Lower pill burden and once-daily antiretroviral treatment regimens for HIV infection: A meta-analysis of randomized controlled trials

Abstract

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.

Keywords: ART; fixed-dose combination; once-daily; randomized controlled trials; twice-daily.

Figure 1.

Study selection flow diagram. Abbreviations: QD, once daily; RCT, randomized controlled trial; TID, three times a day.

Figure 2.

Antiretroviral therapy adherence rate, virological response, and pill burden. Area of circle is proportional to the sample size. Blue, once-daily regimens; orange, twice-daily regimens.

Figure 3.

Forest plot of the effect of once-daily vs twice-daily antiretroviral regimens on the rate of adherence. Abbreviations: CI, confidence interval; IV, inverse variance; SD, standard deviation.

Figure 4.

Forest plot of the effect of once-daily vs twice-daily antiretroviral regimens on virologic suppression (plasma RNA HIV level <50 or <200 copies/mL). Abbreviations: CI, confidence interval; HIV, human immunodeficiency virus; M-H, Mantel-Haenszel.