Lower pill burden and once-daily antiretroviral treatment regimens for HIV infection: A meta-analysis of randomized controlled trials.
BACKGROUND
Contemporary antiretroviral treatment regimens are simpler than in the past, with lower pill burden and once-daily dosing frequency common. We performed a meta-analysis of randomized controlled trials (RCTs) to investigate the impact of pill burden and once-daily vs twice-daily dosing on ART adherence and virological outcomes.


METHODS
A literature search of 4 electronic databases through 31 March 2013 was used. RCTs comparing once-daily vs twice-daily ART regimens that also reported on adherence and virological suppression were included. Study design, study population characteristics, intervention, outcome measures, and study quality were extracted. Study quality was rated using the Cochrane risk-of-bias tool.


RESULTS
Nineteen studies met our inclusion criteria (N = 6312 adult patients). Higher pill burden was associated with both lower adherence rates (P = .004) and worse virological suppression (P < .0001) in both once-daily and twice-daily subgroups, although the association with adherence in the once-daily subgroup was not statistically significant. The average adherence was modestly higher in once-daily regimens than twice-daily regimens (weighted mean difference = 2.55%; 95% confidence interval [CI], 1.23 to 3.87; P = .0002). Patients on once-daily regimens did not achieve virological suppression more frequently than patients on twice-daily regimens (relative risk [RR] = 1.01; 95% CI, 0.99 to 1.03; P = .50). Both adherence and viral load suppression decreased over time, but adherence decreased less with once-daily dosing than with twice-daily dosing.


CONCLUSIONS
Lower pill burden was associated with both better adherence and virological suppression. Adherence, but not virological suppression, was slightly better with once- vs twice-daily regimens.
Department of Epidemiology, Pittsburgh University Graduate School of Public Health, Pennsylvania.
Jean B
JB
Nachega
Jean-Jacques
JJ
Parienti
Olalekan A
OA
Uthman
Robert
R
Gross
David W
DW
Dowdy
Paul E
PE
Sax
Joel E
JE
Gallant
Michael J
MJ
Mugavero
Edward J
EJ
Mills
Thomas P
TP
Giordano
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D010349:Patient Compliance; D016032:Randomized Controlled Trials as Topic; D019562:Viral Load
D019380:Anti-HIV Agents
ART; fixed-dose combination; once-daily; randomized controlled trials; twice-daily