October 31, 2002
Study subjects who responded to the annual treatment program survey between January 1 and November 1, 2001, reported on the occurrence and severity of symptoms of 42 side effects of antiretroviral agents. Symptoms were classified into subgroups according to whether they were considered subjective or objective and whether or not they would prompt clinical action.
Patients reported what their physician recommended in response to their symptoms in each category, and what they did themselves. Intentional nonadherence was defined as either skipping or altering doses of selective regimen components or temporary cessation of therapy not recommended by their physician. Although high pill burden, complex dosing schedules, and caveats as to timing of medications can result in unintentional imperfect adherence to a drug regimen, this study focuses on patients who alter their regimens on purpose as a direct consequence of adverse drug effects.
Researchers concluded that intentional nonadherence to antiretroviral therapy is common among persons experiencing therapy-related side effects. While the type and severity of adverse effects impact intentional nonadherence, it occurs in relation to symptoms regardless of their strict clinical relevance.
A unique feature of this study is that it explores patients' self-perceived symptoms related to antiretroviral therapy and their subsequent responses in terms of adverse effect management. It describes purposeful alterations in antiretroviral therapy as a direct response to specific adverse symptoms, rather than broadly defined adherence rates.
The study's cohort reported an average of 12 therapy-related symptoms, with most experiencing at least one symptom that they thought was severe. Eleven percent of the subjects admitted to either selectively skipping medications or to taking a drug holiday not recommended by their physicians in order to ameliorate symptoms. Data analysis suggested that patients with a poorer response to therapy were more likely to adjust their medications. Lower educational status was also associated with intentional nonadherence, possibly because, according to the researchers, individuals with lower educational status might have greater difficulty understanding the importance of strict regimen adherence. Or, such patients could be less able or less disposed to voice their concerns to the physician.
The authors stress that 11 percent is probably an underestimate. Study subjects were mostly well experienced in antiretroviral treatment, and had comparatively successful treatment responses, based on average CD4 cell counts and viral loads. Since the survey was voluntary, it could represent a generally compliant sub-group of subjects. Patients might have underreported nonadherence to appear more socially desirable. Furthermore, the figures apply only to a one-year period. Over several years of treatment, a greater proportion of patients may engage in intentional nonadherence. Moreover, physician and patient responses were aggregated by group rather than for each individual symptom, thus making it impossible to assess agreement by symptoms between physician and patient responses to specific symptoms.
Based on previous studies of antiretroviral compliance and the current findings, the researchers suggest that the relevance of subjectively identified symptoms and those not generally considered cause for treatment change or cessation of treatment could be greatly underestimated. Furthermore, actual symptoms and their true relationship to antiretroviral therapy could be less relevant than patients' perceptions.
The authors advise physicians to maintain a fine balance between encouraging patients to maintain efficacious therapy and being alert to the implications of symptoms related to medication use for social and emotional well-being and adherence.
Journal of Acquired Immune Deficiency Syndromes
10.01.02; Vol. 31: P. 211-217; Katherine V. Heath; Joel Singer; Michael V. O'Shaughnessy; Julio S.G. Montaner; Robert S. Hogg