Meta-analysis Finds Better Adherence with Once-Daily Antiretroviral Regimens

By Liz Highleyman

Antiretroviral therapy is much more convenient than it was in the early days of combination HAART, with lower "pill burdens," fewer food restrictions, and less frequent administration. While some early regimens required handfuls of pills taken 3 times a day, the simplest current regimen consists of 1 pill, once daily.

But while once-daily regimens are simpler than those taken 2or 3 times daily, it has not been established whether they are associated with better adherence, which has been shown to reduce the likelihood of virological failure, disease progression, and death.

As described in the February 15, 2009 issue of Clinical Infectious Diseases, Jean-Jacques Parienti and colleagues performed a meta-analysis of randomized trials addressing this question.

Results

The researchers identified 11 randomized, controlled trials with a combined total of 3029 study participants.

The adherence rate was significantly better with once-daily regimens compared with twice-daily regimens (+2.9%; P < 0.003).

This modest effect was more pronounced at the time of treatment initiation, and for regimens in which all medications were taken once-daily.

In their discussion, the study authors suggested that, "The smaller effect among recipients of stable treatment may be related to selection bias toward more highly adherent patients in these studies, because all studies required an undetectable viral load before enrollment."

"Although it was statistically significant, the 2.9% difference in adherence between once-daily and twice-daily regimens was modest," they noted. "This difference in adherence did not correspond to an overall difference in rates of viral suppression among all studies. However, similar to the primary analysis of adherence, there was a difference in the rates of viral suppression that favored studies involving antiretroviral-naive patients over switch studies."

"Antiretroviral-naive patients may be more sensitive to differences in adherence because of lower rates of preexisting drug resistance," they continued. "Furthermore, the association between adherence and viral suppression is likely to be more critical when rates of viral replication are high, such as at the time of initiation of a first antiretroviral regimen."

"Because adherence to medication regimens is a complex behavior with multiple factors at play, efforts to improve adherence should not be restricted to prescription of once-daily medications," the authors recommended. "Other factors, including tolerability, potency, and potential risk of resistance, given the patient's individual adherence pattern, are important considerations in selecting the optimal regimen for each patient."

Departments of Biostatistics and Clinical Research and Infectious Diseases, Cote de Nacre University Hospital, Caen, France; Pierre et Marie Curie University and 4INSERM U707, Paris, France; Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA; Public Health Department, Denver Health and Hospital Authority, Denver, CO.

2/03/09

Reference
JJ Parienti, DR Bangsberg, R Verdon, and EM Gardner. Better Adherence with Once-Daily Antiretroviral Regimens: A Meta-Analysis. Clinical Infectious Diseases 48(4): 484-488. February 15, 2009. (Abstract).