Kouanfack C, Laurent C, Peytavin G, Ciaffi L, Ngolle M, Mawamba Y, et al. Adherence to antiretroviral therapy assessed by drug level monitoring and self-report in Cameroon. J Acquir Immune Defic Syndr 2008;48:216-19.
Adherence to antiretroviral therapy (ART) is essential for optimal response and to reduce the development of ART resistance.(1,2,3) Although several methods to measure adherence have been assessed in sub-Saharan Africa, self-report is the most frequently used despite its associated recall and social desirability biases.(4) Measurement of adherence through drug level monitoring has not been widely assessed in this region.
To compare adherence to a fixed dose combination (FDC) of nevirapine, stavudine, and lamivudine using nevirapine plasma level monitoring and patient self-report and to examine the relation between these two methods and viral load measurements
Cohort analysis of data obtained from a clinical trial of FDC of ART efficacy, safety, and quality
Forty-eight patients who were enrolled in the clinical trial who received the FDC during the study period in which adherence and viral load measurements were collected
Self-reported and plasma level measurements of adherence, the association between these two adherence measures and plasma viral load, and the sensitivity, specificity, and positive and negative predictive values of the two measures of adherence
Patients were enrolled in the clinical trial between November 2002 and April 2003. Patients were followed at the clinic every month for the first year and then every 2-3 months thereafter. Patients completed an interview and physical examination at each visit. The patients were asked about the number of ART doses that were missed in the previous 7 days. Self-reported adherence was calculated as the ratio of the number of reported doses to the number of prescribed doses. Nevirapine minimum plasma concentration was measured 12 hours after the last dose every 6 months. Adequate adherence was defined as a nevirapine plasma concentration of at least 4000 ng/ml (the threshold of efficacy). Viral load measurements were obtained every 6 months using a test with the sensitivity to detect as few as 50 copies/mL.
The 48 patients provided 159 complete observations between months 12 and 36. Nevirapine concentrations of at least 4000 ng/ml were present in 88.7% of participants. Concentrations of less than 4000 ng/ml were associated with virologic failure.(5) Using the virologic outcome as comparison, the sensitivity of the nevirapine level monitoring of inadequate adherence was 20.5%, the specificity was 91.7%, the positive predictive value was 44.4% and the negative predictive value was 78.0%. Self-reported adherence was over 95% in 155 observations, 92.9% in two observations, 85.75 in one observation, and zero in one patient who was traveling. The self-reported adherence was significantly higher than adherence measured by the nevirapine level monitoring (P=0.002). Self-reported adherence was not associated with virologic failure. Compared with virologic outcome, the sensitivity of self-report to predict inadequate adherence was 2.6%, the specificity was 97.5%, the positive predictive value was 25.0%, and the negative predictive value was 75.5%.
Nevirapine plasma concentration monitoring provides a more accurate measurement of adherence than does self-report. Drug level monitoring is not practical as an ongoing practice in clinical settings in resource-constrained areas, which highlights the need for methods to increase the accuracy of self-reported adherence.
This is a good analysis of data collected during a clinical ART trial. Representativeness of subjects could not be assessed. Methods of adherence measurements were very good, and definitions were clearly stated and applied to all participants. Use of nevirapine plasma concentration provided an outstanding comparison standard to use against self-report.
This study provides additional information highlighting the poor sensitivity of self-report as a measure of adherence. Although plasma concentration measurement of ART is a more sensitive measure of adherence, its routine application is not practical. Additional methods of monitoring adherence that are inexpensive and sensitive should be evaluated and implemented. Methods to improve self-reported adherence are needed because this measure is likely to continue to be the most widely used in clinical practice in such settings.
- Mannheimer S, Friedland G, Matts J, et al. The consistency of adherence to antiretroviral therapy predicts biologic outcomes for human immunodeficiency virus-infected persons in clinical trials. Clin Infect Dis 2002;34:1115-21.
- Sethi AK, Celentano DD, Gange SJ, et al. Association between adherence to antiretroviral therapy and human immunodeficiency virus drug resistance. Clin Infect Dis 2003;37:1112-18.
- Wainberg MA, Friedland G. Public health implications of antiretroviral therapy and HIV drug resistance. JAMA 1998;279:1977-83.
- Mills EJ, Nachega JB, Buchan I, et al. Adherence to antiretroviral therapy in sub-Saharan Africa and North America: a meta-analysis. JAMA 2006;296:679-90.
- Murphy R, Montaner J. Nevirapine: a review of its development, pharmacological profile and potential for clinical use. Expert Opin Investig Drugs 1996;5:1183-99.