Using a pill box to organise daily doses of antiretrovirals significantly improves adherence and is associated with a greater reduction in viral load and a higher probability of having an undetectable viral load, researchers from the University of California San Francisco report in the October 1st edition of Clinical Infectious Diseases.
In an accompanying editorial Canadian adherence experts say that pillboxes should be widely used, but warn that in patients with very poor adherence, they may not provide enough reinforcement of adherence to show any benefit.
Pillbox organisers, which may contain separate compartments for each dose or each day of the week, are widely available in North America and Europe, and are distributed free of charge by some pharmaceutical companies.
Pillboxes may help patients to spot when they have missed doses, and are also easily portable, releasing people from the need to carry multiple bottles of medicines when they are away from home.
The San Francisco study looked at the effect of pillbox use on adherence in a cohort of 245 HIV-positive patients largely recruited between 1996 and 2000 from homeless shelters and services targeting the downtown `street` population of the city.
The study was a non-randomised analysis of adherence levels, during which participants underwent unannounced pill counts every three to six weeks at their residence over a twelve-month period. Unannounced pill counts reduced the risk that participants with poor adherence would get rid of pills in order to disguise poor adherence, the authors note.
Adherence in patients not using a pillbox was assessed using an electronic medication monitor on the pill bottle of the most frequently dosed drug in their antiretroviral combination.
The analysis controlled for a wide range of confounding factors, including substance abuse, homelessness, prior adherence, viral load, CD4 count, sex, age, ethnicity and sexual orientation.
During the follow-up period 163 participants used a pillbox for at least one month, and pillboxes were used for 43% of the total person-months of observation accumulated during the study.
Sixty-three per cent were taking protease inhibitor-based combinations, often with high pill numbers, and 42% had a previous history of single or dual nucleoside analogue exposure prior to starting triple combination therapy, indicating a high vulnerability to viral rebound and the development of drug resistance.
The mean adherence rate was 73% during the study. Pillbox use was associated with an improvement in adherence of 4.1% - 4.5% compared to non-users.
Pillbox use was more likely in people with a prior history of good adherence and in women, and became more frequent as the study went on.
Three different statistical methods were used to calculate the impact of pillbox use on adherence, and arrived at an estimate that pillbox use was associated with a 0.34 – 0.37log10 greater reduction in viral load. Pillbox use increased the probability of a viral load below 400 copies/ml by 14.2 - 15.7%.
Multivariable linear regression of the adherence percentage (the difference between current and previous pill counts, divided by the prescribed number of doses for the same period) showed that use of a pillbox organiser had a much greater effect on adherence than once-daily therapy (coefficient of 4.47, compared to 0.78 for once-daily therapy).
In an accompanying editorial Edward Mills of the British Columbia Centre for Excellence in HIV/AIDS and Curtis Cooper of Ottawa Hospital note that “for the occasionally non-adherent patient (e.g. one who takes 90% of the prescribed medications, with a missed dose every 1-2 weeks) the pillbox intervention may have a fundamentally beneficial impact on preventing the development of antiretroviral drug resistance.”
But they warn that for patients with a low level of adherence, “a 5% improvement in adherence may shift a patient from maintaining drug levels that are too low to generate drug resistance to a sub therapeutic plasma antiretroviral level that is insufficient to fully suppress HIV but is high enough to provide sufficient pressure to produce drug resistance.”
Despite this, they conclude that pillboxes are “a simple and effective intervention and should be widely used.”
Petersen ML et al. Pillbox organizers are associated with improved adherence to HIV antiretroviral therapy and viral suppression: a marginal structural model analysis. Clin Infect Dis 45: 908-915, 2007.
Mills EJ, Cooper C. Simple, effective interventions are key to improving adherence in marginalized populations. Clin Infect Dis 45: 916-917, 2007.