Chronic hepatitis B (CHB) is responsible for increasing mortality and morbidity worldwide with liver cancer related mortality increasing globally, as the population living with hepatitis B infection ages, attributable mortality from other causes of death falls [1] . In 2015, the World Health Organisation (WHO) set ambitious targets for CHB including 80% of eligible people receiving treatment and a 65% reduction in attributable mortality by 2030 [2]. Measuring viral suppression in people living with CHB is one of the 10 core indicators in the monitoring and evaluation framework for viral hepatitis produced by the WHO, and a measure of retention in care and adherence to treatment for people receiving antiviral therapy [2, 3].
Antiviral treatment is effective at both preventing progressive liver damage and liver cancer in people living with CHB who have active viral replication and ongoing liver inflammation, or who have established cirrhosis [4, 5]. Effective treatment results in a low or undetectable viral load, accompanied by normalization of hepatic transaminase levels (such as alanine aminotransferase, ALT). This can be achieved by using recommended first line antiviral agents entecavir or tenofovir, which are well tolerated, have high barriers to development of antiviral resistance, can reduce the risk of cancer by up to 75% over several years and can reverse established cirrhosis [4,5,6]. The optimal duration of antiviral treatment is yet to be defined, but treatment, once initiated, is most often considered to be indefinite or life-long [5]. Commencement of antiviral treatment is only a first step; as is the case for other chronic diseases requiring ongoing treatment and adherence to therapy is required to ensure effectiveness and to prevent viral breakthrough and the potential development of resistance [7].
Treatment adherence is a dynamic process in individuals and periods of poor adherence may result from temporary or more long-term disengagement from care due to competing social pressures, moving place of residence, difficulty attending clinical appointments and/or pharmacies, or interruption of supply of medication due to financial pressures, or day to day pressures that result in irregular dosing [8]. Poor adherence is also more common when the condition being treated is asymptomatic and the treatment regimen results in no overtly identifiable sense of improvement in health status [8,9,10]. Adherence is improved in people who have knowledge of their condition and in older individuals, and when the perceived severity of the condition is higher [8].
With new global goals to increase numbers of people with CHB on treatment, assessing and maximizing adherence will become an increasing challenge in all settings. A recent systematic review including 30 studies with different adherence measures estimated overall adherence to treatment in CHB with oral therapy was 75% and was similar in both high and low income settings [11]. Factors that have been shown to be related to poor adherence have included forgetting and change to routine, younger age, higher physician turnover and recent initiation of therapy [11,12,13,14,15]. Adverse reactions to medication can also result in poor adherence however antivirals for CHB have a low side effect profile and rarely adverse outcomes [16]. In a previous study we reported low adherence in 1026 participants was associated with age less than 35 years, inconsistency in clinical care and hospital site but not with type of oral antiviral prescribed [13].
Adherence can be measured by self-report, physician report, measurement of drug levels (dependent on assay availability), direct measurement with memory cap bottles and indirectly through pharmacy data [17]. Pharmacy adherence measures (PAMS) estimate medication in hand during an observed treatment period, can be easily calculated from pharmacy records and are less likely to have bias inherent in self-assessment or physician estimates, but represent only the maximal possible adherence during a time-period; actual administration of dispensed medications is not monitored [18]. Medication possession ratio (MPR) has been most commonly used as a measure of PAMS.
$$ \mathrm{Medication}\ \mathrm{possession}\ \mathrm{ratio}\ \left(\mathrm{MPR}\right)=\frac{\mathrm{Number}\ \mathrm{of}\ \mathrm{pills}\ \mathrm{dispensed}}{\mathrm{Number}\ \mathrm{of}\ \mathrm{days}\ \mathrm{in}\ \mathrm{time}-\mathrm{period}} $$
In the treatment of HIV with highly active antiretroviral therapy adherence, the MPR has been correlated with viral outcomes and mortality [18]. In the context of CHB, an MPR cut-off to determine poor adherence of 0.90–0.95 has previously been arbitrarily chosen without clear reference to viral outcomes and/or mortality and morbidity [12, 19].
In Australia about 6% of all people living with CHB are receiving treatment with oral antivirals, predominantly entecavir (45%) and tenofovir (28%) [20, 21]. Antiviral medication has primarily been dispensed by public and private hospitals at a cost to the individual of US$6–$39 per 2 months of supply. There has been limited prescribing in the community context. An estimate of adherence or the number of people taking treatment who are virally suppressed or adherent to therapy has not yet been incorporated into the cascade of care at a national or jurisdictional level [20, 22].
The aims of this multicentre study were to evaluate virological outcomes in Australian setting, determine the proportion of patients with adequate viral suppression on treatment and to establish an evidence-based MPR definition of poor adherence based on the incidence of poor viral outcomes in patients receiving long term oral antiviral therapy for CHB.
