The relationship between symptom burden and medication adherence documented in this study confirms previous findings (Cooper et al., 2009
; Holzemer et al., 1999
; Ickovics et al., 2002
; Sherr et al., 2008
). In general, patients with lower levels of adherence reported more and worse symptoms compared to those with higher adherence. High adherers reported fewer psychological symptoms, and low adherers reported more physical symptoms.
Hispanic adults in this study were more likely than non-Hispanic adults to report low adherence. Previous studies have yielded inconsistent findings related to racial/ethnic differences in adherence, and the varied results have been attributed to the diversity of customs, health beliefs, and attitudes about treatment across different study groups (Ammassari et al., 2002
). Furthermore, those who did not complete high school were more likely than those with more education to report low adherence. This finding contradicts past studies that have generally found education level to be unrelated to adherence (Ammassari et al., 2002
). Clinicians and researchers should consider how cultural and educational factors might be influencing adherence.
While the sample of transgender adults in this study was small, the low rate of adherence in this subgroup is concerning. Nearly a quarter of the transgender adults reported missing medication during the 3-day assessment. Their reasons for non-adherence also differed compared to men and women, with significantly more transgender adults reporting missed medication because they felt sick or had too many pills to take. Additional research is needed to explore the unique adherence issues faced by this at-risk population.
Of the 32 individual psychological and physical symptoms studied, most were significantly related to level of adherence, although effect sizes were small. Consistent with other studies (Campos, Guimarães, & Remien, 2010
; Kumar & Encinosa, 2009
; Protopopescu et al., 2009
), symptoms of depression and anxiety were associated with non-adherence in the current sample. Trouble sleeping was one of the symptoms most strongly associated with non-adherence. Sleep disturbance was reported by nearly 75% of low adherers, whereas only 45% of high adherers reported this common symptom. Given that sleep disturbance and depression often co-occur and that Phillips and colleagues (2005)
also found that sleep disturbance and depression were associated with poor adherence, future research should further explore the relationship of these symptoms to non-adherence.
Sleep disturbance and fatigue were documented in our previous study as prevalent symptoms among adults with HIV (Lee et al., 2009
) and sleep problems often result in daytime sleepiness, fatigue, and difficulty concentrating. Since “forgetting” was the most common reason given for non-adherence and more than one third of the current sample reported “sleeping through dose time,” further examination of the relationship between sleep and adherence is warranted. Effective management of these common symptoms could result in better adherence as well as improved clinical outcomes and quality of life.
The results of this cross-sectional examination of baseline measures did not indicate whether a causal relationship existed between symptom experience and adherence, and if so, whether symptom experience was primarily the cause or result of non-adherence. In all likelihood, the nature of the relationship depends on the symptom. Symptoms such as difficulty concentrating or swallowing likely interfere with adherence, while pain and cardiopulmonary symptoms may be the result of poor adherence. As specified in the UCSF Symptom Management Model, most symptoms are likely both the cause and result of poor adherence, reflecting a dynamic interaction between symptom experience, management, and outcome. For example, feeling depressed or fatigued may make it difficult to take medications, but missing medication may also exacerbate these symptoms. Future longitudinal work is needed to help determine the direction of effects between treatment adherence and symptoms common among adults with HIV.
At least a portion of the association between poor adherence and symptom experience may not be causal at all, but rather due to other factors such as lifestyle. Substance abuse, mental illness, homelessness, and social isolation have been identified as predictors of poor adherence (Leaver, Bargh, Dunn, & Hwang, 2007
; Mellins et al., 2009
) and likely lead to diminished quality of life. While those testing positive for illicit drugs and those reporting a severe mental health diagnosis were excluded from this sample, many of the participants were nonetheless struggling with drug addiction and mental health issues. The independent negative effects these factors have on both adherence and symptom experience may partially account for their association. If such is the case, it will be essential to address these underlying issues in order to improve medication adherence.
Avoiding side effects was one of the less common reasons given for non-adherence; nonetheless, it was reported by 24% of the sample. Symptoms such as nausea, vomiting, dry mouth, constipation, and a change in the way food tastes may be medication side effects, and adherence could potentially exacerbate these symptoms. While it was beyond the scope of this study to examine whether participants perceived their symptoms as disease-related or treatment-related, such attributions are clearly relevant to adherence behaviors (Johnson, Stallworth, & Neilands, 2003
) and would strengthen future research in this area.
Like all self-report adherence measures, those used in this study (the modified ACTG scale and the daily log of missed medications) likely overestimated the level of adherence. In fact, the proportion (14%) falling in the non-adherent category (scores 21–36) was substantially smaller than the 75% reported in Holzemer’s study (2006)
. While this difference may be due, at least in part, to the exclusion of those testing positive for illicit drugs or reporting a severe mental health diagnosis from the current sample, actual adherence levels are likely lower than reported in this study. Despite this limitation, the overestimated adherence level during the prior month was able to distinguish levels of disease burden, as well as symptom prevalence and experience in the previous week. Furthermore, the number and frequency of reasons reported for non-adherence during the previous month was strongly associated with prospective reports of missing medication during a 3-day monitoring period, thereby providing convergent validation for the retrospective measure.
Another limitation of this study was the lack of information as to which medications were missed or how much. Patients are likely to be selective about medications they miss, and clinical effects of non-adherence may vary by medication as well as by quantity of medication involved. Future research in this area should include these important adherence parameters. While this study did not find that the adherence groups differed with respect to the number of medications they took, future research should also evaluate pill burden or the number of pills included in the patient’s medication regimen. Finally, this study was not specific to adults on ART, and it was interesting to note that those currently taking ART were no more or less adherent than those not taking ART. Adherence to non-ART medications should be considered in future studies, particularly given the probable consequences for effective symptom management.
In light of the importance of medication adherence to achieving optimal clinical outcomes, numerous interventions have been developed to support patients in adhering to their medical regimens (Holzemer et al., 2006
; Safren et al., 2009
). Most focus on one or more correlates of adherence, such as medication beliefs or social support, but few have been effective (Simoni, Pearson, Pantalone, Marks, & Crepaz, 2006
). Given the strength of the relationship between symptom experience and adherence, interventions that effectively manage symptoms may also help to enhance adherence, clinical outcomes, and quality of life in those living with HIV.