dedicated medical-psychosocial inpatient unit facilitated completion of therapy in 97 percent of cases; hospitalization was required for the duration of therapy in 25 percent of cases [34]. Among 67 nonadherent patients in California detained in prison rather than a hospital ward, a lower completion rate was observed (84 percent) [35]. Involuntary confinement is a strategy of last resort [36].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and treatment of tuberculosis".)
SUMMARY AND RECOMMENDATIONS
●Tuberculosis (TB) is nearly always curable if patients are treated with effective, uninterrupted antituberculous therapy. Adherence to treatment is critical for cure of individual patients, controlling spread of infection, and minimizing the development of drug resistance. (See 'Introduction' above.)
●Incomplete adherence to treatment has been identified as the most serious problem in TB control and a major obstacle to elimination. Treatment adherence can be particularly challenging in the setting of TB; the duration of treatment is long (usually six months or longer), combination therapy is required, and side effects may be unpleasant. (See 'Challenges of adherence' above.)
●Patients at risk for nonadherence include those who have previously failed to complete a regimen of antituberculous therapy, those with physical or mental disability, those unable to pay for medications, those who are actively abusing addictive substances, and those who do not understand the importance of treatment and/or have cultural beliefs opposing treatment. (See 'Risk factors for nonadherence' above.)
●Strategies to improve adherence include patient-centered care through comprehensive case management, directly observed therapy (DOT), provision of free medications, use of fixed-dose multidrug combination therapy if feasible, patient education and involvement in management decisions, and vouchers for transportation and other needs. (See 'Strategies to improve adherence' above.)
●Directly observed therapy requires observation by a health care provider as a patient swallows each dose of antituberculous medication; this may be done in person or by video. We recommend using DOT (rather than self-administered therapy) for patients with the conditions summarized in the table (table 1) (Grade 1B). In addition, we suggest using DOT (rather than self-administered therapy) for routine treatment of patients for all forms of TB (Grade 2C). Video observed therapy is a reasonable alternative to DOT in settings where feasible. (See 'Directly or video observed therapy' above.)
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