Bulletin of the World Health Organization

Anti-tuberculosis medication side-effects constitute major factor for poor adherence to tuberculosis treatment

Niyi Awofeso a

Two significant issues that require further clarification in Garner et al.’s stimulating paper (Promoting adherence to tuberculosis treatment1) are the impact of medication side-effects on treatment adherence as well as how adherence to tuberculosis (TB) chemotherapy should be defined and monitored. The treatment regimen recommended within the DOTS approach is associated with significant side-effects. Side-effects such as hepatitis, dyspepsia, exanthema and arthralgia were responsible for termination of therapy in up to 23% of patients during the intensive phase.2 Medication side-effects were also found to be significantly associated with defaulting.3 At Kyrgyzstan prisons, where the author worked as a TB doctor in early 2007, medication side-effects were among the most common reasons for patient non-attendance at DOTS clinics. The author observed similar non-attendance and defaulting trends among community-based TB patients in northern Nigeria during the 1990s. The side-effects profile of TB chemotherapy is magnified in patients with concurrent HIV treatment and/or prior history of hepatitis,4 and those being treated with second-line drugs for multidrug-resistant TB, during which as many as 86% of patents may develop medication side-effects.5,6 To minimize the adverse impact of medication side-effects in TB treatment adherence, it is important that TB health staff are adequately trained on their recognition and management. Such training should include how to provide concise pretreatment counselling to patients on possible side-effects of treatment.7 It is also important that medications for managing side-effects should be ordered concurrently with the ordering of anti-TB chemotherapy to facilitate timely and adequate treatment of such side-effects.

The DOTS strategy contains elements of adherence and compliance. While these terms were initially used synonymously and are still commonly used interchangeably in TB literature, they have subtle but noteworthy significant differences. The term “adherence” (or “patient-centred compliance”8) refers to the extent to which patients follow a prescribed regimen. It implies a more active and collaborative involvement of patients working with health-care providers in managing their treatment. “Adherence” is currently preferred to “compliance” in medical literature as it portrays a more respectful and active role of the patient in disease management. It captures the increasing complexity of TB chemotherapy by characterizing patients as independent, intelligent and autonomous people who take active and voluntary roles in defining and pursuing goals for their medical treatment. The extent of treatment adherence may be facilitated by positive or negative attributes related to health system, social/family issues, personal factors, and drug factors (e.g. medication side-effects are negative drug attributes while a fixed-dose combination is a positive drug attribute in relation to treatment adherence). Empowerment of people with TB, and communities, through advocacy, communication and social mobilization as well as patient and community participation in TB care are important in facilitating treatment adherence using the DOTS approach.9

In exceptional situations, the DOTS approach of facilitating adherence might not achieve its objectives, since patients need to make themselves available for treatment and are less likely to do so if they are imprisoned, suffer medication side-effects or experience homelessness, drug addiction, unemployment or alcoholism.4,10 In Kyrgyzstan prisons, the practice of self-administered anti-TB treatment on weekends was discontinued in March 2007 due to repeated documented evidence that many patients were trafficking their weekend TB medications, despite concerted efforts aimed at enhancing patient empowerment and peer support.

The most cited definition of treatment compliance is by Haynes – “the extent to which a person’s behaviour (in terms of taking medication following diets, or executing lifestyle changes) coincides with medical or health advice”.11 “Compliance” may be used to describe the “right of public health authorities to demand adherence”1 such as by compelling patients to take TB chemotherapy using Public Health Detention Orders.12 Or it may be used as a framework to evaluate adherence. For example, patients who adhere to TB medication as prescribed 95% of the time are said to demonstrate high compliance, while patients who adhere for 40% of the time are said to demonstrate low compliance.

The World Health Organization defines a TB treatment defaulter as a patient whose treatment was interrupted for two consecutive months or more. It indicates a closure of the current treatment, and documents that patients’ compliance has been 0% for so long. As with HIV treatment, TB therapy requires high (> 90%) compliance to facilitate cure. Good adherence results in high compliance and absence of treatment default. Default rate is a crude approach to adherence monitoring, since it does not really reveal why the patient interrupted treatment for 2 or more consecutive months. Promptly implementing compliance assurance measures provide for better adherence monitoring than defaulter tracing, provided that a baseline compliance level is set at which investigation of the reasons for poor adherence can be undertaken. Currently at the Kyrgyzstan prison TB project, we undertake investigation of reasons for poor adherence if a patient misses at least two doses of anti-TB treatment in a week. This “patient contact” baseline period is in line with the maximum duration of non-adherence that will adversely impact on the efficacy of treatment.13



  • School of Public Health & Community Medicine, University of New South Wales, Sydney, NSW, Australia.