The Effect on Treatment Adherence of Administering Drugs As Fixed-Dose Combinations Versus As Separate Pills: Systematic Review and Meta-Analysis

Overview

Journal AIDS Res Treat

Publisher Wiley

Specialty Infectious Diseases

Date 2014 Oct 3

PMID 25276422

Citations 18

Authors

Katy A van Galen

Jeannine F Nellen

Pythia T Nieuwkerk

Affiliations

Soon will be listed here.

Abstract

Administering drugs as fixed-dose combinations (FDCs) versus the same active drugs administered as separate pills is assumed to enhance treatment adherence. We synthesized evidence from randomized controlled trials (RCTs) about the effect of FDCs versus separate pills on adherence. We searched PubMed for RCTs comparing a FDC with the same active drugs administered as separate pills, including a quantitative estimate of treatment adherence, without restriction to medical condition. The odds ratio (OR) of optimal adherence with FDCs versus separate pills was used as common effect size and aggregated into a pooled effect estimate using a random effect model with inverse variance weights. Out of 1258 articles screened, only six studies fulfilled inclusion criteria. Across medical conditions, administering drugs as FDC significantly increased the likelihood of optimal adherence (OR 1.33 (95% CI, 1.03-1.71)). Within subgroups of specific medical conditions, the favourable effect of FDCs on adherence was of borderline statistical significance for HIV infection only (OR 1.46 (95% CI, 1.00-2.13)). We observed a remarkable paucity of RCTs comparing the effect on adherence of administering drugs as FDC versus as separate pills. Administering drugs as FDC improved medication adherence. However, this conclusion is based on a limited number of RCTs only.

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References

Nachega J, Parienti J, Uthman O, Gross R, Dowdy D, Sax P . Lower pill burden and once-daily antiretroviral treatment regimens for HIV infection: A meta-analysis of randomized controlled trials. Clin Infect Dis. 2014; 58(9):1297-307. PMC: 3982838. DOI: 10.1093/cid/ciu046. View

Geiter L, OBrien R, Combs D, Snider Jr D . United States Public Health Service Tuberculosis Therapy Trial 21: preliminary results of an evaluation of a combination tablet of isoniazid, rifampin and pyrazinamide. Tubercle. 1987; 68(2 Suppl):41-6. DOI: 10.1016/0041-3879(87)90021-3. View

Eron J, Yetzer E, Ruane P, Becker S, Sawyer G, Fisher R . Efficacy, safety, and adherence with a twice-daily combination lamivudine/zidovudine tablet formulation, plus a protease inhibitor, in HIV infection. AIDS. 2000; 14(6):671-81. DOI: 10.1097/00002030-200004140-00006. View

Airoldi M, Zaccarelli M, Bisi L, Bini T, Antinori A, Mussini C . One-pill once-a-day HAART: a simplification strategy that improves adherence and quality of life of HIV-infected subjects. Patient Prefer Adherence. 2010; 4:115-25. PMC: 2875721. DOI: 10.2147/ppa.s10330. View

ASPLUND J, Danielson M, Ohman P . Patients compliance in hypertension--the importance of number of tablets. Br J Clin Pharmacol. 1984; 17(5):547-52. PMC: 1463452. DOI: 10.1111/j.1365-2125.1984.tb02388.x. View

Nachega J, Mugavero M, Zeier M, Vitoria M, Gallant J . Treatment simplification in HIV-infected adults as a strategy to prevent toxicity, improve adherence, quality of life and decrease healthcare costs. Patient Prefer Adherence. 2011; 5:357-67. PMC: 3150164. DOI: 10.2147/PPA.S22771. View

Bangalore S, Kamalakkannan G, Parkar S, Messerli F . Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med. 2007; 120(8):713-9. DOI: 10.1016/j.amjmed.2006.08.033. View

Su W, Perng R . Fixed-dose combination chemotherapy (Rifater/Rifinah) for active pulmonary tuberculosis in Taiwan: a two-year follow-up. Int J Tuberc Lung Dis. 2002; 6(11):1029-32. View

Lazo M, Gange S, Wilson T, Anastos K, Ostrow D, Witt M . Patterns and predictors of changes in adherence to highly active antiretroviral therapy: longitudinal study of men and women. Clin Infect Dis. 2007; 45(10):1377-85. DOI: 10.1086/522762. View

10.

Ioannidis J, Haidich A, Pappa M, Pantazis N, Kokori S, Tektonidou M . Comparison of evidence of treatment effects in randomized and nonrandomized studies. JAMA. 2001; 286(7):821-30. DOI: 10.1001/jama.286.7.821. View

11.

Glass T, Battegay M, Cavassini M, de Geest S, Furrer H, Vernazza P . Longitudinal analysis of patterns and predictors of changes in self-reported adherence to antiretroviral therapy: Swiss HIV Cohort Study. J Acquir Immune Defic Syndr. 2009; 54(2):197-203. DOI: 10.1097/QAI.0b013e3181ca48bf. View

12.

Ammassari A, Trotta M, Murri R, Castelli F, Narciso P, Noto P . Correlates and predictors of adherence to highly active antiretroviral therapy: overview of published literature. J Acquir Immune Defic Syndr. 2003; 31 Suppl 3:S123-7. DOI: 10.1097/00126334-200212153-00007. View

13.

Bartlett J, DeMasi R, Quinn J, Moxham C, Rousseau F . Overview of the effectiveness of triple combination therapy in antiretroviral-naive HIV-1 infected adults. AIDS. 2001; 15(11):1369-77. DOI: 10.1097/00002030-200107270-00006. View

14.

Buscher A, Hartman C, Kallen M, Giordano T . Impact of antiretroviral dosing frequency and pill burden on adherence among newly diagnosed, antiretroviral-naive HIV patients. Int J STD AIDS. 2012; 23(5):351-5. PMC: 3642979. DOI: 10.1258/ijsa.2011.011292. View

15.

Gazzard B, Moecklinghoff C, Hill A . New strategies for lowering the costs of antiretroviral treatment and care for people with HIV/AIDS in the United Kingdom. Clinicoecon Outcomes Res. 2012; 4:193-200. PMC: 3414377. DOI: 10.2147/CEOR.S12496. View

16.

Cohen C, Meyers J, Davis K . Association between daily antiretroviral pill burden and treatment adherence, hospitalisation risk, and other healthcare utilisation and costs in a US medicaid population with HIV. BMJ Open. 2013; 3(8). PMC: 3733306. DOI: 10.1136/bmjopen-2013-003028. View

17.

Protopopescu C, Raffi F, Roux P, Reynes J, Dellamonica P, Spire B . Factors associated with non-adherence to long-term highly active antiretroviral therapy: a 10 year follow-up analysis with correction for the bias induced by missing data. J Antimicrob Chemother. 2009; 64(3):599-606. DOI: 10.1093/jac/dkp232. View

18.

Sosa N, Hill-Zabala C, DeJesus E, Herrera G, Florance A, Watson M . Abacavir and lamivudine fixed-dose combination tablet once daily compared with abacavir and lamivudine twice daily in HIV-infected patients over 48 weeks (ESS30008, SEAL). J Acquir Immune Defic Syndr. 2005; 40(4):422-7. DOI: 10.1097/01.qai.0000184859.24071.bd. View

19.

Stoll M, Kollan C, Bergmann F, Bogner J, Faetkenheuer G, Fritzsche C . Calculation of direct antiretroviral treatment costs and potential cost savings by using generics in the German HIV ClinSurv cohort. PLoS One. 2011; 6(9):e23946. PMC: 3170283. DOI: 10.1371/journal.pone.0023946. View

20.

Mannheimer S, Friedland G, Matts J, Child C, Chesney M . The consistency of adherence to antiretroviral therapy predicts biologic outcomes for human immunodeficiency virus-infected persons in clinical trials. Clin Infect Dis. 2002; 34(8):1115-21. DOI: 10.1086/339074. View