ART Pill Burden and Dosing Frequency: Do They Matter?

Carlos del Rio, MD reviewing Nachega JB et al. Clin Infect Dis 2014 May 1.


As antiretroviral regimens become more potent and better tolerated, virologic outcomes have improved; regimen simplification has also helped by decreasing pill burden and increasing adherence.


The success of antiretroviral therapy (ART) is directly correlated with adherence, which in turn depends on the convenience and tolerability of the regimens involved. In recent years, ART regimens have become simpler, with lower pill burdens and once-daily dosing.

To evaluate the effects of these changes on ART adherence and virologic suppression, investigators conducted a meta-analysis of relevant randomized, controlled trials published in the literature or presented at conferences in abstract form. Nineteen studies (totaling 6321 adult patients) published between 2004 and 2011 met the inclusion criteria: 11 (totaling 3092 patients) that had been published in a previous meta-analysis (NEJM JW AIDS Clin Care Feb 9 2009) plus 8 additional ones (3283 patients). Of these 19 studies, 7 involved treatment-naive patients, 9 evaluated treatment-experienced patients with virologic suppression, and 3 evaluated treatment-experienced patients with virologic failure; the median duration of follow-up was 48 weeks. Seventeen of the studies reported both adherence and virologic suppression.

Higher pill burden was significantly associated with lower adherence for twice-daily regimens and with worse virologic outcomes for both once- and twice-daily regimens. Adherence rates were modestly higher with once-daily than with twice-daily regimens, but virologic-suppression rates showed no significant difference. Adherence and virologic-suppression rates both decreased over time; however, the decrease in adherence was less with once-daily regimens.


Comment: In this meta-analysis of clinical trials (none of which directly evaluated the effects of fixed-dose, single-tablet regimens), a lower pill burden was associated with both better adherence and better virologic outcomes. However, because the data analyzed were derived from clinical trials — where efforts to provide drugs and maximize follow-up are optimized — they may not be generalizable to clinical settings. Nonetheless, the findings have important implications: As antiretrovirals become generic, payers might elect to have patients “desimplify” their regimens — a change that, by increasing pill burden, could compromise adherence and outcomes.


  1. Nachega JB et al. Lower pill burden and once-daily antiretroviral treatment regimens for HIV infection: A meta-analysis of randomized controlled trials. Clin Infect Dis 2014 May 158:1297. (

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