Socio-demographic of study subjects in Table 2 showed that sex, working status, income, and BMI between cured and LTFU patients were significant difference (p-value of 0.013, 0.010, 0.007, and 0.006, respectively). While age, education level, marital status, and family history of TB between cured and LTFU patients were not significant differences with p = 0.367, 0.635, 0.140, and 0.148, respectively. LTFU was found higher in males than females (64.3% vs. 49%, p = 0.013). A previous study reported that older age and male sex were risk factors for LTFU, whereas patients with higher initial body weight were less likely to be LTFU [12]. A significant association of LTFU with occupation, marital status, and socio-economic status [3].
Loss to follow-up patients in our study were found higher in males, compared to females (64.3% vs. 49%, p = 0.013). Working status between cured and LTFU was also found significantly different (p = 0.010). A high rate of LTFU was found in patients who were unemployed and non-regular employee (66.3% and 51.4%). Male sex and working status affected LTFU probably because male patients should work to provide the needs of their families, while patients of regular employee have a lower rate of LTFU (44.4%) perhaps because they already have permanent jobs and no need to be worried when dividing their times between working and taking DR-TB treatment. Another study also reported that most of non-adherents were males patients, most of them were day-laborers and main earning member [13]. Going to healthcare facility for DR-TB treatment for an employed patient means an absent time from work, and it may pose huge problems, especially for non-regular employees. Working and treatment may also put them in a stress condition, that as soon as they begin to feel better, they will choose to return to work to continue to earn for their families. While female patients, especially who were housewife may have more available time to take their drugs on proper time [3].
Patients with education levels of elementary school, junior high school, and senior high school have higher rates of LTFU, compared to patients with education levels of diploma and above, but the statistical analysis showed no significant difference (p = 0.635). Patients with education level of diploma and above have a lower rate of LTFU (44.4%), although it was not significant statistically. A study in China in Ethiopia found that anti-TB treatment non-adherence was associated with poor TB knowledge [14, 15]. In this study, the lower rate of LTFU in patients with higher education level may due to a higher awareness and better knowledge of their disease, thus increase their compliance for treatment. A higher education level affected the way of thinking, including the ability to overcome problems [16], associated with better adherence to treatment since it increases awareness of the disease [17, 18].
Our study found that income between cured and LTFU patients are significantly different (p = 0.007). Most of subjects in this study have income below 1 million rupiah (rate of 65.3%), showed poor condition. Cost of transport and other needs during treatment are also problems for patients who are in poor condition, and LTFU became their final option [3]. The correlation between poverty and LTFU could be reduced by a strategy in programs, the supply of financial incentives may improve the adherence to treatment [17].
Using structured questionnaires, logistic regression analysis found that negative attitude towards treatment, limitation of social support, dissatisfaction with health service, and limitation of economic status are correlated with LTFU, with p-value of < 0.001, < 0.001, < 0.001, and 0.034, respectively (Table 3). Our findings showed that a strategy to improve treatment adherence needs to combine the aspect of psychological, social, health service, and economic support.
Patients who have negative attitude towards treatment were likely to have 1.201 times more risk for loss to LTFU (Table 3). The aspect of negative attitude towards treatment comprised lack of awareness, myths and misbeliefs regarding the disease, adverse drug and treatment effects, duration and schedule of medication conflicting with daily activities. Education and counseling for DR-TB patients are very important to break the myths and misbeliefs among patients regarding disease, also to inform the patients about the benefits of medication over the adverse effects. A previous study also reported drug side effects and conflicts with the timing of treatment services as the barriers to treatment adherence [19]. Another study found that poor adherence to DR-TB treatment is associated with negative side effects from the treatment, busy work schedules, and financial difficulties [8]. Both patient and regimen were related factors associated with loss to follow-up [20]. Patients who have been previously treated need extra care to ensure treatment completion [21].
Treatment adherence is influenced by many factors, including socio-economic factors and drug toxicity, perceived health benefits, and subjective experience of illness [3]. Independent factors associated with LTFU included patients’ higher self-rating of the severity of adverse drug reaction, while protective factors included receiving any type of assistance from the TB program, better TB knowledge, and higher levels of trust in and support from physicians and nurses [22]. Treatment outcomes were mainly affected by patient individual factors [23].
Limitation of social support correlated with LTFU in this study, comprised stigma and discrimination, and lack of family and social support increased risk for LTFU for 1.163 times (Table 3). Non-adherence to treatment correlated with lack of provider support and social stigma. Resolving medical problems like adverse drug effects, motivational counseling, flexible timings for health-care services, social, family support for patients & improving awareness about disease were required to be enhanced [19]. In certain patients, motivation to continue treatment decreases over time, and when they feel their conditions have improved, they may LTFU from treatment [3]. Patients will need support to overcome the hardships associated with TB and its treatment, including daily adherence, adverse drug reactions, indirect costs, and stigma [4]. Counseling based on behavioral activation theory, information/education materials, and group interactions with other patients showed acceptable to patients to resolve their depression during treatment, suggested the need for counselors in TB clinics [24].
Dissatisfaction with health service (from the physicians and nurses) and limitation of economic status also increased risk for 2.193 and 1.135 times for patients to be loss to follow-up (LTFU) (Table 3). A poor communication between patients and healthcare workers was associated with LTFU [25]. A good communication between health care providers, patients, and their families, and strong social support networks could reduce the stigma [17]. Economic status, including conflicting timing of job and treatment, financial constraints, and late of enablers payment from government also play role in LTFU in our study. Although medicines are provided free, but family liabilities and burden of losing income from work were possible to cause LTFU [3].
Enablers for transportation may minimize the financial barrier to adherence. However, the delay of payment is a problem. The amount of assistance from enablers is limited and transportation cost may exceeds the financial ability of patients, and loss of income when undergoing treatment at health-care facility which is not open for full-day [10]. The WHO also reported that DR-TB patients and their households faced higher catastrophic costs than DS-TB patients, including the combined cost of transportation, food, nutritional supplements, and other non-medical expenditures [1]. Improving treatment adherence is needed, including providing material support (e.g. food, financial incentives, and reimbursement of transport fees) and psychological support [4]. Factors influencing patient adherence to TB treatment are factors of patient-centered, social, economic, health system, therapy, lifestyle, and geographic access [26]. Psycho-emotional and socio-economic interventions provided to TB patients showed beneficial effects on TB treatment outcomes [27].
Certain LTFU patients may be lost their jobs due to undergoing treatment at a health-care facility. Economic factors such as employment status and the need to borrow money when seeking treatment may also influence LTFU [10]. Helping patients to achieve full adherence to TB medication is a complex problem as it is influenced by interplay between many factors. Healthcare managers, providers, and researchers need to consider and address multiple underlying factors when designing adherence interventions [26].
Loss to follow-up from DR-TB treatment is a barrier to cure and control the disease [28]. LTFU patients are a threat to the spread of DR-TB disease in the community. Identified risk factors correlated with LTFU can be used to make a strategy to resolve this urgent problem [29], it is also essential to prevent the community from primary DR-TB infection and to reduce further drug resistance developments [30]. Non-compliance to treatment is complex [3], the role and efforts from all parties are essential. The involvement and support from the combination of health ministry, labor and employment ministry, and social ministry may help to resolve the complex problems of LTFU in DR-TB patients