Effect of adherence to newly initiated antiretroviral therapy on plasma viral load

ObjectiveTo determine whether differences in adherence to newly initiated antiretroviral therapy exist between subjects who do and do not achieve undetectable plasma viral loads. DesignObservational cohort study monitoring adherence and virological and immunological parameters over the initial 4 months of therapy with nelfinavir. Adherence was measured using the microelectronic monitoring system (MEMS; APREX Corporation, Menlo Park, California, USA). SettingGeneral Clinical Research Center at a tertiary care center. ParticipantsForty-one protease inhibitor-naive subjects with viral loads > 10 000 copies/ml newly starting a regimen including nelfinavir, referred from HIV clinics in Philadelphia. Main outcome measuresThe primary outcome was undetectable viral load (< 50 copies/ml) after 4 months. Secondary measures included changes in viral load and CD4 cell counts. We hypothesized that adherence would be greater in subjects who achieved undetectable viral loads. ResultsAdherence was greater in undetectable subjects, who took a median of 93% of prescribed doses [interquartile range (IQR) 84–96%], whereas detectable subjects took a median of 70% (IQR 46–93%). Adherence correlated with viral load decrease (Spearman's ρ = 0.38, P < 0.01) and CD4 cell count increase (Spearman's ρ = 0.25, P = 0.06). Despite differences between the groups over 4 months of therapy, there were no adherence differences over the first month [undetectables, 95% (IQR 88–98%) versus detectables, 94% (IQR 87–98%), P > 0.50]. ConclusionsAdherence is important in determining whether or not individuals achieve suppression with a newly initiated antiretroviral regimen. Adherence begins to wane after the first month of therapy. Therefore, closer assessment of adherence particularly after this first month is important.

[1]  Susan Swindells,et al.  Adherence to Protease Inhibitor Therapy and Outcomes in Patients with HIV Infection , 2000, Annals of Internal Medicine.

[2]  A. Wu,et al.  Self-reported adherence to antiretroviral medications among participants in HIV clinical trials: The AACTG Adherence Instruments , 2000, AIDS care.

[3]  D. Richman,et al.  Predictors of Self‐Reported Adherence and Plasma HIV Concentrations in Patients on Multidrug Antiretroviral Regimens , 2000, Journal of acquired immune deficiency syndromes.

[4]  F. Hecht,et al.  Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent population , 2000, AIDS.

[5]  Laura M. Bogart,et al.  Patterns, correlates, and barriers to medication adherence among persons prescribed new treatments for HIV disease. , 2000, Health psychology : official journal of the Division of Health Psychology, American Psychological Association.

[6]  M A Fischl,et al.  Antiretroviral Therapy in Adults Updated Recommendations of the International AIDS Society–USA Panel , 2000 .

[7]  V. Calvez,et al.  Mechanisms of virologic failure in previously untreated HIV-infected patients from a trial of induction-maintenance therapy. Trilège (Agence Nationale de Recherches sur le SIDA 072) Study Team). , 2000, JAMA.

[8]  R. Chaisson,et al.  Highly Active Antiretroviral Therapy in a Large Urban Clinic: Risk Factors for Virologic Failure and Adverse Drug Reactions , 1999, Annals of Internal Medicine.

[9]  D Johnson,et al.  The value of patient-reported adherence to antiretroviral therapy in predicting virologic and immunologic response. California Collaborative Treatment Group. , 1999, AIDS.

[10]  Richard A. Loftus,et al.  HIV RNA and CD4 cell count response to protease inhibitor therapy in an urban AIDS clinic: response to both initial and salvage therapy. , 1999, AIDS.

[11]  A Nicoll,et al.  Selective versus universal antenatal HIV testing: epidemiological and implementational factors in policy choice. , 1999, AIDS.

[12]  S. Hammer,et al.  Antiretroviral therapy for HIV infection in 1997. Updated recommendations of the International AIDS Society-USA panel. , 1998, JAMA.

[13]  B Clotet,et al.  Antiretroviral drug resistance testing in adults with HIV infection: implications for clinical management. International AIDS Society--USA Panel. , 1998, JAMA.

[14]  M. Wainberg,et al.  Public health implications of antiretroviral therapy and HIV drug resistance. , 1998, JAMA.

[15]  B Vrijens,et al.  Comparing compliance patterns between randomized treatments. , 1997, Controlled clinical trials.

[16]  Alan S. Perelson,et al.  Decay characteristics of HIV-1-infected compartments during combination therapy , 1997, Nature.

[17]  J R Ickovics,et al.  Adherence in AIDS clinical trials: a framework for clinical research and clinical care. , 1997, Journal of clinical epidemiology.

[18]  T F Blaschke,et al.  Patient compliance and drug failure in protease inhibitor monotherapy. , 1996, JAMA.

[19]  R. Straka,et al.  Magnitude and Nature of Noncompliance with Treatment using Isosorbide Dinitrate in Patients with Ischemic Heart Disease , 1996, Journal of clinical pharmacology.

[20]  C Desforges,et al.  Dose Frequency and Dose Interval Compliance with Multiple Antiepileptic Medications During a Controlled Clinical Trial , 1995, Epilepsia.

[21]  T. Wall,et al.  Adherence to zidovudine (AZT) among HIV-infected methadone patients: a pilot study of supervised therapy and dispensing compared to usual care. , 1995, Drug and alcohol dependence.

[22]  J. Brun Patient Compliance with Once-Daily and Twice-daily Oral Formulations of 5-Isosorbide Mononitrate: A Comparative Study , 1994, The Journal of international medical research.

[23]  G Koren,et al.  Critical Comparison of Novel and Existing Methods of Compliance Assessment During a Clinical Trial of an Oral Iron Chelator , 1994, Journal of clinical pharmacology.

[24]  G E Dallal,et al.  LMSMVE: a program for least median of squares regression and robust distances. , 1992, Computers and biomedical research, an international journal.

[25]  G Koren,et al.  Compliance assessed by the Medication Event Monitoring System. , 1991, Archives of disease in childhood.

[26]  J. Hanley,et al.  A method of comparing the areas under receiver operating characteristic curves derived from the same cases. , 1983, Radiology.

[27]  S Greenland,et al.  Tests for interaction in epidemiologic studies: a review and a study of power. , 1983, Statistics in medicine.

[28]  J. Hanley,et al.  The meaning and use of the area under a receiver operating characteristic (ROC) curve. , 1982, Radiology.

[29]  J. Rabkin,et al.  Adherence: a necessity for successful HIV combination therapy. , 1999, AIDS.

[30]  W. Bilker,et al.  Potential utility of electronic drug compliance monitoring in measures of adverse outcomes associated with immunosuppressive agents , 1999, Pharmacoepidemiology and drug safety.

[31]  B. Walker,et al.  Report of the NIH Panel To Define Principles of Therapy of HIV Infection* , 1998, Annals of Internal Medicine.

[32]  W. Dupont,et al.  Power and sample size calculations. A review and computer program. , 1990, Controlled clinical trials.