Taking a once-daily treatment regimen over a twice-daily regimen may slightly improve adherence, but not necessarily virologic suppression, according to study results presented at EACS 2013 in Brussels, Belgium. However, regardless of dosing frequency, a lower pill burden was correlated with better adherence and virologic suppression.
The study results, presented by Jean Nachega, M.D., were derived from a meta-analysis of 19 randomized clinical trials from around the world conducted between 2004 and 2011, spanning a total of 6,312 participants. Seven studies included treatment-naive patients, nine studies included treatment-experienced patients with virologic suppression, and three studies included treatment-experienced patients who had experienced virologic failure after switching to a new regimen. The researchers set out to compare rates of adherence and rates of virologic suppression in patients receiving once-daily antiretroviral therapy regimens versus patients receiving twice-daily regimens. Median follow-up time was 48 weeks.
When measuring rates of adherence:
- For treatment-naive patients, there was a 4% advantage for once-daily regimens over twice-daily regimens, a small but statistically significant difference (P = .0007).
- For treatment-experienced patients with virologic suppression, there was about a 1% advantage for once-daily regimens, which was also statistically significant (P = .002).
- For treatment-experienced patients with virologic failure, there was a 6.59% advantage for once-daily regimens, again statistically significant (P = .0002).
When measuring rates of virologic suppression:
- For treatment-naive patients, there was a 1.06% advantage for once-daily dosing over twice-daily dosing, which barely achieved statistical significance (P = .05).
- For treatment-experienced patients who achieved virologic suppression after switching to a new regimen, there was a 1% advantage for once-daily dosing, which fell well short of statistical significance (P = .99).
- For treatment-experienced patients who experienced virologic failure after switching to a new regimen, there was a 1.03% advantage for once-daily dosing, which was also not statistically significant (P = .41).
Overall, there was an average increase of 2.5% in rates of adherence for those taking once-daily regimens versus twice-daily regimens, a modest but statistically significant difference. By comparison, there was an average increase of about 1% in rates of virologic suppression for those taking once-daily regimens versus twice-daily regimens -- however, this difference was not statistically significant.
The researchers noted that the relatively small increase in adherence rates may have contributed to this apparent lack of virologic outcome. However, they also noted limitations that may have been a factor, including possible pharmacokinetic differences between the drugs in once-daily regimens versus twice-daily regimens, the short duration of several of the trials and the recruitment (in some trials) of treatment-experienced patients who were likely already highly adherent and virologically suppressed. For these reasons, the researchers believe the difference in rates of virologic suppression may be underestimated.
Nachega also stated that when analyzing all studies and patient groups cumulatively, the higher the number of pills -- or "pill burden" -- in a regimen, the lower the rates of adherence and virologic suppression were among patients.
Given all of these results, the researchers concluded that switching patients from a once-daily regimen to a twice-daily regimen may be reasonable, particularly if they are experiencing side effects on their once-daily regimen. However, the wisdom behind any switch may greatly depend on the number of pills in the regimen, they warned, as pill burden was found to be a predictor of treatment success.
Further study is warranted, in particular to investigate the impact of switching from a once-daily single-tablet regimen to a once-daily multi-tablet regimen.