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October 2016
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Is Memory Really the Problem in ART Adherence?
Christopher J. Hoffmann, MD, MPH, Johns Hopkins University

An undetectable HIV viral load is the sine qua non of effective antiretroviral therapy (ART). Once the correct ART regimen is prescribed, achievement of an undetectable viral load then depends on sustained adherence. The authors of a recent study in AIDS Care (Kalichman SC, et al.; PMID 27535297) sought to better understand and differentiate between factors associated with moderate and severe non-adherence. Moderate non-adherence was defined as 75% to 95% of medication doses taken as prescribed; severe non-adherence was defined as <75% of doses taken as prescribed.

The authors used computerized interviews to collect patient self-reported data on symptoms, side effects, use of common reminder strategies, depression, life stress, and alcohol consumption. The authors also used urine testing to assess for recent illicit drug use. Over a 1-month period, participants were contacted three times for telephone-based pill counts. Participants who had missed doses were then asked about cognitive, organizational, mental health, substance use, and structural barriers to adherence. 

The team followed 214 severely non-adherent and 342 moderately non-adherent participants for 1 month. A large and equal proportion of patients in each group used memory aids to support adherence, including pill boxes, alarms, routine timing of pills, journals, reminders from family members, or posted reminder signs. Although a larger proportion of the severely non-adherent participants reported having forgotten or having been too busy to take medications, the number was not statistically significant. Of the severely non-adherent, 54% reported forgetting compared with 41% of the moderately non-adherent. A larger and statistically significant difference in adherence was related to side effects, running out of pills, and consumption of alcohol (see table below). Depression and stress were also higher among severely non-adherent participants.

Factors Affecting ART Adherence
Participants Reporting this Effect,
by Level of Non-Adherence
Medication side-effects
Running out of pills
Consumption of alcohol
The results of this study suggest that even when adherence reminder strategies are used, they are not effective in helping patients overcome factors related to both severe and moderate non-adherence, including, in this group, alcohol use, access to medications, and mental health challenges. 

This study did have some limitations. The researchers followed participants for just 1 month, and the results were not strong: 68% of the severely non-adherent had undetectable viral loads, and less than 50% of non-adherence among participants was associated with the factors named above.

Nonetheless, the results highlight the roles that mental health, substance use, and structural barriers may play in reducing adherence to ART. The findings also suggest that other, yet-to-be identified factors are at play as well. Perhaps most importantly, the standard focus on memory, reminders, and memory aids may not be helpful in significantly improving adherence among those with demonstrated non-adherence, and we need to dig deeper to help our patients take the medications that will suppress their viral loads.
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HIV Clinical Guidelines Program 
New York State Department of Health AIDS Institute
In collaboration with the Division of Infectious Diseases
Johns Hopkins University School of Medicine

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