Background: The monitoring of nevirapine (NVP) concentrations in pediatric patients has gained interest since the introduction of NVP as part of the preferred first-line antiretroviral regimen for human immunodeficiency virus (HIV)-infected children in resource-limited settings. Adequate trough concentrations of NVP predict successful therapy, whereas subtherapeutic levels are correlated with virologic failure and development of resistance. The aim of this study was to determine the extent of agreement between total and free plasma NVP concentrations and nonstimulated saliva NVP concentrations and to evaluate the feasibility of saliva sampling as an alternative tool for therapeutic drug monitoring of NVP in children.
Design and Methods: The study was designed as an observational cohort analysis. NVP concentrations were obtained in paired plasma and saliva samples of pediatric patients receiving antiretroviral therapy, including NVP. NVP plasma and saliva concentrations were determined by a tandem-mass spectrometric method. The intraclass correlation coefficient and Bland-Altman analysis were used to evaluate agreement and to assess pattern in any discrepancies between measurements.
Results: For the random paired plasma and saliva NVP sampling, 19 African-American children (8 boys, 11 girls) with a median age of 8.0 years were enrolled. Two male subjects were recruited for the 12 hour NVP plasma and saliva pharmacokinetics study. The intraclass correlations between saliva and serum measurements of NVP concentrations indicated >90% agreement between these two modes of measurement. The saliva concentrations reflected the free concentrations very closely but were on average 34% higher. The Bland-Altman plots indicated that the discrepancy between saliva and plasma measures is consistent across the range of average NVP concentrations.
Conclusions: Our study results strongly indicate agreement between saliva and plasma NVP concentrations in pediatric patients with HIV infection, on the basis of Bland-Altman analysis. Nonstimulated NVP saliva concentrations can be used as an alternative noninvasive, reliable, cost-effective method for direct measurement of adherence and application of therapeutic drug monitoring in NVP therapy.
From the *Division of Infectious Disease; †Division of Pediatric Clinical Pharmacology; Departments of ‡Laboratory Medicine; §Pediatrics; ¶Pathology; ‖Pharmacology; and #Microbiology, Immunology and Tropical Medicine, The George Washington University School of Medicine, Washington, DC; **Department of Pharmacology, Georgetown University and Georgetown Clinical Research Center, Washington, DC; ††Division of Pediatric Clinical Pharmacology and Developmental Therapeutics, Department of Pediatrics; ‡‡Skaggs School of Pharmacy, University of California San Diego, La Jolla, California.
Received for publication June 26, 2006; accepted December 12, 2006.
Grant support: This work was supported by the Department of Health and Human Services, NIH, PHS (grants NCRR 1K12 RR017613, MO1-RR-020359 and NICHD 1U10 HD45993).
Correspondence: Natella Rakhmanina, MD, Assistant Professor of Pediatrics, The George Washington University, Clinic Director, Special Immunology/Infectious Diseases, Children's National Medical Center, 111 Michigan Avenue NW, Washington, DC 20010 (e-mail: email@example.com).