Potential factors affecting adherence with HIV therapy

Abstract

Introduction A greatly increased level and duration of suppression of HIV replication has become possible with the use of protease inhibitors in combination with nucleoside analogues as antiretroviral therapy [1,2]. The long-term effectiveness of protease inhibitors, and other antiretroviral medications, is dependent upon strict adherence to the prescribed regimen, since HIV resistance to these drugs can develop with subtherapeutic doses [3,4]. Consequences of poor adherence include not only diminished outcome for the patient, but also the public health threat of multidrug-resistant HIV, and widespread transmission of drug-resistant virus, similar to that seen with multidrug-resistant tuberculosis [5]. The aim of this article is to review the scientific literature on drug adherence in studies based on methodologic criteria and among patient populations relevant to HIV infection. We reviewed the adherence literature on patients with HIV infection and on two other groups that may have relevance to the adherence issues faced by HIV-infected individuals: patients with chronic illness and patients with mental illness. Chronic illness was chosen because it is well-established that HIV infection has a median incubation period of 10 years or more [6], with multiple comorbid complications, and complex treatment regimens. Mental illness was chosen because psychiatric diagnoses are common in patients who acquire HIV [7–9]. We divided factors associated with decreased adherence into four broad categories: demographic characteristics, psychosocial/ behavioral characteristics, clinical aspects, and health-care administration and delivery. Much of the literature use the words ‘compliance’ and ‘adherence’ interchangeably, although adherence has come to be considered the less pejorative term. Although they are inherently related, several articles reviewed described individual definitions of the terms. Adherence relates to the extent to which the patient follows a prescribed regimen [10–12]. For example, a patient may take his/her medication 80% of the time. Conversely, Young et al. [10] reported adherence in terms of a default rate from follow-up, or significant deviation from a prescribed regimen. The specific characteristics of what the adherence or default rate is measuring depends on the prescribed regimen; for example, it may apply to medication-taking behaviors, dietary intake or physical therapy. Compliance, on the other hand, is an overall evaluation of adherence. Those patients who adhere to their prescribed medical regimen 80% of the time may be considered to show high compliance, whereas those patients who demonstrate 50% adherence may be demonstrating moderate or low compliance. The level of compliance may vary between patients depending on the type of medicine prescribed, the type of illness, and the accompanying level of symptoms. Evaluation of compliance should also consider the threshold of therapy necessary for effectiveness. For example, with triple combination antiretroviral therapy, it is necessary to take a high proportion (90–100%) of doses to maintain suppression of viral replication [13,14]. In contrast, prophylactic therapy for Pneumocystis carinii pneumonia may be forgiving of an adherence of less than 90–100% [15–17]. Demographic characteristics Although it has been well demonstrated that certain demographic and HIV risk groups have poorer access to therapy [e.g., African-Americans [18,19] and injecting drug users (IDU) [20]] few data are available on the influence of these factors on adherence among HIV-infected patients. Demographic characteristics have been associated with decreased adherence in a variety of disorders, including chronic illness, mental illness, and amongst the elderly. Age Adherence increases with age, except in the most elderly (those aged over 75 years) [21]. Often, the very elderly have more complex medical regimens and more comorbidities, such as vision, hearing, or memory impairment. In comparison, studies of medication adherence in patients aged under 75 years with chronic or mental illness showed a positive correlation between age and adherence [10,11,22,23]. In one prospective evaluation of patients with HIV that addressed this issue, age did not correlate with adherence [24]. However, HIV-infected individuals are typically no older than 50 years [25]. Thus, risks associated with old age may not be a major issue. Gender In several studies of patients with HIV infection, chronic illness, mental illness, and the elderly, male gender was associated with decreased adherence [10,11,26–28]. However, other studies have not found a significant association between men and decreased adherence. Notably, in one study of HIV-infected patients, it was observed that women were missing a higher percentage of clinic visits than men. As a result, free on-site child care was provided, and adherence with scheduled visits improved dramatically [26]. In situations where women are responsible