Taking Multiple Non-HIV Drugs Linked to Antiretroviral Treatment Breaks

February 21, 2016

Adult HIV patients taking five or more nonantiretrovirals daily proved more likely to interrupt antiretroviral therapy (ART) in a large Canadian cohort. In this 2011–2013 analysis, patients with a higher daily antiretroviral pill burden also interrupted ART more.

As people live longer with HIV infection, their risk of age-related comorbidity and consequent treatment increases. Polypharmacy, defined in this study as ≥5 nonantiretrovirals daily, raises overall pill burden and the risk of drug-drug interactions that may compromise ART adherence and efficacy. To determine whether polypharmacy affects rates of discontinuing or switching ART in a contemporary cohort, researchers working with the Southern Alberta Clinic Cohort conducted this study.

The analysis focused on Southern Alberta Clinic Cohort members older than 16 years who made at least one study visit between January 2011 and December 2013. All HIV-positive people in southern Alberta received care as part of the cohort. The researchers defined continuous ART as the same three- or four-drug regimen taken for ≥6 months. Regimen simplification did not count as a change in ART. For 15 years the Southern Alberta Clinic Cohort pharmacy has recorded the reasons for every ART change. The research team used pharmacy refill records to determine antiretroviral adherence.

Of the 1190 patients taking ART during the study period, 907 (76%) were men, 569 (48%) were men who have sex with men, and 741 (62%) were between 31 and 50 years old; 746 participants (63%) were white, 245 (21%) black, and 95 (8%) Native Canadian. Two-thirds (68%) of study participants remained on the same regimen throughout the study period and one-third (32%) interrupted ART at some point. Patients who interrupted ART were more likely to be women, ≤30 years old, have a CD4+ count ≤200 cells/mm3 and to have become positive while injecting drugs (all P < .05). Continuous and noncontinuous ART users did not differ by race. While 64% of cohort members were taking once-daily ART, 36% were taking a twice-daily regimen.

Among the 1190 people taking ART, 383 (32%) met the definition of nonantiretroviral polypharmacy (≥5 medications daily). Significantly higher proportions of older people were on polypharmacy: 55% >60 years, 39% 51 to 60 years, 32% 41 to 50 years, 16% 31 to 40 years and 7% ≤30 years (P < .01). Polypharmacy proved significantly more frequent in men, in Native Canadians and in people who became positive while injecting drugs (all P < .05). Polypharmacy was more frequent in patients taking four versus three antiretrovirals (58% versus 31%) and in patients taking twice-daily versus once-daily ART (39% versus 28%).

One-third of the cohort (32%) stopped or switched ART to meet the definition of noncontinuous ART. A higher proportion of people on polypharmacy interrupted ART (37% versus 30%, P < .01). The proportion of people who interrupted ART rose from 25% among those taking one or two antiretroviral pills daily to 42% among those taking more than two antiretroviral pills daily (P < .01).

Among people who discontinued ART, 52% did so because of nonadherence, 31% because of adverse drug effects, 6% because of drug-drug interactions, 6% because of ART failure and 4% for other or multiple reasons. Compared with people older than 50 years, younger cohort members were more likely to discontinue ART because of nonadherence (55% versus 42%, P < .05). Older patients were more likely to discontinue because of adverse drug effects (46% versus 30%, P < .05) and therapeutic changes (24% versus 16%, P < .05).

The authors note that "the interplay between ARV [antiretroviral] and non-ARV drugs has become increasingly complex and challenging for both patient and physician. Effective managing of total pill burden, dosing regimes, drug-drug interactions, as well as toxicities will be increasingly important to ensure that the immense value of ART is not to be diluted or lost in the world of polypharmacy."

Mark Mascolini writes about HIV infection.

Copyright © 2016 Remedy Health Media, LLC. All rights reserved.

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