18 July 2012
Length of antiretroviral therapy (ART) interruption may have a greater impact on HIV control than percentage of time with sufficient drug concentration, according to results of a 16-study longitudinal North American analysis.
Research shows that good antiretroviral adherence is critical to achieving and maintaining an undetectable viral load. But much remains to be learned about what adherence patterns confer the greatest antiviral benefit and how adherence patterns affect different antiretroviral regimens.
To address those issues, researchers analyzed longitudinal data pooled from 16 antiretroviral trials conducted from 1997 to 2009 across the United States and Canada. All studies used the Medication Event Monitoring System (MEMS), which electronically records every time a patient opens a pill bottle and is regarded by some as the most accurate way to measure medication adherence.
The investigators calculated two adherence outcomes: (1) percentage of time with sufficient drug concentrations (“covered time”) and the length of the longest treatment interruption during the 28 days before a viral load measurement. They used logistic regression analysis to estimate how these adherence measures affected chances of having a viral load above 400 copies/mL.
The study involved 1088 trial participants who had 3795 viral load measurements during the studies. Both lower covered time and longer ART interruptions had a dose-response relationship with odds of a detectable viral load: In other words, the less the covered time, the greater the chance of a load above 400 copies/mL, and the longer the interruption, the greater the chance of a load above 400 copies/mL.
Compared with a covered time of 93% to 100%, covered time of 0% to 25% more than tripled the odds of detectable viremia (odds ratio [OR] 3.22, 95% confidence interval [CI] 2.48 to 4.19). Compared with a treatment interruption of 0 to 48 hours, an interruption of 21 to 28 days conferred nearly a 4-fold higher odds of a viral load above 400 copies/mL (OR 3.65, 95% CI 2.77 to 4.81).
These estimates did not vary from one antiretroviral regimen to another.
“Of the patterns of adherence,” the researchers propose, “longer interruptions may have greater impact than covered time.”
They suggest that future research should “investigate additional methods for examining adherence patterns, understanding the determinants of consecutive missed doses and [evaluate] interventions designed to address interruptions in treatment.”
Source: Becky L. Genberg, Ira B. Wilson, David R. Bangsberg, Julia Arnsten, Kathy Goggin, Robert H. Remien, Jane Simoni, Robert Gross, Nancy Reynolds, Marc Rosen, Honghu Liu, for the MACH14 Investigators. Patterns of antiretroviral therapy adherence and impact on HIV RNA among patients in North America. AIDS. 2012; 26: 1415-1423.
For the study abstract
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